Background: Vinorelbine bitartrate (VRL), a semi synthetic vinca alkaloid approved for
breast cancer, has been proven to be beneficial as first line and subsequent therapies. However, its hydrophilic
and thermo labile nature provides hindrance to oral clinical translation.
Objectives: The current work focused on the application of DOE a modern statistical optimization tool
for the development and optimization of a solid lipid nanoparticle (SLN) formulation that can encapsulate
hydrophilic and thermolabile Vinorelbine bitartrate (VRL) to a maximum extent without compromising
integrity and anticancer activity of the drug.
Methods: SLNs were prepared by solvent diffusion technique employing Taguchi orthogonal array
design with optimized formulation and process variables. The emulsifying nature and low melting point
of glyceryl mono-oleate (GMO) were exploited to enhance entrapment and minimizing temperature
associated degradation, respectively. Moreover, two types of surfactants, Vitamin E TPGS (TPGS) and
Poloxamer-188 were utilized to obtain TPGS-VRL-SLNs and PL-VRL-SLNs, respectively. The SLNs
were characterized for various physicochemical properties, in-vitro drug release kinetics and anticancer
activity by MTT assay on MCF-7 cancer cell lines.
Results: The SLNs were found to be spherical in shape with entrapment efficiency (EE) up to 58 %. Invitro
release studies showed biphasic release pattern following Korsemeyer peppas model with fickian
release kinetics. Results of MTT assay revealed that TPGS-VRL-SLNs and PL-VRL-SLNs were 39.5
and 18.5 fold more effective, respectively, compared to the pristine VRL.
Conclusion: DOE approach was successfully applied for the development of VRL-SLNs. Enhanced
entrapment and anticancer efficacy of TPGS-VRL-SLN can be attributed to emulsifying nature of GMO
and inherent cytotoxic nature of TPGS, respectively, which synergizes with VRL. Therefore, TPGS
associated SLNs may be potential carrier in cancer chemotherapeutics.