Search Results (1,370)

Background/Objectives: Sublingual vaccination offers a non-invasive route for inducing both systemic and mucosal immunity, yet the formulation properties that govern its success remain poorly defined. This study investigated the relationships among key formulation parameters for sublingual vaccines, such as viscosity, mucoadhesion, and mucosal residence, to understand their impact on in vivo immune responses in the sublingual delivery context. Methods: Ovalbumin (OVA)-based vaccine formulations containing cholera toxin B (CTB) adjuvant and mucoadhesive excipients such as hydroxypropyl methylcellulose (HPMC) or methylglycol chitosan (MGC), were evaluated for: (1) their respective rheological properties—characterized by viscosity and mucoadhesion parameters, as well as (2) in situ mucosal retention (assessed using Cy7-labeled formulations tracked by IVIS in vivo imaging system) and (3) in vivo immunogenicity via systemic (IgG) and mucosal (IgA) responses measured by ELISA, following sublingual administration to mice. Correlations between rheology, in situ/ex situ mucosal residence, and in vivo immune outcomes were determined. Results: Sublingual vaccine formulations containing HPMC exhibited the highest viscosity, mucoadhesion, and mucosal retention profiles, but paradoxically elicited the weakest systemic and mucosal antibody responses. In contrast, chitosan-based formulations enhanced immune responses even at reduced antigen and adjuvant doses, likely due to its permeation-enhancing and adjuvant effects. Correlation analyses revealed that while formulation viscosity and mucoadhesive strength were positively associated with mucosal retention, both rheological and retentive properties showed a significant inverse relationship with immunogenicity in the context of sublingual vaccine delivery. Conclusions: While viscosity and mucoadhesion are essential for in situ retention of sublingual vaccines, prolonged residence driven by excipient’s excessive rheological strength was found to reduce vaccine immunogenicity—likely due to restricted antigen release and mucosal uptake. Accordingly, HPMC appears suboptimal as a sublingual vaccine excipient, while chitosan shows promise for sublingual delivery as a permeation-enhancing adjuvant. These findings may shift the design paradigm for sublingual vaccine formulations, highlighting the need to balance mucosal retention with efficient antigen absorption for maximizing immune responses. Full article

Background: Although teriparatide is efficacious, its once-daily subcutaneous injections cause local adverse events, inconvenience, and higher cost, limiting long-term adherence. Therefore, this research aims to engineer a pH-responsive oral formulation of teriparatide for osteoporosis therapy. Methods: A layered silicate nanocomplex was obtained by spontaneous self-assembly of teriparatide (Teri) with 3-aminopropyl magnesium phyllosilicate (AC). The nanocomplex (AC-Teri) was then coated with a 1:1 blend of two polymethacrylic acid derivatives (Eudragit^® L100 and Eudragit^® S 100) to provide pH-triggered drug release along the gastrointestinal tract. Results: AC-Teri and the coated nanocomplex (EE/AC-Teri) displayed high encapsulation efficiency (>90%) with narrow size distributions. In a stepwise buffer transition system, EE/AC-Teri demonstrated pH-dependent release, with less than 25% drug liberated at pH 1.2, approximately 54% at pH 6.8, and 74% at pH 7.4 over 24 h. Particle size and ζ-potential of EE/AC-Teri shifted in parallel with dissolution of the outer polymer shell. EE/AC-Teri also protected the peptide against enzymatic degradation, preserving the secondary structure of encapsulated teriparatide in simulated intestinal fluids. Compared with free drug, EE/AC-Teri enhanced transcellular drug permeation 2.7-fold in Caco-2 cells. In dexamethasone-induced osteoporotic rats, oral EE/AC-Teri significantly stimulated bone formation while suppressing resorption; micro-CT and histology confirmed recovery of trabecular architecture. Conclusions: EE/AC-Teri represents a promising oral teriparatide formulation for the effective management of osteoporosis. Full article

Utilizing waste tire crumb rubber (CR) in asphalt modification is a promising method to enhance pavement performance while addressing the issue of waste tire disposal. Elevating CR content without compromising the pavement performance of asphalt is crucial for its practical and sustainable applications. However, conventional crumb-rubber-modified asphalt (CRMA) exhibits weakened physical and pavement properties when the CR content exceeds 25 wt%. Here, we propose a hybridization strategy combining CR and devulcanized CR (DCR) to produce high-performance modified asphalt with a total rubber content of up to 43wt%. Modified asphalt containing 30wt% CR and 13 wt% DCR (30CR-13DCRMA) demonstrates remarkable physical properties, with a softening point of 78.4 °C and a ductility of 15.33 cm. Rheology tests further reveal its superior rutting resistance (G*/sin δ), fatigue tolerance (G*·sin δ), and overall pavement performance compared to neat CR- or DCR-modified asphalt. Through rheological analysis, sol fraction measurement, gel permeation chromatography (GPC), and atomic force microscope (AFM) tests, it is revealed that the synergistic effect of CR and DCR can enhance the absorption capabilities of rubber particles, promoting their full swelling and resulting in a biphasic hard/soft microstructure within the asphalt matrix. This structural reorganization contributes to the outstanding comprehensive properties of this modified asphalt. This work establishes a hybrid-rubber asphalt system with high CR incorporation and well-balanced performance, offering a viable pathway toward sustainable pavement engineering. Full article

Large-format additive manufacturing (LFAM) is an enabling manufacturing technology capable of producing large parts with highly complex geometries for a wide variety of applications, including automotive, infrastructure/construction, and aerospace mold and tooling. In the past decade, the LFAM industry has seen widespread use of bio-based, glass, and/or carbon fiber reinforced thermoplastic composites which, when printed, serve as a lower-cost alternative to metallic parts. One of the highest-volume materials utilized by the industry is carbon fiber (CF)-filled polycarbonate (PC), which in out-of-autoclave applications can achieve comparable mechanical performance to metal at a significantly lower cost. Previous work has shown that if this material is recovered at various points throughout the manufacturing process for both the lab and pilot scale, it can be mechanically recycled with minimal impacts on the functional performance and printability of the material while significantly reducing the feedstock costs. End-of-life (EOL) CF-PC components were processed through industrial shredding, melt compounding, and LFAM equipment, followed by evaluation of the second-life material properties. Experimental assessments included quantitative analysis of fiber length attrition, polymer molecular weight degradation using gel permeation chromatography (GPC), density changes via pycnometry, thermal performance using dynamic mechanical analysis (DMA), and mechanical performance (tensile properties) in both the X- and Z-directions. Results demonstrated a 24.6% reduction in average fiber length compared to virgin prints, accompanied by a 21% decrease in X-direction tensile strength and a 39% reduction in tensile modulus. Despite these reductions, Z-direction tensile modulus improved by 4%, density increased by 6.8%, and heat deflection temperature (HDT) under high stress retained over 97% of its original value. These findings underscore the potential for integrating mechanically recycled CF-PC into industrial LFAM applications while highlighting the need for technological innovations to mitigate fiber degradation and enhance material performance for broader adoption. This critical step toward circular material practices in LFAM offers a pathway to reducing feedstock costs and environmental impact while maintaining functional performance in industrial applications. Full article

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide, with letrozole (LZ) serving as a critical aromatase inhibitor for hormone receptor–positive cases. However, long-term oral administration of LZ is often associated with systemic adverse effects and poor patient compliance. To overcome these limitations, new non-aqueous nanoemulgels (NEMGs) were developed for transdermal delivery of LZ. Methods: The NEMGs were formulated using glyceryl monooleate (GMO), Sepineo P600^®, Transcutol, propylene glycol, and penetration enhancers propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC), and Captex^®. Physicochemical characterization, solubility, stability, and in vitro permeation studies were conducted using Strat-M^® membranes, while in vivo pharmacokinetics were evaluated in rat models. Results: The optimized GMO/PGMC-based NEMG demonstrated significantly enhanced drug flux, higher permeability coefficients, and shorter lag times compared with other NEMGs and suspension emulgels. In vivo, transdermal application of the GMO/PGMC-based NEMG over an area of 2.55 cm² produced dual plasma absorption peaks, with 57% of the LZ dose absorbed relative to oral administration over 12 days. Shelf-life and accelerated stability assessments confirmed excellent physicochemical stability with negligible crystallization. Conclusions: The developed LZ NEMG formulations offer a stable, effective, and patient-friendly transdermal drug delivery platform for breast cancer therapy. This system demonstrates potential to improve patient compliance and reduce systemic toxicity compared to conventional oral administration. Full article

Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol^® P (diethylene glycol monoethyl ether), Capryol^® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol^® P and Capryol^® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10⁻⁵ cm²/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol^® P and Capryol^® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds. Full article

The cashew apple (Anacardium occidentale L.) is rich in antioxidant bioactive constituents that have anti-aging and wound healing properties. The objective of this study is to evaluate the biological activities of cashew apple extract (CAE) and to improve the issue involving the instability of ascorbic acid, the principal active compound, by encapsulating the extract in liposomes in order to enhance its stability and skin permeation for cosmetic applications. CAE was obtained from fresh cashew apple via ethanol maceration, solvent evaporation, and freeze-drying. Ascorbic acid content, total phenolic content (TPC), total flavonoid content (TFC), and total caffeoylquinic acid content (TCQAC) were determined. The ascorbic acid content and its tautomer in the extract were quantified using the LC-MS/MS method. Biological activities, including antioxidant, anti-tyrosinase, fibroblast collagen synthesis, cytoprotection against oxidative stress, wound healing, and cytotoxicity, were assessed. CAE was encapsulated in liposomes to enhance the stability of its inherent ascorbic acid and improve its skin in comparison to free-CAE. The CAE and liposomal-CAE were incorporated and formulated into a solution, and their physicochemical stability was assessed after storage. CAE appeared as a brown, viscous liquid with a characteristic sweet, fruity scent. Each gram of CAE contained 0.90 ± 0.05 mg of ascorbic acid, TPC, 81.40 ± 7.14 mg of gallic acid equivalents (GAE), TFC, 3.73 ± 0.30 mg of rutin equivalents (RE), and TCQAC, 4.48 ± 0.05 mg of chlorogenic acid equivalents (CGAE). CAE exhibited antioxidant properties (IC₅₀ = 282.19 ± 11.16 and 963.66 ± 3.95 µg/mL for DPPH and ABTS assay, respectively) and weak anti-tyrosinase activity (IC₅₀ = 4213.77 ± 138.97 µg/mL). It was non-cytotoxic to fibroblast and monocyte cells at a concentration of less than 1 mg/mL. In vitro wound healing assays demonstrated that CAE stimulated collagen production in a dose-dependent manner at CAE concentrations above 250 µg/mL. Additionally, CAE exhibited cytoprotective effects against H₂O₂-induced oxidative stress and did not induce inflammatory responses in immune cells. The liposomal formulation containing CAE achieved high encapsulation efficiency (79.75–84.55%) based on ascorbic acid content. In skin permeation studies, CAE-loaded liposomes demonstrated an enhancement ratio approximately two-fold greater than that of free-CAE. Stability testing over 3 months showed that the ascorbic acid content in CAE-loaded liposomes remained significantly higher than that in the free-CAE under both refrigerated and long-term conditions (30 °C/75% RH). CAE demonstrated potential anti-aging properties for improving aging skin. Liposomal incorporation markedly improved ascorbic acid stability and skin permeability. Full article

The use of lactose-utilizing microalgae offers a sustainable and cost-effective approach for the bioconversion of dairy industry side-streams and the reduction in microalgae production costs. This work aims to improve the biomass productivity of the lactose-utilizing microalgal strain Graesiella emersonii MSCL 1718 in concentrated cheese whey permeate. It was demonstrated that the mixotrophic growth of the axenic G. emersonii culture resulted in a significantly higher biomass productivity in 20% permeate medium compared to the heterotrophic cultivation. Furthermore, supplementation of the permeate medium with iron, zinc, cobalt, and molybdenum resulted in 12.8%, 12.9%, 9.3%, and 28.9% significant increases (p < 0.05) in biomass synthesis, respectively, compared to the control permeate group. In the subsequent experiment, G. emersonii cultivated in molybdenum-supplemented permeate resulted in 0.34 ± 0.02 g/(L·d) biomass productivity and twofold higher lipid content (30.21 ± 1.29%) compared to the photoautotrophic control in defined synthetic medium. Analysis of the fatty acid composition revealed a twofold increase in saturated fatty acids, reaching 62.16% under mixotrophic cultivation in permeate, compared with the photoautotrophic control. Overall, concentrated cheese permeate proved to be a suitable medium for G. emersonii biomass production, supporting both enhanced growth and increased lipid accumulation. Full article

Biomimetic lipid platforms provide versatile tools for mimicking various types of biological membranes and enable investigation of how industrially important amphiphiles (e.g., permeation enhancers and surfactants) interact with different membrane compositions. For example, antimicrobial lipids such as medium-chain fatty acids (FAs) and monoglycerides (MGs) are promising antibiotic alternatives that disrupt bacterial membranes and their distinct mechanisms of action are a topic of ongoing interest. The potency and targeting spectrum of individual antimicrobial lipids vary and mixing different lipids can improve functional activities. Biophysical studies indicate that optimally tuned mixtures exhibit greater disruption of synthetic lipid bilayers; however, their activity against more complex bacterial membrane compositions is largely unexplored. Herein, we applied electrochemical impedance spectroscopy (EIS) to investigate how two MG/FA pairs—composed of 10-carbon long monocaprin (MC) with capric acid (CA) and 12-carbon long glycerol monolaurate (GML) with lauric acid (LA)—disrupt tethered lipid bilayers composed of Escherichia coli bacterial lipids. While MC and CA individually inhibit E. coli, MC/CA mixtures at intermediate ratios displayed synergistic membrane-disruptive activity. Mechanistic studies showed that this synergistic activity depends on the MC/CA molar ratio rather than total lipid concentration. In contrast, GML/LA mixtures had weak membrane interactions across all tested ratios and lacked synergy, which is consistent with their low activity against E. coli. Together, the EIS results reveal that an effective disruption synergy against target membranes can arise from combining individually active antimicrobial lipids with distinct membrane-interaction profiles, laying the foundation to develop potent antimicrobial lipid formulations for tackling antibiotic-resistant bacteria. Full article

Layered graphene oxide (GO) has emerged as an ideal membrane structure for water desalination. In GO-stacked structures, the slit gaps between GO nanosheets can serve as critical pathways for molecule permeation. Exploring the permeation mechanisms of functionalized GO nanoslits is critical for improving the separation performance. Herein, molecular simulations were performed to investigate the water permeation and ion rejection for six types of ionic solutions by considering edge-amino functionalized GO (NGO) slit membranes. The NGO slit exhibits higher ion retention while maintaining reasonable water permeability. Edge amine groups can interact strongly with water molecules and immobilize ions, thus enhancing ion rejection. The thermodynamic free energy for ion passing was simulated to explain the unique ion rejection mechanism of amine-functionalized GO slits. The thermodynamic barrier for ion rejection can be considered as the delicate combination of the ion dehydration effect and the slit-generated attraction. The ion dehydration accounts for a repulsive contribution, which is the controlling portion in governing the free-energy profile. Overall, our work is important and valuable for the development and design of new-type layered GO membranes. Full article

Background: Anemoside B4 (AB4), the major bioactive saponin from Pulsatilla chinensis, exhibits anti-inflammatory, anti-tumor, anti-apoptotic, and analgesic properties. However, its clinical translation for ulcerative colitis (UC) is constrained by poor epithelial permeability and low oral bioavailability. Objective: This study’s objective was to engineer and optimize thermosensitive rectal in situ gels (ISGs) of AB4, incorporating suitable absorption enhancers to improve mucosal permeation, bioavailability, and therapeutic efficacy against UC. Methods: Screening of effective permeation enhancers was conducted using Caco-2 cell monolayers and Franz diffusion cells. Critical formulation variables such as poloxamer 407 (P407), poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC) were optimized, employing single-factor experiments coupled with the Box–Behnken design response surface methodology (BBD-RSM). Comprehensive characterization encompassed in vitro release kinetics, in vivo pharmacokinetics, rectal tissue tolerability, rectal retention time, and pharmacodynamic efficacy in a UC model. Results: We used 2.5% hydroxypropyl-β-cyclodextrin (HP-β-CD) and 1.0% sodium caprate (SC) as the appropriate absorption enhancers, and the amounts of P407, P188, and HPMC were 17.41%, 4.07%, and 0.44%, respectively, to yield the corresponding in situ gels HP-β-CD-AB4-ISG and SC-AB4-ISG. The gel characterization, such as gelation temperature, gelation time, pH, gelation strength, etc., was in accordance with requirements. The ISGs did not stimulate or damage rectal tissue and remained in the rectum for a prolonged period. More importantly, an improvement in bioavailability and alleviation of UC were noted. Conclusion: Absorption enhancer-assisted, poloxamer-based thermosensitive rectal ISGs provide a safe, convenient, and effective platform for targeted delivery of AB4 to the colorectum. This strategy addresses key limitations of oral dosing and warrants further clinical development for UC and related colorectal inflammatory diseases. Full article

This work presents the development and characterization of alumina–carbon black (ACB) composite membranes for enhanced hydrogen separation performance. A series of membranes containing 0–3.0 wt.% carbon black was fabricated via high-temperature sintering and systematically investigated with respect to their structural, morphological, mechanical, and gas separation properties. The addition of carbon black significantly influenced membrane microstructure, promoting pore network formation, increasing specific surface area, and enhancing gas transport. Gas permeation tests using H₂ and N₂ revealed that all ACB membranes exhibited higher hydrogen permeance than the pure Al₂O₃ membrane. Notably, the ACB3.0 specimen demonstrated the highest H₂ permeance of 508 × 10⁻⁶ mol m⁻² s⁻¹ Pa⁻¹ at 303 K, which is nearly four times greater than the unmodified membrane. At an elevated temperature (773 K), H₂/N₂ selectivity improved with increasing carbon black content, with ACB3.0 achieving a maximum selectivity of 3.82, exceeding the theoretical Knudsen value, suggesting a synergistic contribution of Knudsen diffusion and surface diffusion. These results demonstrate that carbon black is a cost-effective and versatile additive for modifying ceramic membranes, offering a promising route for advancing hydrogen purification technologies in industrial applications. Full article

Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers affecting the central nervous system (CNS), predominantly in adults. Despite significant advancements in this field, GB treatment still relies primarily on conventional approaches, including surgical resection, radiotherapy, and chemotherapy, which, due to its complex pathological characteristics, resistance mechanisms, and restrictive nature of the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), remain of limited efficacy. In this context, the development of innovative therapeutic strategies able to overcome these barriers, induce cancer cell death, and improve patient prognosis is crucial. Recently, nanoparticle platforms and focused ultrasounds seem to be promising approaches for cancer treatment. Nanoparticles enable targeting and controlled release, whilst focused ultrasounds enhance tissue permeation, increasing drug accumulation in a specific organ. However, nanoparticles can suffer from synthesis complexity, long-term biocompatibility and accumulation in the body with consequent toxicity, whereas focused ultrasounds require specialized equipment and can potentially cause thermal damage, hemorrhage, or cavitation injury. Cyclodextrins (CYDs) possess good properties and represent a versatile and safer alternative able to improve drug stability, solubility, and bioavailability, and depending on the type, dose, and administration route, can reduce local and systemic toxicity. Thus, CYDs emerge as promising novel excipients in GB treatment. Despite these advantages, CYD complexes suffer from receptor specificity, reducing their potential in precision medicine. By combining CYD complexes with polymeric or lipidic platforms, the advantages of CYD safety and drug solubilization together with their specific targeting can be obtained, thus enhancing selectivity and maximizing efficacy while minimizing recurrence and systemic toxicity. This review provides a comprehensive overview of GB pathology, conventional treatments, and emerging CYD-based strategies aimed at enhancing drug delivery and therapeutic efficacy. Full article

Objectives: Cyclosporin A (CsA) is an immunosuppressive drug that is highly effective. CsA, similar to other drugs with limited oral bioavailability due to poor membrane permeability, requires the use of absorption enhancers in its formulations. Phe-Cys-Ile-Gly-Arg-Leu (FCIGRL-OH), a peptide fragment of Zonula occludens toxin (ZOT), has been studied for its potential to enhance drug absorption by regulating intercellular tight junctions. This study aimed to evaluate the effects of four novel modified peptides, which have been substituted or dimerized at the C-terminus or cysteine moiety of FCIGRL-OH, as improved versions of FCIGRL-OH on the intestinal permeation of CsA. Methods: The four modified peptides used were FCIGRL-NH₂ (Pep-1), homo-dimer peptides derived from FCIGRL-OH and Pep-1 (Pep-2, Pep-3), and a peptide in which the cysteine in Pep-1 was replaced with N₃-substituted dipropionic acid (Pep-4). Pharmacokinetic analysis was performed following intraduodenal administration of CsA with each of four peptides in the presence of levan and benzalkonium chloride (BC) in rats. Results: Results showed that each of Pep-2, Pep-3, and Pep-4 significantly increased intestinal absorption of CsA in the presence of levan and BC. In particular, the area under the curve (AUC_0–360min) for CsA was significantly enhanced by 2.01-fold (p < 0.01) and 2.03-fold (p < 0.05) when treated with Pep-3 and Pep-4, respectively, at a dose of 10 mg·kg⁻¹. Additionally, the maximum plasma concentration (C_max) of CsA increased by 2.46-fold (p < 0.01) with Pep-3 and by 2.37-fold (p < 0.01) with Pep-4. Conclusions: These study findings indicate that Pep-2, particularly Pep-3 and Pep-4, are involved in tight junction opening as novel absorption enhancers for intestinal delivery of CsA. Full article