Formulation of plumbagin loaded long circulating pegylated liposomes: in vivo evaluation in C57BL/6J mice bearing B16F1 melanoma

Abstract

Context and Objective: Plumbagin (2-methyl, 5-hydroxy, 1, 4-naphthoquinone), an anticancer agent is encapsulated either as conventional or long circulating liposomal formulations to enhance its biological half-life and antitumor efficacy.

Methods: The liposomes were prepared by thin film hydration method and in vitro characterization was carried out to examine the particle size, zeta potential, drug encapsulation efficiency and in vitro release. The optimized formulations were tested for pharmacokinetic and pharmacodynamic efficacy against mice bearing B16F1 melanoma. Also in vivo toxicity studies were carried out.

Results and Discussion: The optimum particle size and entrapment efficiency was observed at drug to lipid molar ratio of 1:20. The in-vitro release of plumbagin from the liposomal formulations in phosphate-buffered saline (pH 7.4) showed biphasic release with an initial burst release followed by sustained release phase. Elimination half life (T_1/2) of pegylated, conventional and free plumbagin was 1305.76 ± 278.16, 346.87 ± 33.82 and 35.89 ± 7.95 min respectively. Further, plumbagin exhibited better antitumor efficacy in vivo when administered as long circulating liposomes with no signs of normal tissue toxicity.

Conclusion: It can be concluded that the pegylated liposomes could provide a promising parenteral platform for plumbagin with enhanced plasma half-life and therapeutic efficacy.

Keywords::

• Liposomes
• particle size
• pegylation
• in vitro release
• pharmacokinetics
• B16F1 melanoma

Acknowledgement

The financial support from Indian Council of Medical Research (ICMR), New Delhi, India (IRIS No: 2005-00150), to carry out this study is gratefully acknowledged. The authors are thankful to Dr. K. Satyamoorthy, Director, Manipal Life Sciences Centre, Manipal University, Manipal for providing the facilities and encouragement during this study. The authors are also thankful to Dr. Kanthi Latha Pai, Professor and Head, Department of Pathology, KMC International Centre, Manipal University, Manipal for her kind help in carrying out the histopathological toxicity studies.

Declaration of interest

The authors have no conflict of interest.