pH sensitive lipid polymeric hybrid nanoparticle (LPHNP) of paclitaxel and curcumin for targeted delivery in breast cancer.

Objective: The study aimed at designing a pH sensitive Lipid polymeric Hybrid nanoparticle (LPHNP) for targeted release of Paclitaxel (PTX) and Curcumin (CUR) in breast cancer.

Significance: Such systems shall result in controlled triggered release in acidic microenvironment of tumor cells with improved pharmacokinetic profile.

Methods: Chitosan-coated CUR and PTX coloaded pH-sensitive LPHNPs were synthesized employing nanoprecipitation technique. The synthesized NPs were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and morphology.

Results: LPHNPs co-loaded with curcumin (CUR) and paclitaxel (PTX) were successfully formulated, achieving a size of 146 nm, a PDI of 0.18, and an entrapment efficiency exceeding 90%. In vitro release studies demonstrated controlled release of CUR and PTX under tumor pH conditions showing 1.6 fold and 1.7 fold higher release in ABS pH 5 in comparison to PBS 7.4 for PTX and CUR respectively. MTT-assay studies revealed enhanced cytotoxicity of CUR and PTX as LPHNPs showing IC₅₀ value of free CUR & PTX 480.06 µg/mL decreasing to 282.97 µg/mL for CS-CUR-PTX-LPHNPs. In vivo pharmacokinetic evaluations in rats confirmed significantly improved bioavailability, with a 3.8-fold increase in AUC for CUR and a 6.6-fold increase for PTX. Additionally, the LPHNPs demonstrated controlled release and prolonged retention, evidenced by a 2.2-fold increase in the half-life (t1/2) of CUR and a 1.3-fold increase in the half-life of PTX.

The results underscores potential of chitosan-coated LPHNP as a promising delivery platform, offering high drug loading, optimal size for cellular penetration, and prolonged blood circulation for cancer.