Carmustine loaded lactoferrin nanoparticles demonstrates an enhanced antiproliferative activity against glioblastoma in vitro

Abstract

Objective: Despite sophisticated treatment regimens, there is no significant improvement in the mortality rates of glioblastoma due to insufficient dosage delivery, reoccurrence of tumors, higher systemic toxicity, etc. Since brain endothelial cells and glioblastoma cells express lactoferrin receptors, a target-specific drug delivery vehicle was developed using lactoferrin itself as a matrix, into which carmustine was loaded. The objective was to use carmustine loaded lactoferrin nanoparticles (CLN) to achieve higher therapeutic efficacy and target specificity compared to free carmustine. Methods: CLN were prepared using the Sol-oil method. The nanoparticles prepared were characterized for their size, shape, polydispersity, and stability using FESEM and DLS methods. Drug loading and drug releasing efficiencies were also estimated. Further, cellular uptake of nanoparticles and their antiproliferative efficacy against glioblastoma cells were evaluated. Results: Characterization of CLN showed that they were spherical with ≤ 41 nm diameter and exhibited homogeneously dispersed stable distribution. Loading efficiency of carmustine in CLN was estimated to be 43±3.7 %. Drug release from the nanoparticles was pH dependent with the maximum observed at pH 5. At physiological and gastric pH, drug release was lower, whereas maximum release was observed at endocytotic vesicular and around tumor extracellular pH. Confocal microscopic studies showed an active cellular uptake of nanoparticles. Results of antiproliferative analysis substantiated a higher antiproliferative effect for CLN compared to free carmustine. Conclusion: The results of the study demonstrated that CLN serves as a vital tool, in designing an effective treatment strategy for targeted drug delivery to glioblastoma.