Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

Chitosan is a naturally derived polymer with biocompatible and mucoadhesive properties, making it a candidate for drug delivery systems. While prior research has demonstrated its ability to promote cellular uptake, gaps remain in understanding how chitosan nanoparticles (NPs) behave at the biological interface. Established knowledge includes chitosan's positive charge and proton sponge effect, which facilitate endosomal escape. However, the full extent of its interactions with cells and tissues has not been fully characterized. This uncertainty drives the need to explore how chitosan NPs are internalized and transported within cells. No prior work has resolved how administration routes and surface modifications influence biodistribution and targeting. Understanding these mechanisms is essential for optimizing chitosan-based drug delivery systems. The current literature lacks a comprehensive review of chitosan's behavior in vivo and in vitro. This gap motivates the need for a synthesis of recent findings to guide future applications.

This review aims to evaluate how chitosan's physical and chemical properties influence its performance in drug delivery systems. The primary goal is to clarify how chitosan nanoparticles interact with cells and biological compartments. Researchers sought to analyze recent studies on chitosan's behavior during cellular uptake and intracellular transport. The motivation stems from the need to improve targeting and bioavailability of chitosan NPs. The study focuses on mechanisms such as endosomal escape and serum protein corona formation. The authors propose that understanding these interactions can lead to better design of chitosan-based formulations. The review also examines how administration routes and surface modifications affect biodistribution. This work addresses a gap in the literature by providing a comprehensive overview of chitosan's biological behavior.

The authors conducted a literature review of recent studies on chitosan nanoparticle interactions with cells and tissues. They analyzed findings related to cellular uptake mechanisms and intracellular trafficking. The review approach included examining how chitosan's positive charge facilitates cell attachment. The researchers also assessed the proton sponge effect and its role in endosomal escape. They evaluated in vivo studies on biodistribution and serum protein corona formation. The synthesis of evidence focused on how administration routes influence RES uptake. The authors compared different surface modification strategies to improve targeting. The review approach included summarizing clinical trials and toxicological studies.

Chitosan nanoparticles are internalized via multiple pathways, including endocytosis and phagocytosis. The proton sponge effect allows chitosan NPs to escape endosomal degradation. In vivo studies show that chitosan NPs are rapidly surrounded by a serum protein corona. Biodistribution is primarily to the liver and spleen, indicating RES uptake. Surface modifications can enhance targeting and bioavailability of chitosan NPs. Specific administration routes influence RES evasion and tissue distribution. Clinical trials suggest chitosan formulations have potential for pharmaceutical applications. The positive charge of chitosan enhances cell attachment and uptake efficiency.

The authors propose that chitosan's properties can be tuned to improve drug delivery performance. The synthesis of findings suggests that surface modifications and administration routes are key factors. The proton sponge effect is a critical mechanism for endosomal escape. Serum protein corona formation affects biodistribution and targeting. Clinical trials indicate chitosan's potential for therapeutic applications. The authors suggest that further research is needed to optimize formulation strategies. The findings highlight the importance of understanding chitosan's interactions at the biological interface. The review supports the need for continued toxicological evaluation of chitosan-based systems.