Search Results (169)

Sea cucumber mouthpart peptides (SCPs) are marine bioactive peptides with considerable application potential. However, their oral delivery remains challenging because of their poor stability and low intestinal bioavailability. To develop a delivery system for SCPs with gastric protection and pH-responsive intestinal sustained-release properties, double-layer gel beads (SCP-BMs) were fabricated through ionic gelation, with SCPs as the core material and sodium alginate (SA) and chitosan (CS) as the wall materials. The preparation conditions of the gel beads were optimized using single-factor experiments and response surface methodology (RSM). The optimized gel beads were then characterized for their morphology, thermal stability, in vitro gastrointestinal release behavior, and antioxidant activity. The results showed that the optimal preparation conditions were 1.67% (w/v) sodium alginate, 0.96% (w/v) chitosan, and 2.16% (w/v) CaCl₂. Under the optimized conditions, the encapsulation efficiency (EE) reached 94.33%, significantly higher than that of the single-layer gel beads (SCP-SMs, 58.61%). Structural characterization showed that SCP-BMs exhibited a more compact structure than SCP-SMs, along with improved thermal stability. In vitro release and antioxidant assays demonstrated that SCP-BMs exhibited better gastric protection, pH-responsive intestinal release, and higher 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity compared with SCP-SMs. This study demonstrated that the SA/CS double-layer wall material system effectively improved the encapsulation efficiency, structural stability, and intestinal release behavior of SCP gel beads. These findings provide a feasible strategy for the development of SCP delivery systems and offer a theoretical basis for the high-value utilization of sea cucumber byproducts. Full article

Background/Objectives: Microcapsules are particles 1–1000 µm in size, with a core containing the active substance (in liquid, solid, or gaseous state) and a shell typically composed of natural, synthetic, or semi-synthetic polymers. Although natural polymer-based microcapsules have applications in food, cosmetics, and other industries, this review primarily focuses on their role in pharmaceutical drug delivery. In recent years, natural macromolecules have gained increasing attention as coating materials due to their biocompatibility, biodegradability, low toxicity, mucoadhesive properties, and ability to enable controlled and targeted drug release. Based on previous research, this review provides an overview of microcapsules, the most common microencapsulation methods, natural polymers used as wall materials, and their pharmaceutical applications across different routes of administration. Results: By encapsulating active ingredients, microcapsules enhance their bioavailability, prolong their release, protect them, enable targeted delivery, and mask unpleasant tastes and odors. Among the most commonly used microencapsulation techniques are physical methods (spray drying, spray cooling, solvent evaporation, spray coating, and freeze drying) and physicochemical methods (coacervation). Natural polymers, particularly polysaccharides and proteins, have been successfully used in oral, topical, transdermal, pulmonary, and colon-targeted drug delivery systems, as well as for the stabilization and delivery of peptides, proteins, probiotics, and vaccines. Conclusions: Proper selection of microencapsulation technique depends on the properties of the polymer and the core material. Natural polymers represent versatile pharmaceutical excipients owing to their biocompatibility, biodegradability, safety, mucoadhesive behavior, and ability to provide controlled and targeted drug delivery. Their successful application with a wide range of therapeutic agents and administration routes highlights their considerable potential for the development of advanced drug delivery systems. Full article

Background/Objectives: Tirzepatide is a dual GIP and GLP-1 receptor agonist indicated for the treatment of type 2 diabetes and obesity. Oral delivery of tirzepatide is limited by poor gastrointestinal permeability, pH-dependent solubility, and manufacturing challenges associated with high-dose absorption enhancers. Methods: This study developed an immediate-release oral tirzepatide tablet using a Quality by Design (QbD) approach. Sodium caprate (C10) was selected as the absorption enhancer based on acid-neutralizing capacity, Caco-2 permeability enhancement, and preliminary rat pharmacokinetic screening. Quality target product profile, critical quality attributes, preliminary hazard analysis, and failure mode and effects analysis identified binder/disintegrant ratios as critical material attributes and hammer milling conditions as critical process parameters. Face-centered central composite designs and multiple-response optimization (MRO) were applied to optimize dissolution, flowability, and tablet mechanical integrity. Results: The optimized binder/disintegrant composition produced benchmark-comparable dissolution profiles against oral semaglutide tablets in pH 1.2, 4.0, and 6.8 media, with f₂ values exceeding 50 for both C10 300 mg and 500 mg formulations. The optimized process yielded tablets with low friability (0.58%) and acceptable flowability (Carr’s index, 24). In beagle dogs, the C10 300 mg formulation achieved higher systemic exposure than the C10 500 mg formulation, with a C_max of 46.49 ± 23.79 ng/mL and AUC_last of 1261.03 ± 690.44 h·ng/mL. Conclusions: These results support C10-mediated oral tirzepatide delivery and QbD-based optimization for oral peptide tablets. Full article

Background/Objectives: Cyclotides are plant-derived macrocyclic peptides distinguished by their head-to-tail cyclized backbone and cystine knot motif, which confer remarkable stability against thermal, enzymatic, and chemical degradation. These features, combined with a compact and rigid structure, position cyclotides as promising scaffolds for future antibacterial agents in response to the escalating threat of multidrug-resistant (MDR) pathogens and the stagnation of conventional antibiotic discovery pipelines. This review summarizes the structural features, antibacterial mechanisms, bioengineering strategies, and translational potential of cyclotides against MDR infections. Methods: A narrative review of the literature was conducted using recent original research articles and reviews on cyclotide structure, antibacterial activity, bioengineering, computational modeling, and pharmaceutical applications. Results: Cyclotides exhibit potent antimicrobial activity, primarily through membrane disruption mediated by amphipathic surfaces and affinity for anionic bacterial membranes. Some variants also demonstrate anti-virulence and antibiofilm properties, broadening their therapeutic relevance for difficult-to-treat infections. Bioengineering approaches, including epitope grafting and rational design, have improved selectivity and potency while reducing cytotoxicity. Advances in computational modeling, molecular dynamics, and artificial intelligence have accelerated the prediction and optimization of antimicrobial activity, toxicity, and pharmacokinetic properties. Conclusions: Innovations in synthesis, including recombinant expression and enzymatic ligation, are helping overcome translational barriers related to cost and scalability. Although challenges remain in oral bioavailability and systemic delivery, strategies such as lipidation and scaffold modification support the development of cyclotide-based therapeutics as adaptable platforms for peptide drug discovery. Full article

Mucoadhesive drug delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of pharmaceuticals by improving drug residence time, bioavailability, and site-specific targeting. Among various materials investigated, biopolysaccharides have gained significant attention due to their biocompatibility, biodegradability, non-toxicity, and inherent mucoadhesive properties. Natural polymers such as chitosan, alginate, pectin, hyaluronic acid, and cellulose derivatives exhibit strong interactions with mucosal surfaces through hydrogen bonding, electrostatic interactions, and polymer chain entanglement. These properties enable prolonged drug retention at mucosal sites, controlled drug release, and enhanced permeation across biological barriers. Mucoadhesive biopolysaccharides have been explored for diverse routes of administration, including oral, buccal, nasal, ocular, vaginal, and pulmonary delivery. Furthermore, chemical modification and nanostructuring of these polymers have expanded their functionality, enabling targeted delivery of small molecules, proteins, peptides, and nucleic acids. This review highlights the mechanisms of mucoadhesion, key biopolysaccharides used in drug delivery, formulation approaches, and recent advances in their application as versatile platforms for novel therapeutic delivery systems. The continued development of mucoadhesive biopolysaccharide-based carriers holds substantial potential for improving treatment outcomes and patient compliance. Full article

Food-derived bioactive peptides have become a research hotspot in diabetes nutritional intervention due to their high safety, wide availability, and multi-target activities. This review addresses this by proposing a systems biology integration framework that defines these peptides as pleiotropic regulators of the gut microbiota-immune inflammation-metabolic signaling network, offering a novel systems-level perspective beyond previous reviews focused on single enzymes or pathways. The framework consists of three synergistic tiers. Tier 1 inhibits α-amylase, α-glucosidase or dipeptidyl peptidase-IV (DPP-IV) to control postprandial blood glucose. Tier 2 corrects insulin resistance by modulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), activating nuclear factor erythroid 2-related factor 2 (Nrf2), and suppressing nuclear factor kappa-B (NF-κB). Tier 3 uses the gut as a hub to remotely coordinate metabolism via the gut–liver and gut–pancreas axes. The review also systematically summarizes the major sources and preparation methods of food-derived antidiabetic peptides, analyzes their advantages including multi-target network regulation, safety, and sustainability, as well as challenges such as oral bioavailability, insufficient clinical evidence, processing stability, and regulatory hurdles. Finally, it outlines future directions focusing on three actionable priorities: AI-assisted design, oral delivery systems, and high-quality clinical studies. This framework offers a new perspective for applying food-derived peptides in precision nutrition intervention for diabetes. Full article

Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety. Full article

To address the poor solubility, instability, and low oral bioavailability of quercetin (Q), Q-loaded nanoparticles (Q@DDZ) were fabricated using deamidated zein peptide (DDZ) via a pH-driven method. As a food-grade hydrophilic colloid, DDZ effectively improves the colloidal stability of the delivery system. Deamidation increased hydrophilic amino acids and surface negative charge. DDZ bound Q via static quenching with a higher binding constant (K_a = 2.25 × 10³ L/mol) and more binding sites (n = 1.7561) than zein, along with stronger hydrogen bonding and hydrophobic interactions. Q@DDZ exhibited higher encapsulation efficiency (45.36–87.32%) and loading capacity (1.82–12.27%) than Q@zein, with a smaller particle size and better dispersibility. At 50.0 μg/mL Q, Q@DDZ showed 41.06% (DPPH) and 46.62% (ABTS) higher scavenging rates than free Q. It displayed excellent stability under acidic, high ionic strength, and thermal conditions (80 °C, 180 min). In simulated digestion, Q@DDZ delayed Q release in the oral and gastric phases and prolonged intestinal release, which indicated potentially improved bioavailability. This study provides mechanistic insights into deamidation-modified plant protein delivery systems for hydrophobic bioactives, offering new perspectives for the development of functional biopolymer gel materials. Full article

Background/Objectives: Oral delivery of semaglutide (Rybelsus) relies on sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC) to enhance peptide absorption. However, formulation constraints and SNAC’s localized gastric mechanism have prompted the exploration of alternative enhancers. This study evaluated whether sodium caprate (C10), a well-characterized medium-chain fatty acid (MCFA), could achieve systemic exposure comparable to SNAC-based formulations when co-formulated in an immediate-release (IR) tablet. Methods: Preformulation studies assessed the physicochemical properties and buffering capacity of C10. Mechanistic feasibility was evaluated through Caco-2 transport studies and rat pharmacokinetic (PK) trials using aqueous suspensions, comparing the concentration-dependent effects of C10 and SNAC. Based on these findings, three IR tablet architectures (monolayer, bilayer, and dry compression-coated) were developed. The optimized formulation was evaluated in beagle dogs (14 mg semaglutide) and compared with the SNAC-based reference product. Results: C10 exhibited sufficient buffering capacity to neutralize acidic environments. In Caco-2 and rat PK studies, C10 enhanced semaglutide absorption in a concentration-dependent manner, yielding exposure levels equivalent to SNAC at matched doses. Among the tablet designs, the monolayer tablet showed the highest dissolution similarity (f₂ = 67.8) to Rybelsus. In beagle dogs, the optimized monolayer formulation produced pharmacokinetic parameters, including C_max, AUC_last, and t_1/2, that overlapped with those of the SNAC-based reference drug product under matched dosing conditions. Conclusions: These results demonstrate that C10 can effectively support oral semaglutide delivery when incorporated into a rationally designed IR tablet. The findings support the feasibility of MCFA-based permeation enhancer platforms as formulation alternatives to SNAC for oral peptide therapeutics. Full article

Background/Objectives: BPC-157 (body protection compound 157) is a synthetic pentadecapeptide derived from a gastric protein fragment with reported cytoprotective and regenerative properties across multiple organ systems. Despite over three decades of preclinical research demonstrating consistent biological activity, its pharmaceutical development remains rudimentary, with no approved formulation, no validated dosing regimen, and no completed Phase II clinical trial. This review critically evaluates BPC-157 from a biopharmaceutical and drug development perspective, examining its physicochemical and pharmacokinetic properties, formulation challenges across routes of administration, the pharmacokinetic–pharmacodynamic disconnect that characterizes its preclinical profile, and the regulatory and translational barriers that currently preclude clinical advancement. Methods: A narrative review of the literature was conducted using PubMed/MEDLINE, Embase, and Cochrane Library from database inception to April 2026. Search terms included “BPC-157”, “BPC157”, “body protection compound 157”, “pentadecapeptide”, and “GEPPPGKPADDAGLV”, each combined with “pharmacokinetics”, “formulation”, “biopharmaceutics”, “drug delivery”, “clinical trial”, “toxicology”, and “regulatory”. Patent databases (Espacenet, Google Patents) and regulatory agency websites (FDA, EMA, WADA) were searched independently. Searches were supplemented by forward and backward citation tracking of key references. Articles were selected based on relevance to biopharmaceutical characterization, pharmacokinetics, formulation science, clinical evidence, and regulatory status; pharmacodynamic studies were included insofar as they inform translational development. Evidence was synthesized with emphasis on pharmaceutical characterization, formulation science, and translational feasibility; no formal quality assessment instrument was applied, consistent with the narrative review design. Results: BPC-157 exhibits unusual stability in gastric juice and demonstrates activity via oral, parenteral, and topical routes, yet its human pharmacokinetic profile remains critically undercharacterized despite a recently published formal preclinical ADME study in two species confirming a sub-30-min plasma half-life, linear dose-proportional kinetics, and intramuscular bioavailability of 14–51% depending on species. A plasma half-life of under 30 min—confirmed preclinically and in a preliminary two-subject human pilot—contrasts with prolonged biological effects lasting hours to days—a disconnect with significant implications for dosing strategy and formulation design. No pharmaceutical-grade formulation has been developed or validated. The peptide lacks bcs classification data, permeability characterization, and formal excipient compatibility studies. Available clinical data derive from fewer than 30 subjects across three uncontrolled pilot studies, none of which employed standardized pharmaceutical preparations. Conclusions: BPC-157 presents a compelling but pharmaceutically underdeveloped profile. The primary barrier to clinical translation is not the absence of biological activity, but the absence of fundamental pharmaceutical science: characterized formulations, validated pharmacokinetics, and a coherent drug development strategy. Addressing these biopharmaceutical gaps is a prerequisite for any meaningful clinical program. Full article

The obesity–metabolic syndrome–diabetes continuum is driven by interconnected mechanisms including insulin resistance, dysfunctional adiposity, chronic inflammation and progressive cardio–renal–metabolic injury. This triggered a need for therapies that extend beyond glucose lowering alone. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as disease-modifying drugs include weight loss, cardiovascular risk reduction, glycemic control and renal protection. However, treatment burden, adherence issues and access restrictions may limit the long-term effects of injectable formulations. One significant translational development that aims to close this gap is oral GLP-1-based treatments. In this review, we examine the mechanistic rationale, formulation science and clinical development of oral GLP-1 RAs. Oral semaglutide is presented as the first validated proof of concept for systemic peptide delivery by the gastrointestinal route. The biological barriers to oral peptide absorption, including enzymatic degradation, low epithelial permeability, pharmacokinetic variability and epithelial safety constraints, are critically discussed. Enabling technologies such as SNAC-based gastric absorption, nanocarriers, mucoadhesive systems and stability-optimization platforms are evaluated. Evidence from the PIONEER program and related studies demonstrating meaningful glycemic and weight-loss efficacy, acceptable safety and clinical utility in patients with type 2 diabetes and chronic kidney disease is further synthesized. Beyond first-generation oral peptide platforms, we discuss the emerging landscape of non-peptide oral GLP-1 RAs, dual and triple incretin agonists, precision dosing strategies and model-informed drug development. Oral GLP-1-based therapeutics are shifting from a formulation breakthrough to a broader translational strategy for disease modification across the obesity–metabolic syndrome–diabetes continuum. Long-term renal outcomes, access and implementation barriers remain important priorities for future research. Full article

Plant-derived peptides have become one of the most promising classes of compounds in cancer research due to their specificity, safety, and different therapeutic actions. Generally, plant peptides have a size of 2 to 100 amino acids, and they can be extracted from different parts of the plant including leaves, seeds, stems, and roots. The present review brings together more than 300 prominent plant peptides, their sources, structural classes, extraction methods, anticancer effects, and mechanisms of action. We show the cytotoxicity of plant peptides against a wide range of human cancer cell lines (such as MCF-7, A549, HL-60, and HCT-116), as well as their effectiveness in preclinical animal models of cancer, where they resulted in lesser tumor growth and metastasis. Moreover, we go into the anticancer activity of plant peptides and reveal the interconnectedness of apoptosis, cell cycle arrest, angiogenesis inhibition, metastasis suppression, and the modulation of signaling pathways as some of the mechanisms through which plant peptides perform. In addition to their therapeutic potential, many of these peptides are derived from edible plant sources and can be delivered through functional foods or dietary supplements, offering a promising avenue for cancer prevention and adjunctive nutritional support. The review also touches upon the major hurdles in peptide drug development at present, such as stability, oral bioavailability, and large-scale production, while at the same time giving future perspectives that include bioengineering, nanotechnology-based delivery systems, and combination therapies for translating these natural products into clinical oncotherapeutics and health-promoting foods Full article

Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, pharmacokinetic constraints, and disruption of the commensal microbiome, leading to inconsistent outcomes and disease recurrence. This review highlights the mechanistic limitations of conventional antibiotic therapies in periodontitis and critically examines emerging next-generation therapeutic strategies aimed at overcoming these challenges. Specifically, it explores antimicrobial peptides, quorum sensing inhibitors, nanotechnology-based drug delivery systems, host modulation approaches, and microbiome-targeted therapies, with emphasis on their molecular mechanisms, clinical relevance, and translational potential. By integrating microbial, host, and pharmacological perspectives, this review provides a comprehensive framework for advancing precision-guided periodontal therapy and supports the shift toward targeted, sustainable, and personalized treatment strategies. Full article

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated substantial efficacy in improving glycemic control and reducing body weight. However, subcutaneous injection is poorly adherent for patients. To improve treatment compliance, we developed a poly(lactic-co-glycolic acid) (PLGA)-based nanovesicle (PLGA-Lira-NV) system for the oral delivery of Lira using a double-emulsion solvent evaporation technique. The optimized formulation yielded a narrow size distribution and high encapsulation efficiency (>95%). In vitro release studies showed that PLGA-Lira-NVs remained relatively stable under acidic conditions (pH 1.2 to 6.8) and exhibited sustained drug release in a neutral environment (pH 7.4), enabling protection of the fragile peptide in the stomach and controlled release after crossing the intestine. Following oral administration to obese mice (10 mg/kg), PLGA-Lira-NVs achieved prolonged glycemic control for up to 72 h. Notably, body weight decreased to 83% of baseline after 12 days, outperforming the subcutaneous injection (free Lira) group (88%). The consistent trend toward weight reduction confirms the sustained-release properties of PLGA nanocarrier for Lira, highlighting its potential to reduce dosing frequency and improve patient compliance. Collectively, these findings underscore the promising potential of PLGA nanovesicles as an oral delivery platform for peptide therapeutics. Full article