Title:Lipid Based Aqueous Core Nanocapsules (ACNs) for Encapsulating Hydrophillic Vinorelbine Bitartrate: Preparation, Optimization, Characterization and In vitro Safety Assessment for Intravenous Administration
VOLUME: 15 ISSUE: 9
Author(s): Lakshmi, Sanjay Singh*, Mahalingam Rajamanickam Vijayakumar and Hitesh Kumar Dewangan
Affiliation:Department of Pharmaceutical Enginnering & Technology, Indian Institute of Technology (BHU), Varanasi, Department of Pharmaceutical Enginnering & Technology, Indian Institute of Technology (BHU), Varanasi, Department of Pharmaceutical Enginnering & Technology, Indian Institute of Technology (BHU), Varanasi, Department of Pharmaceutical Enginnering & Technology, Indian Institute of Technology (BHU), Varanasi
Keywords:Aqueous core nanocapsules, Box Behnken design, Vinorelbine bitartrate, hydrophilic drug, GMS nanocapsules,
transmission electron microscopy (TEM).
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.
