Abstract

Background: Vinorelbine bitartrate (VRL) is an antimitotic agent approved by FDA for breast cancer and non-small cell lung cancer (NSCLC) in many countries. However, high aqueous solubility and thermo degradable nature of VRL limited the availability of marketed dosage forms.

Objectives: The current work is focused on the development of lipid based aqueous core nanocapsules which can encapsulate the hydrophilic VRL in the aqueous core of nanocapsules protected with a lipidic shell which will further provide a sustained release.

Methods: The ACNs were prepared by double emulsification technique followed by solvent evaporation. Box Behnken Design was utilized to optimize the formulation and process variables. Thirteen batches were generated utilizing lipid concentration, surfactant concentration and homogenizer speed as dependent variables (at three levels) and particle size and encapsulation efficiency as critical quality attributes. The ACNs were characterized for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, morphology by Transmission Electron Microscopy (TEM) and in vitro release. The ACNs were further evaluated for safety against intravenous administration by haemocompatibility studies.

Results: Results demonstrated that lipidic nanocapsules enhanced the entrapment efficiency of VRL up to 78%. Transmission Electron Microscopy revealed spherical shape of ACNs with core-shell structure. The GMS-VRL-ACNs showed that release followed Korsemeyer peppas kinetics suggesting Fickian diffusion. Moreover, the compliance towards haemocompatibility studies depicted the safety of prepared nanocapsules against intravenous administration.

Conclusion: ACNs were found to be promising in encapsulating high aqueous soluble anticancer drugs with enhanced entrapment and safety towards intravenous administration.

Keywords: Aqueous core nanocapsules, Box Behnken design, Vinorelbine bitartrate, hydrophilic drug, GMS nanocapsules, transmission electron microscopy (TEM).

Graphical Abstract