FORMULATION AND EVALUATION OF PARENTERAL METHOTREXATE NANOLIPOSOMES
Keywords:
Methotrexate, Liposomes, HSPC, Cholesterol, mPEG-DSPEAbstract
Objective: The objective of the present study was to encapsulate Methotrexate in liposomal formulation for treatment of cancer. Conventional compositions of Methotrexate are available but in high doses showvariation in bioavailability and they are associated with a number of toxicities when administered orally. To overcome these problems, in the present study, inclusion of Methotrexate in parenteral liposomal formulation was approached with the aim of increasing retention time at the site of action which leads to improvement in bioavailabilityand better tumor targeting.
Methods: In this study, PEGylated Methotrexate liposomes containing Hydrogenated Soy Phosphatidyl Choline and Cholesterol were prepared by thin film hydration method. The main advantage of PEGylated lipid vesicles lies in the possibility of active-targeted delivery of drugs to the tissues or organs that need those most. Attempts were made to enhance the encapsulation by use of non-ionic surfactants such as Tween-80, Tween-20 and solubilityenhancers such as β-cyclodextrin. The characterization of formulated liposomes was carried out by vesicle size, zeta potential, %free drug and in-vitro dissolution.
Results: Formulation containing 10mg/ml of Tween-20 and 20 mg/ml of β-cyclodextrin showed highest encapsulation efficiency. The optimized formulation has exhibited more than 90% release of the drug within a period of 4 days. The accelerated stability studies (40±2°C/ 75±5% RH) of the Methotrexate liposome were conducted for a period of three months and the formulation was found to be stable.
Conclusion: These results suggest that the liposome encapsulated MTX may serve as a useful targeted drug delivery system for effective management of neoplastic diseases.
Downloads
References
Noveen Konda, Arvind G, Sumit Shah, Prashanth P. Formulation and evaluation of non-pegylated doxorubicin liposomal drug delivery system. Int J Pharm Sci 2013;5:541-7.
Drummond DC, Meyer O. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 1999;51(4):691-743.
Lammers T, Hennink WE, Storm G. Tumour-targeted nanomedicines: Principles and practice. Br J Cancer 2008;99(3):392-7.
Chua SL, Rosenthal MA. Phase 2 study of temozolomide and caelyx in patients with recurrent glioblastoma multiforme. Neuro Oncol 2004;6(1):38-43.
Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylaed liposomal doxorubicin: review of animal and human studies. Clin Pharmacokinet 2003;42(5):419-36.
Sapra P, Allen TM. Ligand-targeted liposomal anticancer drugs. Prog Lipid Res 2003;42(5):439-62.
Pastorino F, Brignole C. Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy. Cancer Res 2006;66(20):73-82.
Saul JM, Annapragada AV, Bellamkonda RV. A dual-ligand approach for enhancing targeting selectivity of therapeutic nano carriers. J Control Release 2006;114(3):277-87.
Barca Maria. Comparative evaluation of methotrexate toxicity as solution for injection and liposomes following a short-term treatment in a Murine model of Arthritis. Farmacia 2013;61(1):220-28.
Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 1965;13:238–52.
Korsmeyer Rw, Gurny R. Peppas Mechanism of solute release from porous hydrophilic polymers, IJPS 1983;15:25-35.