Formulation of surface-functionalized hyaluronic acid-coated thiolated chitosan nano-formulation for the delivery of vincristine in prostate cancer: A multifunctional targeted drug delivery approach

Vincristine, a chemotherapeutic microtubule formation inhibitor, is used to treat all stages of prostate cancer. To enhance drug delivery at the specific site and increase the efficiency of sustained therapy, a targeted nanoformulation (NF) polymeric-based drug delivery approach with ligand surface modification was designed. The NF of thiolated chitosan (TC) coated with hyaluronic acid (HA) and loaded with vincristine (VC) by an ionic gelation process was synthesized and characterized. Insilico studies confirmed the attachment of HA with the CD44 receptor at binding sites A & B in prostate cancer cells. The zeta analysis showed an average particle size of 267.9 nm, PDI 0.210, and +15.1 zeta potential while FTIR confirmed the thiolated group in NF and Raman analysis confirmed the presence of hydrophilic groups, porous surface, and agglomeration features upon drug-polymer interaction. SEM and TEM showed spherical-shaped nanoparticles with smooth surfaces, whereas XRD confirmed the crystalline nature which makes NF very useful in targeted drug delivery systems. DSC confirmed the stability of NF at a high temperature greater than 100 °C. The drug loading and encapsulation efficiencies of the NF were 41.4 and 87% respectively, while the kinetics study of drug release showed that the NF followed the simple diffusion by the Higuchi square root of time equation in an acidic medium. The in vitro study showed sustained steady release at pH 7.4 and 6.8 up to 72 h As compared to short-term fast release in almost 12 h of conventional VC. The in vitro anticancer activity of the TCs-HA loaded with vincristine was checked by an MTT assay on normal prostate epithelial cells (HPrEC with IC50 of 16.2 μg/ml) and cancerous prostate cells (PC3 with IC50 of 32 μg/ml) at doses of 10–90 μg/ml in comparison to raw vincristine, which confirmed the strong cytotoxic potential of the prepared NF at lower doses and safety for normal prostate cells. All these properties enhance the sustainability, efficacy, and active targeting of NFs as a potent targeted therapeutic moiety in cancer treatment.