Functional shell engineering of bioactive wheat-seedling nanovesicles with chitosan derivatives for synergistic metabolic therapy via enhanced oral delivery.

PSS and its trimethyl chitosan coating multivesicular liposomes ameliorate transverse aortic constriction-induced cardiac hypertrophy.

Oral administration of polyelectrolyte modified curcumin-loaded egg protein nanoparticles for suppression of inflammation in colitis mice.

Inflammatory bowel disease (IBD) is persistent or recurrent intestinal inflammation. The severity of IBD is highly associated with an imbalance between M1 and M2 macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A scavenging ROS nanozyme, titanium carbide (Ti3C2), is synthesized to self-assemble with mannose-modified trimethyl chitosan to form nanoparticles (TTCM). The synthesized TTCM exhibits an excellent biocompatibility. Additionally, it remains stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). In vitro experiments show that TTCM significantly reduced ROS levels, restored mitochondrial membrane potential, increased superoxide dismutase (SOD) activity, and suppressed the TLR4/NF-κB pathway, hence promoting the repolarization of pro-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype. In addition, we found that TTCM amplified antioxidant efficacy when compared with Ti3C2. These effects enhanced the intestinal barrier. In vivo experiments utilizing a dextran sulfate sodium (DSS)-induced acute colitis mouse model revealed the anti-inflammatory and intestinal-barrier-protective effects of TTCM, effectively mitigating IBD progression. Consequently, the findings suggest that the oral delivery of ROS-scavenging nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for IBD treatment.

ABSTRACT The work reports the development of a polyelectrolyte complex (PEC) nanocomposite made up of trimethylchitosan (TMC), carboxymethyltamarind seed polysaccharide (CMTSP) and silver nanoparticles, as an effective matrix material for the sustained oral delivery of the anticancer drug 5‐Fluorouracil (5‐Fu). The experimental parameters have been optimized to achieve maximum yield of the PEC. The polymer materials made with different compositions were characterized using physicochemical characterization techniques. The swelling study of the developed matrix materials demonstrated pH‐responsive nature, with the materials exhibiting higher swelling at pH 7.4 than at pH 1.2. The in vitro release of the incorporated drug 5‐Fu from the matrix, evaluated under simulated gastric and intestinal conditions, revealed the pH‐dependent nature of the release. About 95.68 % of the entrapped drug was observed to be released from the nanocomposite at pH 7.4 over a period of 24 h, whereas only 52 % was released under pH 1.2 over a period of 4 h. The drug release process followed the first‐order kinetic model with a Fickian diffusion mechanism. The developed nanocomposite is shown to be compatible with MCF‐10A cell lines. Overall, the nanocomposite appears to be an ideal polymer matrix material for the effective sustained oral delivery of 5‐Fu in cancer therapy.

A review on chitosan-based delivery systems for vitamin B12: Advances, challenges, and future prospects.

Targeting inflammation and oxidative stress in experimental colitis through IL-6 siRNA and ascorbic acid co-loaded trimethyl chitosan nanoparticles.

Engineered nanoparticles for subconjunctival delivery to the retinal pigment epithelium: A multi-target therapy for dry AMD.

Surface functionalization of multilayer nanoparticles with hyaluronic acid or alternative polymers: Effects on cellular uptake and re-epithelialization in a human ex vivo wound model.

Alzheimer’s disease (AD) is a common neurodegenerative disorder with limited effective treatments. Cod skin collagen peptides (CSCPs) have neuroprotective potential for AD but face poor bioavailability—due to gastrointestinal enzyme cleavage and hepatic first-pass metabolism—prompting this study to develop a nanodelivery system to enhance CSCPs’ efficacy. Trimethyl chitosan (TMC)-based CSCP-loaded nanoparticles (CSCPs-NPs) were synthesized via ionic gelation, characterized for physicochemical properties, and tested in a D-galactose-induced AD mouse model (six groups: normal control, model, CSCPs low/high dose, blank NPs, CSCPs-NPs) using behavioral tests, histopathology, immunohistochemistry, and ELISA. CSCPs-NPs had a hydrodynamic diameter of 93.25 ± 21.52 nm, polydispersity index of 0.18 ± 0.13, 61.17% encapsulation efficiency, and sustained 24 h release. In AD mice, CSCPs-NPs significantly improved cognitive function and motor coordination, reduced hippocampal atrophy, preserved neurons, and mitigated oxidative stress, neuroinflammation, and apoptosis (upregulated Bcl-2, downregulated Bax)—effects matching high-dose free CSCPs. This TMC-based nanoformulation enhances CSCPs’ bioavailability and provides a promising strategy for AD intervention.

Though Curcumin (Cur) shows significant anti-cancer potential, its clinical utility is hindered by low bioavailability and rapid physiological clearance. These limitations hinder its effective use in pharmaceutical formulations, resulting in suboptimal therapeutic outcomes. To address this issue, a polyelectrolyte complex (PEC) of trimethylchitosan (TMC) and carboxymethylpectin (CMP) incorporated with silver nanoparticles (SNp) has been developed to be used as a matrix material for sustained release of Cur. The PEC nanocomposite, optimized for its composition, was characterized using sophisticated characterization techniques. Swelling studies indicated pH responsive nature of the PEC nanocomposite, with greater swelling at pH 7.4. The in-vitro drug release study indicated release of 35% of Cur in 4 h in the stomach environment (pH 1.2) and 79% in the intestinal condition (pH 7.4) in 24 h. In-vitro cytotoxicity analysis on MCF-10A cells demonstrated the biocompatible nature of polymer nanocomposite and cytotoxicity assay on MCF-7 cell lines proved the dose-dependent anti-cancer nature of the drug-loaded polymer matrix. The in-vitro degradability study demonstrated stability of the material towards degradation under physiological conditions. Overall, the developed PEC nanocomposite has been proved to be a promising oral drug delivery system for Cur with enhanced therapeutic efficiency.

Preparation and characterization of oral insulin-trimethyl chitosan complex-loaded solid self-nanoemulsifying drug delivery systems (SNEDDS).

Conventional intramuscular vaccines are unable to elicit robust mucosal immunity which is essential for preventing respiratory pathogens like SARS-CoV-2. To overcome this limitation, we developed an oral delivery platform based on coacervate formation (termed THT) through the electrostatic self-assembly of hyaluronic acid (HA) and trimethyl chitosan (TC) for the efficient oral delivery of adenovirus type 5-vectored COVID-19 vaccine (Ad5-nCoV) and protein antigens. THT coacervates shielded payloads from gastrointestinal degradation while simultaneously enhancing dendritic cell uptake and promoting dendritic cell maturation in vitro. Subsequent murine model studies demonstrated that oral vaccination with THT induced sustained systemic IgG and neutralizing antibody titers comparable to those achieved via intramuscular injection. Notably, this oral strategy uniquely elicited potent gut-mucosal secretory IgA responses, which was entirely absent in the intramuscular injection groups. The THT platform also generated durable memory T cell populations and spike-specific memory B cell reservoirs that persisted for over 180days post-boost. These cross-mucosal immune responses collectively conferred significant protection against SARS-CoV-2 virus challenge. Importantly, TC/HA coacervates similarly enhanced protein antigen immunogenicity, inducting robust humoral and mucosal immunity. Therefore, we established the THT coacervate as a highly promising and widely applicable oral platform to generate protective systemic and mucosal immunity against respiratory viral infections.

Multimodal chitosan-based materials for combination immunotherapy in cancers: Structural engineering, immune regulatory mechanisms and synergistic therapeutic applications.

Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown cardiac function benefits. Here, we designed a pH-responsive PSS-loaded nanoparticle drug delivery system. It was self-assembled by negatively charged PSS with positively charged trimethyl chitosan glycocholic acid (TMC-GA) via electrostatic interaction, and further stabilized the nanoparticles with Hydroxypropyl methylcellulose phthalate (HP55) excipients. The prepared TMC-GA/HP55@PSS nanoparticles were spherical, with a mean particle size of 361.5 ± 1.26 nm, zeta potential of −30.3 ± 0.9 mV, and encapsulation efficiency of 92.52 ± 2.4%. In vitro release study demonstrated the pH-responsive property of TMC-GA/HP55@PSS under intestinal conditions and facilitated nanoparticles absorption in the intestinal epithelium. In vitro experiments confirmed the biocompatibility of PSS and its ability to improve myocardial cell hypertrophy. In vivo, both PSS and its nanoparticles significantly ameliorated pressure overload–induced cardiac hypertrophy in mice, with TMC-GA/HP55@PSS exhibiting better cardioprotective efficacy. This study is the first to integrate pH-responsiveness and bile acid transport-mediated uptake into PSS nanocarrier systems. The findings provide valuable data and enlightenment for designing novel formulations and expanding the clinical applications of PSS.

Trimethyl chitosan: Antibacterial activity on Enterococcus faecalis biofilm and cytocompatibility on human periodontal ligament fibroblasts cells

This review explores the innovative use of trimethylated chitosan (TMC) nanoparticles in treating metastatic colon cancer (mCC). Conventional chemotherapy often faces challenges related to efficacy and safety, but TMC nanoparticles offer a promising alternative due to their biocompatibility, enhanced drug delivery, and potential to influence gene expression. The article examines how TMC nanoparticles improve the oral bioavailability of chemotherapeutics like 5-Fluorouracil and Irinotecan while also targeting cancer stem cells and the tumor microenvironment. Key findings suggest that TMC nanoparticles can effectively encapsulate genetic material, improve gene therapy outcomes while minimizing toxicity. Their ability to overcome biological barriers ensures the precise delivery of therapeutic agents to tumor sites, enhancing treatment effectiveness. The review also highlights the growing challenge of drug resistance and the need for personalized treatment approaches, emphasizing how TMC nanoparticles could play a crucial role in combination therapies. Future research directions include refining the design and synthesis of TMC nanoparticles, integrating artificial intelligence for personalized medicine, and identifying molecular targets. Overall, this review highlights the transformative potential of TMC nanoparticles in reshaping mCC treatment, offering more effective and targeted therapies that could significantly improve patient outcomes.

Cancer continues to be a major public health challenge due to therapeutic resistance, rising incidence and financial burden. Although anti-programmed cell death-ligand 1 (PD-L1) immunotherapy has revolutionised cancer treatment, its efficacy as monotherapy remains limited. Combining chemotherapy with immunotherapy offers the potential to amplify therapeutic outcomes and reduce side effects. Paclitaxel can induce immunogenic cell death (ICD) and improve tumour response to anti-PD-L1 therapy, thereby improving immunotherapy effectiveness. Meanwhile, small interfering RNA (siRNA) therapy can selectively suppress PD-L1 expression on the cell membrane and in the cytoplasm, though efficient delivery remains a challenge. We developed nanoparticles composed of trimethyl chitosan (TMC) and hyaluronic acid (HA) for delivering PD-L1 siRNA. These spherical nanoparticles (∼190 nm) demonstrated favourable physicochemical properties, high siRNA encapsulation efficiency, robust serum stability, a non-toxic nature and effective internalisation by cancer cells. The sequential therapy of sub-therapeutic doses of paclitaxel with siRNA PD-L1 in a 4T1 Balb/c mouse model compared to each monotherapy led to a substantial boost to antitumor immunity, suppression of tumour growth and increased infiltration of effector CD8+ T-cells within the tumour microenvironment. This study presents a novel siRNA delivery system and therapeutic approach that enhances the efficacy of breast cancer immunotherapy.

Formulation of siRNA nanoparticles, transfection and enhanced adhesion -penetration in nasal mucosal tissue.

Gene therapy using small interfering RNA (siRNA) holds promise for treating neurological disorders by silencing specific genes, like the phosphatase and tensin homolog (PTEN) gene, which restricts axonal growth. Effective siRNA delivery to neurons, however, poses challenges due to premature nucleic acid degradation and unspecific delivery. Chitosan-based delivery systems, noted for their biocompatibility, face limitations such as low transfection efficiency and lack of neurotropism. Building on the previous successes with neuron-targeted DNA delivery using chitosan, a novel approach for siRNA delivery aimed at PTEN downregulation is proposed. This involves using thiolated trimethyl chitosan (TMCSH)-based siRNA nanoparticles functionalized with the neurotropic C-terminal fragment of the tetanus neurotoxin heavy chain (HC) for efficient delivery to peripheral and central neurons. These polyplexes demonstrate suitable physicochemical properties, biocompatibility, and no adverse effects on neuronal electrophysiology. Diverse neuronal models, including 3D ex vivo cultures and microfluidics, confirm the polyplexes' efficiency and neurospecificity. HC-functionalization significantly enhances neuronal binding, and live cell imaging reveals fivefold faster retrograde transport along axons. Furthermore, siRNA delivery targeting PTEN promoted axonal outgrowth in embryonic cortical neurons. In conclusion, the proposed polyplexes represent a promising platform for neuronal siRNA delivery, offering potential for clinical translation and therapeutic applications.