Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Abstract

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico–chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

“…The nanocarrier was coated with chitosan of different molecular weights to evaluate its effect on drug permeability in RPMI 2650 human nasal cell line. The results revealed ten times more permeation of the drug when low molecular weight chitosan was used and 6.5 times higher penetration when high molecular weight was employed, compared to uncoated nanocapsules [51]. Likewise, another work using PCL nanoparticles loaded with docetaxel to brain cancer found higher cytotoxicity with chitosan-decorated nanoparticles compared to the free docetaxel [87].…”

“…The superficial modification with chitosan can be performed through the generation of new covalent bonds or by non-covalent interactions between the chemical groups present in the nanoparticle materials and chitosan molecular chains ( Figure 2) [51]. The chitosan coating architecture is influenced by the method of preparation, the type of chitosan, and the molecular properties of the nanoparticle´s materials; thus, the choice of the correct mechanism will lead to better results.…”

“…The emulsion still hot is transferred to a chitosan solution (0.2%) with acetic acid (1%) at 4 • C, instead of cold water. Another modified method is the interfacial deposition of pre-formed polymers to obtain lipid core polymeric nanocapsules, where the aqueous phase contains chitosan at 0.1% [51].…”

The Design of Poly(lactide-co-glycolide) Nanocarriers for Medical Applications

“…Chitosan, a natural polymer that is formed by partial deacetylation of chitin, is also commonly grafted onto the surface of PLGA based systems to increase biocompatibility. It is biodegradable and has mucoadhesive properties as it carries a positive charge and can efficiently bind to negatively charged cell membranes (Bruinsmann et al, 2019). Hence, a coating of chitosan on the PLGA nanostructure shields it from opsonins and promotes stronger cellular interaction and retention (Lima et al, 2018).…”

Microfluidic Synthesis of Vinblastine-Loaded Multifunctional Particles for Magnetically Responsive Controlled Drug Release

“…In addition, functional drug carriers could be obtained by combining NPs with polymers. Herein, we designed a magnetically responsive functional drug carrier by loading SPIO NPs in a chitosan polymer [33]. The magnetically responsive drug formulation was prepared with a uniform particle size by using a microfluidic chip, and it was further applied in the controlled VBL drug release study.…”