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Zheng W, Wang F, Tao N, Wang X, Jin X, Zhang C, Xu C. An androgenetic alopecia remedy based on marine collagen peptide-incorporated dissolving microneedles. Int J Pharm 2024; 650:123629. [PMID: 37992979 DOI: 10.1016/j.ijpharm.2023.123629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/09/2023] [Accepted: 11/19/2023] [Indexed: 11/24/2023]
Abstract
Given that current androgenetic alopecia (AGA) medications have adverse effects such as sexual dysfunction and drug dependence, researchers are actively exploring natural bioactive ingredients and innovative approaches (e.g., transdermal drug delivery systems) to effectively combat hair loss with minimal side effects. Herein, we develop a new transdermal drug delivery system incorporating globefish skin collagen peptides with dissolving microneedles (GSCPs-MNs) for hair regrowth. These microneedles generate skin micro-wounds upon application, which not only improves the efficiency of bioactive ingredients delivery, but also stimulates signals involved in hair follicle (HF) regeneration. Our in vivo study shows that minimally invasive implanted GSCPs-MNs are more effective than topical GSCPs in reducing inflammation and promoting collagen formation. Additionally, the upregulation of vascular markers including VEGF and CD31 alongside the downregulation of TNF-α, IL-1β, and malondialdehyde (MDA) index indicate that GSCPs-MNs can significantly alleviate inflammation and oxidation, as well as promoting vascularization and HF functionalization. Overall, our findings suggest that GSCPs-MNs can effectively promote hair regrowth in AGA mice, which offer excellent prospects for the development of new therapeutics and cosmetic supplements for hair loss, along with the combined drug delivery optimization, which could alleviate hair loss in patients with AGA.
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Affiliation(s)
- Wei Zheng
- College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China; Suzhou Qinpu Biotechnology Pte Ltd, Suzhou, Jiangsu Province 215215, China
| | - Fan Wang
- College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China; School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China; Suzhou Qinpu Biotechnology Pte Ltd, Suzhou, Jiangsu Province 215215, China
| | - Ningping Tao
- College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China; Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China; Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation, Ministry of Agriculture, Shanghai 201306, China; National R & D Branch Center for Freshwater Aquatic Products Processing Technology, Shanghai 201306, China
| | - Xichang Wang
- College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China; Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China; Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation, Ministry of Agriculture, Shanghai 201306, China; National R & D Branch Center for Freshwater Aquatic Products Processing Technology, Shanghai 201306, China
| | - Xin Jin
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.
| | - Chuan Zhang
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.
| | - Changhua Xu
- College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, China; Shanghai Engineering Research Center of Aquatic-Product Processing & Preservation, Shanghai 201306, China; Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation, Ministry of Agriculture, Shanghai 201306, China; National R & D Branch Center for Freshwater Aquatic Products Processing Technology, Shanghai 201306, China.
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Lee KH, Kim JD, Jeong DH, Kim SM, Park CO, Lee KH. Development of a novel microneedle platform for biomarker assessment of atopic dermatitis patients. Skin Res Technol 2023; 29:e13413. [PMID: 37522507 PMCID: PMC10345975 DOI: 10.1111/srt.13413] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 07/04/2023] [Indexed: 08/01/2023]
Abstract
BACKGROUND Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis, cause, and treatment have been extensively studied. The association of AD with Th2 cytokines is well known; therefore, the analysis of this association is crucial for the diagnosis and treatment of AD. This study aimed to present a new method for measuring protein biomarkers in patients with AD, before and after treatment, using minimally invasive microneedles. MATERIALS AND METHODS First, hyaluronic acid-loaded microneedle patches (HA-MNs) for skin sample collection were fabricated. Next, after Institutional Review Board approval, 20 patients with AD were recruited and skin samples were taken before and after treatment using four different sampling techniques: (1) tape stripping, (2) hydrocolloid patches, (3) hollow microneedles, and (4) HA-MNs. Lastly, proteins were isolated from the collected samples, and AD-related biomarkers were analyzed by enzyme-linked immunosorbent assay. RESULTS Proteins were successfully extracted from the skin samples collected by tape stripping, hydrocolloid patches, and HA-MNs, except hollow microneedles. Interleukin (IL)-4, IL-13, and interferon-γ were detected in the HA-MNs only. By comparing the biomarker level correlation before and after treatment and the improvement score of the patients, we observed a significant negative correlation between IL-4 and IL-13 with an improvement in AD symptoms. CONCLUSION Overall, our results verified that HA-MNs can be used to effectively analyze protein levels of biomarkers from skin metabolites of patients with AD and can be applied to monitor the treatment progress of patients with AD in a minimally invasive manner.
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Affiliation(s)
| | | | | | - Su Min Kim
- Department of Dermatology and Cutaneous Biology Research InstituteSeverance HospitalYonsei University College of MedicineSeoulRepublic of Korea
| | - Chang Ook Park
- Department of Dermatology and Cutaneous Biology Research InstituteSeverance HospitalYonsei University College of MedicineSeoulRepublic of Korea
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3D Printed Hollow Microneedles for Treating Skin Wrinkles Using Different Anti-Wrinkle Agents: A Possible Futuristic Approach. COSMETICS 2023. [DOI: 10.3390/cosmetics10020041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023] Open
Abstract
Skin wrinkles are an inevitable phenomenon that is brought about by aging due to the degradation of scleroprotein fibers and significant collagen reduction, which is the fundamental basis of anti-wrinkle technology in use today. Conventional treatments such as lasering and Botulinum toxin have some drawbacks including allergic skin reactions, cumbersome treatment procedures, and inefficient penetration of the anti-wrinkle products into the skin due to the high resistance of stratum corneum. Bearing this in mind, the cosmetic industry has exploited the patient-compliant technology of microneedles (MNs) to treat skin wrinkles, developing several products based on solid and dissolvable MNs incorporated with antiwrinkle formulations. However, drug administration via these MNs is limited by the high molecular weight of the drugs. Hollow MNs (HMNs) can deliver a wider array of active agents, but that is a relatively unexplored area in the context of antiwrinkle technology. To address this gap, we discuss the possibility of bioinspired 3D printed HMNs in treating skin wrinkles in this paper. We compare the previous and current anti-wrinkling treatment options, as well as the techniques and challenges involved with its manufacture and commercialization.
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Size matters: differential property of hyaluronan and its fragments in the skin- relation to pharmacokinetics, immune activity and wound healing. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2023. [DOI: 10.1007/s40005-023-00614-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
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Xing M, Liu H, Meng F, Ma Y, Zhang S, Gao Y. Design and Evaluation of Complex Polypeptide-Loaded Dissolving Microneedles for Improving Facial Wrinkles in Different Areas. Polymers (Basel) 2022; 14:polym14214475. [PMID: 36365468 PMCID: PMC9653557 DOI: 10.3390/polym14214475] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/14/2022] [Accepted: 10/19/2022] [Indexed: 11/05/2022] Open
Abstract
Wrinkles are one of the most intuitive manifestations of skin aging. Complex polypeptide-loaded dissolving microneedles (CP-DMNs) for facial wrinkles in different areas have been developed and evaluated for the first time. In optimizing formulations, we compared the differences in CP-DMNs heights on skin insertion depth and skin repair and healing. Furthermore, systemic safety experiments were carried out to provide a reference for clinical application. On this basis, an 84-day efficacy assessment based on the improvement of facial wrinkles in different areas and a comparison between CP-DMNs vs. placebo was performed on 30 healthy subjects. As a result, DMNs with a height of 300 μm presented sufficient strength to pierce the stratum corneum with minimized skin damage. In addition, CP-DMNs possessed excellent biological safety and skin compatibility for clinical application. Compared with placebo, CP-DMNs exhibited obvious improvements in wrinkles distributed in the corners of eyes, under-eyes, and nasolabial folds. Furthermore, after using CP-DMNs for 84 days, facial wrinkles in five different areas were smoothed. In short, the complex polypeptides showed apparent anti-wrinkle efficacy with the aid of DMNs technology, and CP-DMNs seemed to work better on deeper wrinkles, such as frown lines and nasolabial folds.
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Affiliation(s)
- Mengzhen Xing
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- Key Laboratory of New Material Research Institute, Department of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Han Liu
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- Technical Institute of Physics and Chemistry, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Fanda Meng
- School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China
| | - Yuning Ma
- Key Laboratory of New Material Research Institute, Department of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Suohui Zhang
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- Beijing CAS Microneedle Technology Ltd., Beijing 102609, China
- Correspondence: (S.Z.); (Y.G.); Tel.: +86-010-8254-3582 (S.Z.); +86-010-8254-3581 (Y.G.)
| | - Yunhua Gao
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- Technical Institute of Physics and Chemistry, University of Chinese Academy of Sciences, Beijing 100049, China
- Beijing CAS Microneedle Technology Ltd., Beijing 102609, China
- Correspondence: (S.Z.); (Y.G.); Tel.: +86-010-8254-3582 (S.Z.); +86-010-8254-3581 (Y.G.)
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NupR Responding to Multiple Signals Is a Nucleoside Permease Regulator in Bacillus thuringiensis BMB171. Microbiol Spectr 2022; 10:e0154322. [PMID: 35862946 PMCID: PMC9430930 DOI: 10.1128/spectrum.01543-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Nucleoside transport is essential for maintaining intracellular nucleoside and nucleobase homeostasis for living cells. Here, we identified an uncharacterized GntR/HutC family transcriptional regulator, NagR2, renamed NupR (nucleoside permease regulator), that mainly controls nucleoside transport in the Bacillus thuringiensis BMB171 strain. The deletion or overexpression of nupR affected the bacteria's utilization of guanosine, adenosine, uridine, and cytidine rather than thymidine. We further demonstrated that zinc ion is an effector for the NupR, dissociating NupR from its target DNA. Moreover, the expression of nupR is inhibited by NupR, ComK, and PurR, while it is promoted by CcpA. Also, a purine riboswitch located in its 5′ noncoding region influences the expression of nupR. Guanine is the ligand of the riboswitch, reducing the expression of nupR by terminating the transcription of nupR in advance. Hence, our results reveal an exquisite regulation mechanism enabling NupR to respond to multiple signals, control genes involved in nucleoside transport, and contribute to nucleoside substance utilization. Overall, this study provides essential clues for future studies exploring the function of the NupR homolog in other bacteria, such as Bacillus cereus, Bacillus anthracis, Klebsiella pneumoniae, and Streptococcus pneumoniae. IMPORTANCE The transport of nucleosides and their homeostasis within the cell are essential for growth and proliferation. Here, we have identified a novel transcription factor, NupR, which, to our knowledge, is the first GntR family transcription factor primarily involved in the regulation of nucleoside transport. Moreover, responding to diverse intracellular signals, NupR regulates nucleoside transport. It is vital for utilizing extracellular nucleosides and maintaining intracellular nucleoside homeostasis. NupR may also be involved in other pathways such as pH homeostasis, molybdenum cofactor biosynthesis, nitrate metabolism, and transport. In addition, nucleosides have various applications, such as antiviral drugs. Thus, the elucidation of the transport mechanism of nucleosides could be helpful for the construction of engineered strains for nucleoside production.
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Baral KC, Bajracharya R, Lee SH, Han HK. Advancements in the Pharmaceutical Applications of Probiotics: Dosage Forms and Formulation Technology. Int J Nanomedicine 2021; 16:7535-7556. [PMID: 34795482 PMCID: PMC8594788 DOI: 10.2147/ijn.s337427] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Probiotics have demonstrated their high potential to treat and/or prevent various diseases including neurodegenerative disorders, cancers, cardiovascular diseases, and inflammatory diseases. Probiotics are also effective against multidrug-resistant pathogens and help maintain a balanced gut microbiota ecosystem. Accordingly, the global market of probiotics is growing rapidly, and research efforts to develop probiotics into therapeutic adjuvants are gaining momentum. However, because probiotics are living microorganisms, many biological and biopharmaceutical barriers limit their clinical application. Probiotics may lose their activity in the harsh gastric conditions of the stomach or in the presence of bile salts. Moreover, they easily lose their viability under thermal or oxidative stress during their preparation and storage. Therefore, stable formulations of probiotics are required to overcome the various physicochemical, biopharmaceutical, and biological barriers and to maximize their therapeutic effectiveness and clinical applicability. This review provides an overview of the pharmaceutical applications of probiotics and covers recent formulation approaches to optimize the delivery of probiotics with particular emphasis on various dosage forms and formulation technologies.
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Affiliation(s)
- Kshitis Chandra Baral
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
| | - Rajiv Bajracharya
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
| | - Sang Hoon Lee
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
| | - Hyo-Kyung Han
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea
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Abdelkader H, Fathalla Z, Seyfoddin A, Farahani M, Thrimawithana T, Allahham A, Alani AWG, Al-Kinani AA, Alany RG. Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants. Adv Drug Deliv Rev 2021; 177:113957. [PMID: 34481032 DOI: 10.1016/j.addr.2021.113957] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/13/2021] [Accepted: 08/29/2021] [Indexed: 02/07/2023]
Abstract
Non-oral long-acting drug delivery systems (LADDS) encompass a range of technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized injections for treating chronic diseases like diabetes, cancer, and brain disorders as well as for age-related eye diseases. LADDS have been shown to prolong drug release from 24 h up to 3 years depending on characteristics of the drug and delivery system. LADDS can offer potentially safer, more effective, and patient friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. Whilst there is no single technology or definition that can comprehensively embrace LADDS; for the purposes of this review, these systems include solid implants, inserts, transdermal patches, wafers and in situ forming delivery systems. This review covers common chronic illnesses, where candidate drugs have been incorporated into LADDS, examples of marketed long-acting pharmaceuticals, as well as newly emerging technologies, used in the fabrication of LADDS.
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Affiliation(s)
- Hamdy Abdelkader
- Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, New Minia City, Minia, Egypt
| | - Zeinab Fathalla
- Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, Egypt
| | - Ali Seyfoddin
- Drug Delivery Research Group, Faculty of Health and Environmental Sciences, School of Science, Auckland University of Technology, New Zealand
| | - Mojtaba Farahani
- Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran
| | - Thilini Thrimawithana
- Discipline of Pharmacy, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia
| | - Ayman Allahham
- Discipline of Pharmacy, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia
| | - Adam W G Alani
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Moody Avenue, RLSB, Portland, OR, United States; Biomedical Engineering Department, Oregon Health & Science University, 2730 S. Moody Avenue, RLSB, Portland, OR, United States; Knight Cancer Institute, Oregon Health & Science University, 2730 S. Moody Avenue, RLSB, Portland, OR, United States
| | - Ali A Al-Kinani
- Drug Discovery, Delivery and Patient Care Theme (DDDPC), Faculty of Science, Engineering and Computing, Kingston University London, Penrhyn Road, Kingston upon Thames, UK.
| | - Raid G Alany
- Drug Discovery, Delivery and Patient Care Theme (DDDPC), Faculty of Science, Engineering and Computing, Kingston University London, Penrhyn Road, Kingston upon Thames, UK; School of Pharmacy, The University of Auckland, Auckland, New Zealand.
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Stabilization of Lipid Lamellar Bilayer Structure of Stratum Corneum Modulated by Poly (2-methacryloyloxyethyl phosphorylcholine) in Relation to Skin Hydration and Skin Protection. Tissue Eng Regen Med 2021; 18:953-962. [PMID: 34460064 DOI: 10.1007/s13770-021-00379-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/14/2021] [Accepted: 07/16/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND One crucial factor in skin tissue engineering is to understand the hydration and barrier property of skin. We investigated the skin hydration and stabilization strategy of inter-lamellar structure of stratum corneum (SC) using poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC). METHODS The unique hydration and stabilization potency of PMPC on the barrier function of the SC examined using freshly excised hairless mouse skin as a model membrane and the relationship between the stabilization of the lipid lamellar bilayer (LLB) and its enhanced water holding capacity was established. RESULTS Differential scanning calorimeter based on the phase-transition temperature of lipid domain of SC demonstrated that PMPC stabilized the LLB. The ratio of the heat of lipid phase transition (△H) of SC exposed to water and PMPC for 24 h was 1.51. X-ray crystallography showed the presence of well- organized lipids in intercellular membranes exhibiting short and long periodicity of lamellar phases. The peak at 4.4 nm attributed to the long periodicity phase (LPP) was missing in water-treated SC, where, the presence of 4.2- 4.4 nm peak in PMPC treated SC indicated that PMPC stabilized LPP. Transmission electron microscopy study demonstrated that the LLB structure became more rigid and orderly in PMPC treated SC. CONCLUSION The unique ion paired structure of PMPC enhances the barrier function of the SC by stabilizing LLB structure and hydration by inducing weakly bound water. The unique hydration state and stabilization effect from extended water exposure could provide a valuable information to prepare reliable artificial skin matrix and skin tissue.
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Yadav PR, Munni MN, Campbell L, Mostofa G, Dobson L, Shittu M, Pattanayek SK, Uddin MJ, Das DB. Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges. Pharmaceutics 2021; 13:1132. [PMID: 34452093 PMCID: PMC8401662 DOI: 10.3390/pharmaceutics13081132] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/17/2021] [Accepted: 07/20/2021] [Indexed: 12/14/2022] Open
Abstract
The ongoing search for biodegradable and biocompatible microneedles (MNs) that are strong enough to penetrate skin barriers, easy to prepare, and can be translated for clinical use continues. As such, this review paper is focused upon discussing the key points (e.g., choice polymeric MNs) for the translation of MNs from laboratory to clinical practice. The review reveals that polymers are most appropriately used for dissolvable and swellable MNs due to their wide range of tunable properties and that natural polymers are an ideal material choice as they structurally mimic native cellular environments. It has also been concluded that natural and synthetic polymer combinations are useful as polymers usually lack mechanical strength, stability, or other desired properties for the fabrication and insertion of MNs. This review evaluates fabrication methods and materials choice, disease and health conditions, clinical challenges, and the future of MNs in public healthcare services, focusing on literature from the last decade.
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Affiliation(s)
- Prateek Ranjan Yadav
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK; (P.R.Y.); (L.C.); (L.D.); (M.S.)
- Chemical Engineering Department, Indian Institute of Technology, Delhi 110016, India;
| | | | - Lauryn Campbell
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK; (P.R.Y.); (L.C.); (L.D.); (M.S.)
| | - Golam Mostofa
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (M.N.M.); (G.M.)
| | - Lewis Dobson
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK; (P.R.Y.); (L.C.); (L.D.); (M.S.)
| | - Morayo Shittu
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK; (P.R.Y.); (L.C.); (L.D.); (M.S.)
| | | | - Md. Jasim Uddin
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (M.N.M.); (G.M.)
- Department of Pharmacy, Brac University, 66 Mohakhali, Dhaka 1212, Bangladesh
| | - Diganta Bhusan Das
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK; (P.R.Y.); (L.C.); (L.D.); (M.S.)
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Moniz T, Costa Lima SA, Reis S. Marine polymeric microneedles for transdermal drug delivery. Carbohydr Polym 2021; 266:118098. [PMID: 34044917 DOI: 10.1016/j.carbpol.2021.118098] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 12/16/2022]
Abstract
Transdermal drug delivery is considered one of the most attractive routes for administration of pharmaceutic and cosmetic active ingredients due to the numerous advantages, especially over oral and intravenous methodologies. However, some limitations still exist mainly regarding the need to improve the drugs permeation across the skin. For this, several strategies have been described, considering the application of chemical permeation enhancers, drugs' nanoformulations and physical methods. Of these, microneedles have been proposed in the last years as promising strategies to enhance transdermal drug delivery. In this review, different types of microneedles are described, and the most commonly used methods of fabrication systematized, as well as the materials typically used and their main therapeutical applications. A special attention is paid to polymeric microneedles, particularly those made from sustainable marine polysaccharides like chitosan, alginate and hyaluronic acid. The applications of marine based polymeric microneedle devices for transdermal drug delivery are examined in detail and the perspectives of translation from the clinical trials to the market demonstrated.
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Affiliation(s)
- Tânia Moniz
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Sofia A Costa Lima
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
| | - Salette Reis
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
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Zeb A, Rana I, Choi HI, Lee CH, Baek SW, Lim CW, Khan N, Arif ST, Sahar NU, Alvi AM, Shah FA, Din FU, Bae ON, Park JS, Kim JK. Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals. Pharmaceutics 2020; 12:E1184. [PMID: 33291312 PMCID: PMC7762162 DOI: 10.3390/pharmaceutics12121184] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/02/2020] [Accepted: 12/02/2020] [Indexed: 12/13/2022] Open
Abstract
During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.
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Affiliation(s)
- Alam Zeb
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Isra Rana
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Ho-Ik Choi
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Cheol-Ho Lee
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Seong-Woong Baek
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Chang-Wan Lim
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Namrah Khan
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Sadia Tabassam Arif
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Najam us Sahar
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Arooj Mohsin Alvi
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Fawad Ali Shah
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Fakhar ud Din
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan;
| | - Ok-Nam Bae
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Jeong-Sook Park
- Institute of Drug Research and Development, College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
| | - Jin-Ki Kim
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
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13
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Keum T, Noh G, Seo JE, Bashyal S, Lee S. In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues. Pharmaceuticals (Basel) 2020; 13:ph13110408. [PMID: 33233392 PMCID: PMC7700664 DOI: 10.3390/ph13110408] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/10/2020] [Accepted: 11/19/2020] [Indexed: 12/25/2022] Open
Abstract
Buccal tissues are considered one of the potential alternative delivery route because of fast drug absorption and onset of action due to high vascularization and a non-keratinized epithelial membrane. In this study, the effect of Penetratin on the permeation of salmon calcitonin (sCT), a model macromolecular peptide drug, through TR146 buccal cells and porcine buccal tissues has been evaluated. To observe permeation profile of sCT, TR146 buccal cells were treated with Alexa 647 conjugated sCT (Alexa 647-sCT) with different concentrations of fluorescein isothiocyanate -labeled Penetratin (FITC-Penetratin) ranging from 0 to 40 μM, and analyzed using flow cytometry and confocal laser scanning microscopy. Intracellular penetration of FITC-Penetratin rapidly increased at low concentrations from 0 to 15 μM and it gradually increased at concentrations above 15 μM. Intracellular penetration of Alexa 647-sCT enhanced with the increase of FITC-Penetratin concentration. When TR146 cell layers and buccal tissues were co-treated with sCT and Penetratin as permeation enhancer, the flux of sCT increased as per Penetratin concentration. Compared to the control, 12.2 μM of Penetratin enhanced the flux of sCT in TR146 cell layers and buccal tissues by 5.5-fold and 93.7-fold, respectively. These results strongly suggest that Penetratin may successfully act as a non-invasive permeation enhancer for macromolecular peptide drug delivery through buccal routes.
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Affiliation(s)
- Taekwang Keum
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea; (T.K.); (G.N.); (J.-E.S.); (S.B.)
- Center for Forensic Pharmaceutical Science, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea
| | - Gyubin Noh
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea; (T.K.); (G.N.); (J.-E.S.); (S.B.)
- Center for Forensic Pharmaceutical Science, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea
| | - Jo-Eun Seo
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea; (T.K.); (G.N.); (J.-E.S.); (S.B.)
| | - Santosh Bashyal
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea; (T.K.); (G.N.); (J.-E.S.); (S.B.)
- Center for Forensic Pharmaceutical Science, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea
| | - Sangkil Lee
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea; (T.K.); (G.N.); (J.-E.S.); (S.B.)
- Center for Forensic Pharmaceutical Science, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea
- Correspondence: ; Tel.: +82-53-580-6655
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14
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Na YG, Kim M, Han M, Huh HW, Kim JS, Kim JC, Park JH, Lee HK, Cho CW. Characterization of Hepatitis B Surface Antigen Loaded Polylactic Acid-Based Microneedle and Its Dermal Safety Profile. Pharmaceutics 2020; 12:pharmaceutics12060531. [PMID: 32527003 PMCID: PMC7355901 DOI: 10.3390/pharmaceutics12060531] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 06/02/2020] [Accepted: 06/05/2020] [Indexed: 12/19/2022] Open
Abstract
A surge of interest in microneedle (MN) vaccines as a novel vaccination system has emerged. Before the clinical application of MN vaccine, an assessment of potential biological risks to skin and quality control of MN must be performed. Therefore, the present study aims to evaluate the physicochemical properties of MN and to evaluate the histological changes and inflammatory cell infiltrations after the application of MN with hepatitis B surface antigen (HBsAg). During in vitro and in vivo release testing, HBsAg MN released over 70% of HBsAg at 30 min. During the pyrogen test of HBsAg MN in rabbit, no rabbit showed an individual rise in temperature of 0.5 °C or more. MN with HBsAg produced the moderate immunization in mice. MN application did not alter the thickness of dermal and epidermal layers in mice. In addition, the topical applications of MN and MN for hepatitis B vaccine did not acutely induce the inflammation, allergic reaction, dermal toxicity and skin irritation. Thus, the MN system for the delivery of HBsAg could be the promising technology in the hepatitis B vaccination.
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Affiliation(s)
- Young-Guk Na
- College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (Y.-G.N.); (M.K.); (M.H.); (H.W.H.)
| | - Minki Kim
- College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (Y.-G.N.); (M.K.); (M.H.); (H.W.H.)
| | - Mingu Han
- College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (Y.-G.N.); (M.K.); (M.H.); (H.W.H.)
| | - Hyun Wook Huh
- College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (Y.-G.N.); (M.K.); (M.H.); (H.W.H.)
| | - Ji-Seok Kim
- Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University, Seongnam 13120, Korea; (J.-S.K.); (J.C.K.); (J.-H.P.)
| | - Jong Chan Kim
- Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University, Seongnam 13120, Korea; (J.-S.K.); (J.C.K.); (J.-H.P.)
| | - Jung-Hwan Park
- Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University, Seongnam 13120, Korea; (J.-S.K.); (J.C.K.); (J.-H.P.)
| | - Hong-Ki Lee
- College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (Y.-G.N.); (M.K.); (M.H.); (H.W.H.)
- Correspondence: (H.-K.L.); (C.-W.C.); Tel.: +82-42-821-7301 (H.-K.L.); +82-42-821-5934 (C.-W.C.); Fax: +82-42-823-6566 (H.-K.L.); +82-42-823-6566 (C.-W.C.)
| | - Cheong-Weon Cho
- College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (Y.-G.N.); (M.K.); (M.H.); (H.W.H.)
- Correspondence: (H.-K.L.); (C.-W.C.); Tel.: +82-42-821-7301 (H.-K.L.); +82-42-821-5934 (C.-W.C.); Fax: +82-42-823-6566 (H.-K.L.); +82-42-823-6566 (C.-W.C.)
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15
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Bashyal S, Shin CY, Hyun SM, Jang SW, Lee S. Preparation, Characterization, and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl. Pharmaceutics 2020; 12:pharmaceutics12030270. [PMID: 32188083 PMCID: PMC7151237 DOI: 10.3390/pharmaceutics12030270] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/11/2020] [Accepted: 03/12/2020] [Indexed: 12/31/2022] Open
Abstract
Transdermal delivery systems are emerging platforms for the delivery of donepezil hydrochloride (DH) for treating Alzheimer's disease. The primary aim of this study was to develop polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogels and to evaluate their feasibility for delivering DH via a transdermal route. Physicochemical properties, such as gel fraction (%), swelling ratio (%), weight loss (%), mechanical strength, elongation at break, and Young's modulus of the prepared hydrogels were evaluated. Furthermore, in vitro skin permeation and in vivo pharmacokinetic studies were performed. With an increased concentration of propylene glycol (PG), the gel fraction (%), maximum strength, and elongation at break decreased. However, the swelling ratio (%) and weight loss (%) of hydrogels increased with increased PG content. The 26% PG-hydrogel was superior, with an enhancement ratio of 12.9 (*** p < 0.001). In addition, the 11% PG-hydrogel and 1% PG-hydrogel exhibited an enhancement ratio 6.30-fold (*** p < 0.001) and 2.85-fold (* p < 0.05) higher than that exhibited by control, respectively, indicating a promising effect of PG on skin permeation. In addition, in vivo pharmacokinetic studies on hairless rats assessed the expediency for transdermal delivery of DH. The transdermal delivery of optimized hydrogel-patches with two different doses of DH revealed that the maximum plasma concentration and area under the curve were dose dependent, and the time to reach the maximum concentration was 8 h. Thus, optimized hydrogels have the potential to enhance the transdermal delivery of DH and could be a novel clinical approach.
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Affiliation(s)
- Santosh Bashyal
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea;
| | - Chang Yell Shin
- Research Institute of Dong-A ST Co. Ltd., Yongin 17073, Korea; (C.Y.S.); (S.M.H.)
| | - Sang Min Hyun
- Research Institute of Dong-A ST Co. Ltd., Yongin 17073, Korea; (C.Y.S.); (S.M.H.)
| | - Sun Woo Jang
- Research Institute of Dong-A ST Co. Ltd., Yongin 17073, Korea; (C.Y.S.); (S.M.H.)
- Correspondence: (S.W.J.); (S.L.); Tel.: +82-31-280-1324 (S.W.J.); +82-53-580-6655 (S.L.); Fax: +82-31-282-8564 (S.W.J.); +82-53-580-5164 (S.L.)
| | - Sangkil Lee
- College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea;
- Correspondence: (S.W.J.); (S.L.); Tel.: +82-31-280-1324 (S.W.J.); +82-53-580-6655 (S.L.); Fax: +82-31-282-8564 (S.W.J.); +82-53-580-5164 (S.L.)
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