Eudragit S100-coated microbeads of thiolated chitosan/casein for pH-responsive colon-targeted delivery of 6-mercaptopurine

QbD-Optimized CD44-Targeted Hyaluronic Acid Chitosan Nanoparticles in Dual pH-Responsive Capsules for Colon-Directed Oral Delivery of 5-Fluorouracil

Chitosan-PLGA biopolymeric nanogel as a platform for enhanced methotrexate delivery and redox-modulated anti-inflammatory activity.

Methotrexate (MTX) is an effective disease-modifying antirheumatic drug for the treatment of chronic inflammatory disorders; however, its clinical application is limited by poor bioavailability, rapid systemic clearance, and dose-dependent adverse effects. In this study, a pH-responsive methotrexate-loaded chitosan/poly(lactic-co-glycolic acid) ((Chit/PLGA)/MTX) nanogel was developed to improve drug delivery and therapeutic performance. The nanogel was fabricated by ionic gelation followed by gamma radiation-induced in situ free-radical polymerization (20 kGy) and subsequently loaded with methotrexate using a pH-triggered swelling-shrinking encapsulation strategy. Physicochemical characterization by TEM, DLS, FTIR, UV-Vis spectroscopy, and zeta potential analysis confirmed the successful formation of spherical nanogel particles with an average hydrodynamic diameter of 125 nm, a polydispersity index of 0.18 ± 0.03, and a zeta potential of -2.5 mV. The nanogel exhibited a high encapsulation efficiency (89.3 ± 2.1%) and drug-loading capacity (15.1 ± 0.8%). In vitro release studies demonstrated pronounced pH-responsive behavior, with cumulative methotrexate release reaching approximately 60% at pH 5.5 compared with 40% at pH 7.4 after 300 s, indicating preferential drug release under acidic inflammatory conditions. Cytotoxicity evaluation showed that the nanogel formulation exhibited improved biocompatibility (IC₅₀ = 422.5 μg/mL) compared with free methotrexate (IC₅₀ = 311.7 μg/mL). The (Chit/PLGA)/MTX nanogel significantly enhanced antioxidant activity, exhibiting 79.1% DPPH radical scavenging, 81.8% membrane stabilization, and 83.3% inhibition of protein denaturation. Furthermore, the formulation effectively suppressed the expression of major inflammatory mediators, including COX-2 (37.2%), iNOS (47.2%), TNF-α (40.3%), and NF-κB (40.9%), while reducing IL-1β (33.5%) and IL-6 (45.0%) production. Collectively, these findings demonstrate that the pH-responsive Chitosan-PLGA nanogel provides efficient methotrexate encapsulation, controlled drug release, enhanced antioxidant activity, and potent anti-inflammatory effects, highlighting its promise as a nanocarrier platform for the treatment of chronic inflammatory diseases.

Nilotinib Tartrate Encapsulated Polycaprolactone Polymeric Nanoparticle Fabricated With Lactoferrin for the Treatment of Colorectal Cancer: In-Silico and In-Vitro Investigation

Dual-Layered, pH-Responsive PLGA-Based Nanocarriers for Enhanced Niclosamide Delivery and Anticancer Activity.

The clinical translation of niclosamide as an anticancer drug remains as a significant challenge mainly due to its poor aqueous solubility. To address this, a dual layered nanocarrier system, PLGA@Na-CMC-CaCO3 was developed in which the presence of PLGA enhanced the encapsulation of niclosamide, Na-CMC improved the bioavailability, and CaCO3 nanoparticles helped in pH-responsive drug release. The fabricated nanocarrier exhibited a uniform size with low polydispersity index when analyzed using DLS. The stepwise incorporation of all the elements along with the drug was confirmed using FTIR and XRD, and the thermal stability of the nanocarrier was assessed using TGA. The PLGA@Na-CMC-CaCO3 nanocarrier system demonstrated a high niclosamide encapsulation efficiency of ∼95.67%. Further a pH-dependent drug release profile was observed, with increased drug release under acidic pH mimicking the tumor microenvironment. The release kinetics followed the first-order and Higuchi models, confirming diffusion-dependent drug release. In vitro biological studies on MDA-MB-231 cells using the alamar blue assay demonstrated negligible cytotoxicity of PLGA@Na-CMC-CaCO3 nanocarriers alone, indicating their biocompatibility. In contrast, niclosamide-loaded PLGA@Na-CMC-CaCO3 nanocarriers showed enhanced dose-dependent cytotoxicity compared to niclosamide alone. The presence of apoptosis in niclosamide-loaded PLGA@Na-CMC-CaCO3 nanocarriers was confirmed by the JC-1 assay, which clearly demonstrated a dose-dependent decrease in mitochondrial membrane potential in the drug encapsulated nanocarrier system. Overall, this PLGA@Na-CMC-CaCO3 nanocarrier system has the potential to effectively address the key limitations of niclosamide delivery for improved cancer therapy.

Phytotherapeutics self-microemulsifying systems in pellet dosage form for enhanced intestinal drug delivery: formulation, stability, and in-vivo performance

Abstract Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120  min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5  mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67  ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.

Linoleic acid-based pH-sensitive 5-ASA nanocubosome pellets for colon targeting in ulcerative colitis: in vitro and in vivo comparison with non-pH-sensitive and conventional formulations.

OBJECTIVE This study aimed to design and evaluate pH-sensitive pellets loaded with 5-aminosalicylic acid (5-ASA) for targeted colon delivery in ulcerative colitis (UC) therapy. SIGNIFICANCE The proposed formulation leverages glyceryl monooleate (GMO) and linoleic acid (LA) as liquid crystal precursors to achieve site-specific drug release. METHODS Liquid crystal nanoparticles (LCNPs) were prepared from a GMO bulk phase using a top-down method, with LA added for pH sensitivity. The formulations were then evaluated for drug loading, encapsulation efficiency, and structure by polarized light microscopy, with drug release tested at pH 1.2 and 6.8. The LCNPs dispersions were then used to make pellets using the extrusion-spheronisation technique. Drug-excipient interactions were examined by FTIR and DSC. The pellet formulations were finally tested in a rat ulcerative colitis (UC) model by comparing colon damage scores across treatment groups. RESULTS The pH-sensitive pellets containing LCNPs exhibited a uniform morphology, desirable aspect ratio, and sufficient mechanical strength. The in vitro release profile demonstrated a 5.7-fold higher drug release at pH 6.8 compared to pH 1.2. This targeted release was ascribed to a pH-triggered phase transition of the LA and electrostatic repulsion between the ionized drug and the carrier. The in vivo results confirmed that the pH-sensitive pellets elicited the most pronounced and statistically significant (p < 0.05) reduction in colon damage scores. CONCLUSION The developed pellet system, which encapsulates 5-ASA within GMO/LA-based liquid crystal nanoparticles, presents a highly promising platform for targeted drug delivery in the treatment of ulcerative colitis.