Development of mucoadhesive drug carrier systems with quality by design approach

Parkinson's disease is a common neurodegenerative disease, and treatment approaches include examining alternative administration routes to existing neurotherapeutics. In intranasal route that provides great advantages in brain targeting of drugs, it is aimed to prolong the stay in the mucosa and increase penetration with mucoadhesive nanomaterials. Chitosan nanoparticles are mucoadhesive, non-toxic, biocompatible, biodegradable and can provide high drug loading capacity. Studies also found improved mucoadhesion properties for various chitosan derivatives. Quality by Design (QbD), a holistic methodology used in pharmaceutical development, enables determining process and formulation parameters that provide specific quality features through several stages. This study aims to develop a new mucoadhesive drug carrier nanoformulation can be administered nasally with DDK-DEGDA product, synthesized by the conjugation of an acrylate monomer diethylene glycol diacrylate (DEGDA) to deacetylated and depolymerized chitosan (DDK), from the QbD perspective. For this purpose, deacetylation and depolymerization processes were applied to chitosan (K), and DDK conjugated with DEGDA then the product (DDK-DEGDA) was characterized. Increased mucoadhesion examined in vitro using nasal mucosa and mucin was observed with DDK-DEGDA. DDK-DEGDA nanoparticles were prepared by ionic gelation with sizes smaller than 200 nm and 100 nm having suitable characteristics by different experimental designs. There were improvements in mucoadhesion of those with a size below 100 nm compared to K nanoparticles prepared in the same formulation. From drug loading studies, it was observed that 50% of L-DOPA was encapsulated in nanoparticles. The release profile of nanoparticles loaded with 0.2 mg and 0.4 mg L-DOPA was examined. In vitro cytotoxicity studies showed the nanoformulations were not toxic on the human neuroblastoma cell line (SH-SY5Y). In conclusion, it was seen that conjugation of K with DEGDA enabled the development of new mucoadhesive nanoformulations with appropriate size, distribution and zeta potential that can be used in the intranasal administration of the L-DOPA compound.