Dimeric camptothecin derived phospholipid assembled liposomes with high drug loading for cancer therapy

Schematic illustration of amphiphilic dimeric camptothecin glycerophosphorylcholine (di-CPT-GPC) prodrug for the self-assembly and delivery to tumor cell via endocytosis. [Display omitted] •Dimeric camptothecin phospholipid assembled liposomes have high drug loading.•The liposomes release parent CPT sustainably in a weakly acidic environment.•The liposomes have favorable anticancer activity both in vitro and in vivo.. In this study, a newly liposomal formulation of camptothecin (CPT) based on the dimeric camptothecin glycerophosphorylcholine (di-CPT-GPC) prodrug was developed. The di-CPT-GPC prodrug was synthesized through the heterogeneous conjugation of camptothecin-20 succinate with glycerophosphorylcholine. It undergoes assembly to form liposomes without any excipient through the thin film hydration method, which, confirmed by dynamic light scattering (DLS), have an average diameter of approximately 165 ± 5 nm. Observations on cryogenic transmission electron microscopy (cryo-TEM) demonstrated that the liposomes possess a typical multilamellar vesicle structure with a bilayer thickness of approximately 4 nm. The liposomes with a CPT loading up to 62 wt% maintained good stability in simulated physiological fluid. This can be attributed to the protection of the liposomes having CPT groups sequestered within the bilayer interior. Moreover, the in vitro release behavior of di-CPT-GPC liposomes was monitored using different media. The results showed that the liposomes could dissociate and sustainably release free active form CPT in a weak acidic environment. In vitro anticancer activity tests indicated that di-CPT-GPC liposomes had comparable cytotoxicity to the parent drug against MCF-7, HeLa and HepG-2 cells. Finally, a preliminary in vivo antitumor evaluation revealed that the liposomes inhibited tumor growth. Taken together, the di-CPT-GPC assembled liposomes with high drug loading could be a promising nanoformulation of CPT.