Formulation of polysaccharide-based nanoparticles for local administration into the oral cavity

Abstract

The efficacy of treatments for oral ailments is often challenged by a low residence time of the conventional pharmaceutical formulations in the oral cavity. The residence time in the oral cavity could be improved by using bioadhesive formulations, such as preparations based on polysaccharides. This study describes the formulation and the evaluation of polysaccharide-based nanosystems as drug delivery systems addressed to the oral cavity. Nanoparticles based on chitosan, alginate or pectin were prepared through self-assembly by ionotropic gelation using oppositely charged crosslinkers (tripolyphosphate or zinc). Characteristics of nanoparticles at increasing crosslinker concentration provided the basis for selecting the most suitable formulations. The nanoparticles were tested for cytotoxicity against buccal cells (TR146) and for stability in a medium simulating pH, ionic strength, electrolyte composition and concentration of saliva. Alginate nanoparticles were the most stable in the salivary environment, while chitosan nanoparticles were the most cytocompatible. Alginate nanoparticles and pectin nanoparticles revealed possible cytotoxicity due to the presence of zinc. This knowledge is important in the early design of polymer-based nanoparticles for oral usage and for potential improving of the biocompatibility of the investigated nanoparticles with the oral environment.

An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery

“…In vitro cytotoxicity of chitosan based NP against buccal cells (TR146) was evaluated by Pistone et al [79]. Three types of NP were prepared; alginate, Zn +2 —crosslinked pectin NP and chitosan NP crosslinked with TPP.…”

Cell culture models of oral mucosal barriers: A review with a focus on applications, culture conditions and barrier properties

“…71 Concretely, TR146 cells are frequently applied to study the effect of permeability enhancers like chitosan, 72,74 bile salts like sodium glycocholate 65 or amino acids 75 on drug transport. TR146 cells were recently used for the evaluation of nanosystems 76,77 and for cytotoxicity studies of bioadhesive hydrogels for buccal drug delivery. 78 Approaches that have shown promising effects in enhancing transport of macromolecules in several in vitro and in vivo buccal model systems have been extensively reviewed previously.…”

Essential oil loaded pectin/chitosan nanoparticles preparation and optimization via Box–Behnken design against MCF-7 breast cancer cell lines

“…1 Natural polysaccharides such as chitosan (CS) and pectin (Pec) are frequently utilized in pharmaceutical formulations due to their biodegradability and biocompatibility advantages. 3 Pec is a polyanion with a large number of poly-D-galacturonic acid residues linked via a-1,4-glycosidic bonds. 4 CS on the other hand is a polycation, consisting of linear chains of glucosamine and N-acetyl-D-glucosamine with intrinsic antimicrobial properties.…”