Colorectal cancer (CRC) is the third most frequent cancer worldwide. Despite advances in treatment, conventional chemotherapy suffers from severe side effects and limited drug selectivity, highlighting the importance of alternative therapies. In this study, a polymer-lipid hybrid microcarrier was developed for oral co-administration of paclitaxel (PTX) and tributyrin (TB) as a novel approach for CRC therapy. The microcarrier was designed with a pH-sensitive polymeric shell that encapsulates drug-loaded nanostructured lipid carriers (NLC); shell dissolution at intestinal pH enables localized release of the NLC. The methodological approach employed an emulsion of vegetable oil and NLC as a template for polymer deposition. Multiple parameters were optimized, including polymers ratios, NLC dilution, acid concentration, and sonication time. Spherical hybrid particles with smooth surface and mean size of 1000 nm were obtained; PTX encapsulation efficiency was 99.9 ± 0.2 %, with a production yield of 97.2 ± 0.08 %. Drug release followed the Korsmeyer-Peppas kinetic model. Cytotoxic evaluation in human colorectal adenocarcinoma HCT-116 monolayers showed that PTX encapsulation increased cytotoxicity, lowering IC50 to 83.7 nM compared to 199.5 nM for free PTX. The addition of TB further improved cytotoxicity, reducing the IC50 to 60.8 nM. A similar potentiation cytotoxicity was observed in spheroids. The microcarrier induced reductions in colony formation, alterations in cell cytoskeleton, and led to a significant reduction in P-glycoprotein expression compared to its free form, suggesting its potential to help to overcome drug resistance. These results point to the promising applicability of the hybrid microcarrier as an innovative delivery system for oral administration of cytotoxic agents.

Ulcerative colitis (UC) is a chronic autoimmune disease and seriously affects the normal life of patients. Conventional therapeutic drugs are difficult to meet clinical needs. Traditional Chinese medicine (TCM) ingredients could effectively alleviate the symptoms of UC by anti-inflammatory, anti-oxidative, regulating the gut microbiota, and repairing the colonic epithelial barrier, but their low solubility and bioavailability severely limit their clinical application. Nano-drug delivery systems (NDDS) combined with TCM ingredients is a promising option for treating UC, and they could significantly enhance the stability, solubility, and bioavailability of TCM ingredients. The review describes the anti-UC mechanisms of TCM ingredients, systematically summarizes various kinds of NDDS for TCM ingredients according to different routes of administration, and highlights the advantages of NDDS for TCM ingredients in the treatmentof UC. In addition, we discuss the limitations of existing NDDS for TCM ingredients and the development direction in the future. This review will provide a basis for the future development of anti-UC NDDS for TCM ingredients.

Over the past decade, new technologies have emerged to increase intrinsic potency, enhance bioavailability, and improve targeted delivery of drugs. Most pharmaceutical formulations require multiple dosing due to their fast release and short elimination kinetics, increasing the risk of adverse events and patient non-compliance. Due to these limitations, enormous efforts have focused on developing drug delivery systems (DDSs) for sustained release and targeted delivery. Sustained release strategies began with pioneering research using silicone rubber embedding for small molecules and non-inflammatory polymer encapsulation for proteins or DNA. Subsequently, numerous DDSs have been developed as controlled-release formulations to deliver systemic or local therapeutics, such as small molecules, biologics, or live cells. In this review, we discuss the latest developments of DDSs, specifically nanoparticles, hydrogels, and microgrippers for the delivery of systemic or localized drugs to the gastrointestinal (GI) tract. We examine innovative DDS design and delivery strategies tailored to the GI tract's unique characteristics, such as its extensive length and anatomical complexity, varying pH levels and enzymatic activity across different sections, and intrinsic peristalsis. We particularly emphasize those designed for the treatment of inflammatory bowel disease (IBD) with in vivo preclinical studies.

The bioavailability of small-molecule drugs remains a critical challenge in pharmaceutical development, significantly impacting therapeutic efficacy and commercial viability. This review synthesizes recent advances in understanding and overcoming bioavailability limitations, focusing on key physicochemical and biological factors influencing drug absorption and distribution. We examine cutting-edge strategies for enhancing bioavailability, including innovative formulation approaches, rational structural modifications, and the application of artificial intelligence in drug design. The integration of nanotechnology, 3D printing, and stimuli-responsive delivery systems are highlighted as promising avenues for improving drug delivery. We discuss the importance of a holistic, multidisciplinary approach to bioavailability optimization, emphasizing early-stage consideration of ADME properties and the need for patient-centric design. This review also explores emerging technologies such as CRISPR-Cas9-mediated personalization and microbiome modulation for tailored bioavailability enhancement. Finally, we outline future research directions, including advanced predictive modeling, overcoming biological barriers, and addressing the challenges of emerging therapeutic modalities. By elucidating the complex interplay of factors affecting bioavailability, this review aims to guide future efforts in developing more effective and accessible small-molecule therapeutics.

Intestinal dysfunction is becoming increasingly associated with neurological and endocrine issues, raising concerns about its impact on world health. With the introduction of several breakthrough technologies for detecting and treating intestinal illnesses, significant progress has been made in the previous few years. On the other hand, traditional intrusive diagnostic techniques are expensive and time-consuming. Furthermore, the efficacy of conventional drugs (not capsules) is reduced since they are more likely to degrade before reaching their target. In this context, microcapsules based on different types of biological macromolecules have been used to encapsulate active drugs and sensors to track intestinal ailments and address these issues. Several biomacromolecules/biomaterials (natural protein, alginate, chitosan, cellulose and RNA etc.) are widely used for make microcapsules for intestinal diseases, and can significantly improve the therapeutic effect and reduce adverse reactions. This article systematically summarizes microencapsulated based on biomacromolecules material for intestinal health control and efficacy enhancement. It also discusses the application and mechanism research of microencapsulated biomacromolecules drugs in reducing intestinal inflammation, in addition to covering the preparation techniques of microencapsulated drug delivery systems used for intestinal health. Microcapsule delivery systems' limits and potential applications for intestinal disease diagnosis, treatment, and surveillance were highlighted.

Inflammatory bowel disease (IBD) represents a significant global health challenge, and there is an urgent need to explore novel therapeutic interventions. Natural products have demonstrated highly promising effectiveness in the treatment of IBD.

This study systematically reviews the latest research advancements in leveraging natural products for IBD treatment.

This manuscript strictly adheres to the PRISMA guidelines. Relevant literature on the effects of natural products on IBD was retrieved from the PubMed, Web of Science and Cochrane Library databases using the search terms "natural product," "inflammatory bowel disease," "colitis," "metagenomics", "target identification", "drug delivery systems", "polyphenols," "alkaloids," "terpenoids," and so on. The retrieved data were then systematically summarized and reviewed.

This review assessed the different effects of various natural products, such as polyphenols, alkaloids, terpenoids, quinones, and others, in the treatment of IBD. While these natural products offer promising avenues for IBD management, they also face challenges in terms of clinical translation and drug discovery. The advent of metagenomics, single-cell sequencing, target identification techniques, drug delivery systems, and other cutting-edge technologies heralds a new era in overcoming these challenges.

This paper provides an overview of current research progress in utilizing natural products for the treatment of IBD, exploring how contemporary technological innovations can aid in discovering and harnessing bioactive natural products for the treatment of IBD.

Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.

The intestine is essential for the modulation of nutrient absorption and the removal of waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and celiac disease, which extensively impact gut functions, are thus critical for human health. Targeted drug delivery is essential to tackle these diseases, improve therapy efficacy, and minimize side effects. Recent strategies have taken advantage of both active and passive nanocarriers, which are designed to protect the drug until it reaches the correct delivery site and to modulate drug release via the use of different physical-chemical strategies. In this systematic review, we present a literature overview of the different nanocarriers used for drug delivery in a set of chronic intestinal pathologies, highlighting the rationale behind the controlled release of intestinal therapies. The overall aim is to provide the reader with useful information on the current approaches for gut targeting in novel therapeutic strategies.

Over the past decade, researchers have proposed a new class of drug delivery systems, bio-hybrid micro-robots, designed with a variety of living cell-driven micro-robots that utilize the unique mobility of natural organisms (bacteria, cells, exosomes, etc.) to transport effective drugs. Microalgae are considered potential drug delivery carriers. Recent studies have shown that microalga-based drug delivery systems exhibit excellent biocompatibility. In addition, microalgae have a large surfactant area, phototaxis, oxygen production, and other characteristics, so they are used as a carrier for the treatment of bacterial infections, cancer, etc. This review summarizes the modification of microalgae including click chemistry and electrostatic adsorption, and can improve the drug loading efficiency through dehydration and hydration strategies. The prepared microalgal drug delivery system can be targeted to different organs by different dosing methods or using external forces. Finally, it summarizes its antibacterial (gastritis, periodontitis, skin wound inflammation, etc.) and antitumor applications.

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that affects the entire gastrointestinal tract and is associated with an increased risk of colorectal cancer. Mainstream clinical testing methods are time-consuming, painful for patients, and insufficiently sensitive to detect early symptoms. Currently, there is no definitive cure for IBD, and frequent doses of medications with potentially severe side effects may affect patient response. In recent years, nanomaterials have demonstrated considerable potential for IBD management due to their diverse structures, composition, and physical and chemical properties. In this review, we provide an overview of the advances in nanomaterial-based diagnosis and treatment of IBD in recent five years. Multi-functional bio-nano platforms, including contrast agents, near-infrared (NIR) fluorescent probes, and bioactive substance detection agents have been developed for IBD diagnosis. Based on a series of pathogenic characteristics of IBD, the therapeutic strategies of antioxidant, anti-inflammatory, and intestinal microbiome regulation of IBD based on nanomaterials are systematically introduced. Finally, the future challenges and prospects in this field are presented to facilitate the development of diagnosis and treatment of IBD.

Gegen Qinlian Decoction, derived from Zhang Zhongjing's Treatise on Typhoid Fever, has been widely used in the treatment of various common diseases, frequently-occurring diseases and difficult and complicated diseases, such as ulcerative colitis. In this study, Bletilla striata polysaccharide (BSP) was innovatively used as a film coating material to prepare Gegen Qinlian pellets with dual sensitivity of pH enzyme for the treatment of ulcerative colitis. BSP has the ability to repair the inflamed colon mucosa and can produce synergistic effects, while avoiding the adverse therapeutic effects caused by the early release of drugs from a single pH-sensitive pellets in the small intestine. The prepared pellets have a uniform particle size, good roundness, a particle size range from 0.8 mm to 1.0 mm, and a particle yield is 85.6 %. The results of in vitro release showed that ES-BSP pellets hardly released drugs in the pH range of 1.2-6.8. However, in the colon mimic fluid containing specific enzymes, the drug release was significantly accelerated, demonstrating the sensitivity of the pellets to pH enzymes. In vivo and ex vivo fluorescence imaging of small animals showed that Gegen Qinlian pellets with dual sensitivity of pH enzyme remained longer in the colon compared with pH-sensitive pellets. In vivo pharmacodynamics study showed that the Gegen Qinlian pellets with dual sensitivity of pH enzyme had a better therapeutic effect in the rat model of the ulcerative colon than the commercially available Gegenqinlian pellets in the control group.

The purpose of this study was to evaluate the drug delivery and therapeutic potential of berberine (Br) loaded nanoformulation in rheumatoid arthritis (RA)-induced animal model.

The Br-loaded NLCs (nanostructured lipid carriers) were prepared employing melt-emulsification process, and optimized through box-behnken design. The prepared NLCs were assessed for in-vitro and in-vivo evaluations.

The optimized NLCs exhibited a mean diameter of 180.2 ± 0.31nm with 88.32 ± 2.43% entrapment efficiency. An enhanced anti-arthritic activity with reduced arthritic scores to 0.66 ± 0.51, reduction in ankle diameter to 5.80 ± 0.27mm, decline in paw withdrawal timing, and improvements in walking behavior were observed in the Br-NLCs treated group. The radiographic images revealed a reduction in bone and cartilage deformation.

The Br-NLCs showed promising results in the management of RA disease, can be developed as an efficient delivery system at commercial levels, and may be explored for clinical application after suitable experiments in the future.

Barberry (Berberis vulgaris L.) is a medicinal plant and its main constituent is an isoquinoline alkaloid named berberine that has multiple pharmacological effects such as antioxidant, anti-microbial, antiinflammatory, anticancer, anti-diabetes, anti-dyslipidemia, and anti-obesity. However, it has restricted clinical uses due to its very poor solubility and bioavailability (less than 1%). It undergoes demethylenation, reduction, and cleavage of the dioxymethylene group in the first phase of metabolism. Its phase two reactions include glucuronidation, sulfation, and methylation. The liver is the main site for berberine distribution. Berberine could excrete in feces, urine, and bile. Fecal excretion of berberine (11-23%) is higher than urinary and biliary excretion routes. However, a major berberine metabolite is excreted in urine greater than in feces. Concomitant administration of berberine with other drugs such as metformin, cyclosporine A, digoxin, etc. may result in important interactions. Thus, in this review, we gathered and dissected any related animal and human research articles regarding the pharmacokinetic parameters of berberine including bioavailability, metabolism, distribution, excretion, and drug-drug interactions. Also, we discussed and gathered various animal and human studies regarding the developed products of berberine with better bioavailability and consequently, better therapeutic effects.

Inflammatory bowel disease (IBD) is a chronic illness characterized by relapsing inflammation of the intestines. The disorder is stratified according to the severity and is marked by its two main phenotypical representations: Ulcerative colitis and Crohn's disease. Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition, environmental factors such as bacterial agents, and dysregulated immune response. Treatment for IBD aims to reduce symptom extent and severity and halt disease progression. The mainstay drugs have been 5-aminosalicylates (5-ASAs), corticosteroids, and immunosuppressive agents. Parenteral, oral and rectal routes are the conventional methods of drug delivery, and among all, oral administration is most widely adopted. However, problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery. Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues. Enteric-coated microneedle pills, various nano-drug delivery techniques, prodrug systems, lipid-based vesicular systems, hybrid drug delivery systems, and biologic drug delivery systems constitute some of these novel methods. Microneedles are painless, they dislodge their content at the affected site, and their release can be prolonged. Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells, including GM immune cells and red blood cells as nanoparticle carriers, can be plausible delivery methods when evaluating biologic systems. Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site. Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage. Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems, while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too. Leukosomes are also considered as possible carrier systems, and results from mouse models have revealed that they control anti- and pro-inflammatory molecules.

The incidence of inflammatory bowel disease (IBD) is rapidly rising throughout the world. Although tremendous efforts have been made, limited therapeutics are available for IBD management. Natural active small molecules (NASMs), which are a gift of nature to humanity, have been widely used in the prevention and alleviation of IBD; they have numerous advantageous features, including excellent biocompatibility, pharmacological activity, and mass production potential. Oral route is the most common and acceptable approach for drug administration, but the clinical application of NASMs in IBD treatment via oral route has been seriously restricted by their inherent limitations such as high hydrophobicity, instability, and poor bioavailability. With the development of nanotechnology, polymeric nanoparticles (NPs) have provided a promising platform that can efficiently encapsulate versatile NASMs, overcome multiple drug delivery barriers, and orally deliver the loaded NASMs to targeted tissues or cells while enhancing their stability and bioavailability. Thus, NPs can enhance the preventive and therapeutic effects of NASMs against IBD. Herein, we summarize the recent knowledge about polymeric matrix-based carriers, targeting ligands for drug delivery, and NASMs. We also discuss the current challenges and future developmental directions.