Oral delivery of topotecan in polymeric nanoparticles: Lymphatic distribution and pharmacokinetics

There have been many attempts to formulate a variety of drugs in nano-size formulations. However, biodistribution characteristics of these formulated drugs remain unclear. Information about the pharmacokinetics and distributions of these formulations is essential for future practical use and advanced formulation development. Topotecan is a useful agent for treating a variety of cancers. It exhibits anti-cancer activity by inhibiting topoisomerase. However, oral bioavailability of topotecan was not satisfactory in previous studies. Reversible hydrolysis of its active site according to pH environment was a major limitation in terms of treatment. To improve the bioavailability and retention of topotecan in target organs (such as lung and brain) and increase its delivery to the lymphatic system as a major pathway for cancer metastasis, this study was conducted on topotecan-loaded nanoparticles using poly(lactic-co-glycolic acid) (PLGA). These nanoparticles were prepared by double emulsion solvent evaporation. Formulated topotecan-loaded PLGA nanoparticles were subjected to several in vitro tests to determine various physicochemical properties such as size, zeta potential, encapsulation efficiency, morphology, and release profile. These nanoparticles were also subjected to in vivo studies using rats. Based on in vivo results, pharmacokinetic properties, distribution in the body, and delivery efficiency of these formulated nanoparticles were confirmed. Topotecan-loaded PLGA nanoparticles showed a delayed release pattern in vitro. Their pharmacokinetic profiles and distributions in the body were clearly different from those of free topotecan hydrochloride. Results confirmed that topotecan encapsulated in the PLGA polymer was stable from hydrolysis and present in an active form for a longer time in the body. Biometric imaging revealed in vivo properties of topotecan-loaded PLGA nanoparticles for qualitative confirmation. And oral delivery of topotecan in polymeric nanoparticles to lymph and various body tissues has been identified. Findings of this study indicate that topotecan formulated into nanoparticles (using PLGA) has a better pharmacokinetic profile and a better delivery to lymphoid tissues, lung, and brain than free topotecan hydrochloride, suggesting that these topotecan-loaded PLGA nanoparticles might provide better therapeutic results.