Unlocking the Potential of Novel Hybrid Lipid Polymer Nanoparticles in Redefining Camptothecin Delivery: Achieving Controlled Release, Enhanced Cytotoxicity, and Improved Pharmacokinetics for Colorectal Cancer Therapy

In the field of oncology, addressing the key challenge of targeted and efficient anticancer drug delivery, this investigation highlights the novel development of core-shell hybrid lipid-polymer nanoparticles for camptothecin (CPT) delivery in colorectal cancer treatment. Unlike conventional delivery systems, the hybrid design integrates the stability of polymers with the biocompatibility of lipids, creating a unique platform with enhanced control over drug release and cellular uptake. A three-level factorial design was employed, offering a rigorous and systematic approach to explore the impact of key variables: polymer concentration, and lipid concentration on particle size and encapsulation efficiency. The optimized CPT-encapsulated hybrid systems with DSPE-mPEG2000 and poly (D, L-lactide-co-glycolide) demonstrated spherical morphology with mean particle size of 143 ± 0.7 nm, 91 ± 1.65 %w/w encapsulation efficiency, and a zeta potential of – 29 ± 0.16 mV. In vitro drug release studies revealed a pH-triggered profile, with slower release at physiological pH (7.4) than at tumor-relevant pH (5.5), suggesting targeted release in tumor environments while maintaining stability in the systemic circulation. Cytotoxicity assays on the SW-620 adenocarcinoma cell line revealed significantly enhanced cancer cell cytotoxicity and cellular uptake of CPT-loaded nanoparticles compared to the free drug solution. Furthermore, the in vivo pharmacokinetic study of nanostructures in rats demonstrated enhanced plasma drug concentration and retention time with reduced clearance as compared to free drug. The findings of the current investigation thus emphasize the potential of hybrid lipid-polymer nanoparticles as an innovative, adaptable platform for targeted, effective and selective treatment options for colorectal cancer. [Display omitted] •The development of hybrid lipid polymer nanoparticles was performed by modified rapid nanoprecipitation approach.•Optimization of HLPNs was executed through a three-level (32) factorial design.•The hybrid structure allows for better encapsulation of camptothecin, improving solubility and stability.•Increased cytotoxicity and cell uptake against SW-620 CRC cell lines with CPT-loaded HLPNs formulation compared to free drug thereby reducing side effects.•Enhanced in vivo pharmacokinetic parameters such as t1/2, AUC, MRT indicated prolonged blood circulation.