Development of a Nanoparticle-Embedded Chitosan Sponge for Topical and Local Administration of Chemotherapeutic Agents

Abstract

The following work describes the development of a novel noninvasive transmucosal drug delivery system, the chitosan sponge matrix (CSM). It is composed of cationic chitosan (CS) nanoparticles (NPs) that encapsulate cisplatin (CDDP) embedded within a polymeric mucoadhesive CS matrix. CSM is designed to swell up when exposed to moisture, facilitating release of the NPs via diffusion across the matrix. CSM is intended to be administered topically and locally to mucosal tissues, with its initial indication being oral cancer (OC). Currently, intravenous (IV) administered CDDP is the gold standard chemotherapeutic agent used in the treatment of OC. However, its clinical use has been limited by its renal and hemotoxicity profile. We aim to locally administer CDDP via encapsulation in CS NPs and deliver them directly to the oral cavity with CSM. It is hypothesized that such a delivery device will greatly reduce any systemic toxicity and increase antitumor efficacy. This paper describes the methods for developing CSM and maintaining the integrity of CDDP NPs embedded in the CSM.

In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems

“…25 Due to this strong electrostatic repulsion, CNPs prepared at more acidic CS pH are merely unstable and tend to form large particle size. 26 CS at pH 5 has less extended CS chain because of lower degree of amine protonation. Due to compact CS chain and weakened electrostatic repulsion, the formation of small CNP size is favored at this pH value compared to more extended CS structure.…”

A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer

“…To this end, a wide range of nanoparticles (NPs) based drug delivery systems (DDSs) have been explored as alternative cisplatin delivery methods that may promote its accumulation and retention in cancer cells and thus overcoming the low therapeutic ratio of the free drug 14 – 16 . While some of these NP formulations have demonstrated promising preclinical results, and a few have entered clinical trials, none have been approved for treatment of human cancers and only a few studies have tested the potential utilization of these approaches in head and neck cancer models 17 – 21 .…”

“…The difficulty of maintaining the delicate balance of extracellular stability and intracellular drug uptake remains a major barrier that hinders the application of polymeric cisplatin-loaded NPs in oncology. To overcome this challenge, we have encapsulated cisplatin within chitosan nanoparticles (a non-toxic, biocompatible, biodegradable polysaccharide derived from natural chitin 22 ) and embedded them within a chitosan sponge matrix (CSM) 17 . Such encapsulation protects cisplatin from biological deactivation and promotes increased rates of cell uptake 23 .…”

Nanocomposite sponges for enhancing intestinal residence time following oral administration

“…These observations were in agreement with the morphological evaluation and suggested that part of the NE was on the bulk of the membranes constituting the pores of the sponges, while part of the NE was located at the sponge surface (see figure 3). NE can interact with the CH polymer chains via hydrogen bonding and hydrophobic interactions, thanks to CH hydrophobicity (4% DA in the neutralized state) [52,53]. In the sponge at NE/CH ratio of 25, NE was present in excess at the surface and the sponge lost its porous nature, as highlighted by the SEM images (Fig.…”