FORMULATION AND QBD BASED OPTIMIZATION OF METHOTREXATE-LOADED SOLID LIPID NANOPARTICLES FOR AN EFFECTIVE ANTI-CANCER TREATMENT

Chaitali Surve,Srinivas Patnaik,Ananya Banerjee,Supriya Shidhaye,Ruchi Singh

doi:10.22159/ijap.2021v13i5.42373

Abstract

Objective: In the current study, the Quality by Design method was utilized for the formulation of solid lipid nanoparticles of Methotrexate (MTX SLNs). Methods: MTX SLNs formulated by melt emulsification method were studied for the effect of independent variables viz. concentration of lipid and surfactants on quality attributes viz. particle size, polydispersity index, and entrapment efficiency of SLNs using 32 factorial design. Results: The optimal formulation was spherical, had a particle size of 147.6±4.1 nm (z-average), a polydispersity index of 0.296±0.058, a zeta potential of −19±0.98 mV, encapsulation efficiency of 98.7±1.55%, and a cumulative drug release of 95.59±0.918% in 5 h. Conclusion: The in vitro and in vivo studies revealed that SLNs provide a promising oral delivery system to improve the bioavailability of MTX.

Highlights

Methotrexate (N-[4-[[(2, 4-Diamino-6-pteridinyl) methyl] nmethylamino] benzoyl]-L-glutamic acid or 4-Amino-N10-methylpteroyl-L-glutamic acid)(MTX) is used in the management of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides, nonHodgkin’s lymphomas, and lung cancer
Various studies suggest that solid lipid nanoparticles (SLNs) formulations with a blend of surfactants display higher kinetic stability with a lower particle size as opposed to formulations prepared by the use of one surfactant [12]
When sonication time was increased up to 12 min (Batch no.15, table 2b) there was no further significant change in particle size, polydispersity index (PDI) and %EE. This could be because the higher kinetic energy provided by the sonication process could not contribute to the lowering of size and PDI further since even the lipid center is already shaped with lower size and PDI

Summary

Introduction

Methotrexate (N-[4-[[(2, 4-Diamino-6-pteridinyl) methyl] nmethylamino] benzoyl]-L-glutamic acid or 4-Amino-N10-methylpteroyl-L-glutamic acid)(MTX) is used in the management of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides, nonHodgkin’s lymphomas, and lung cancer. It inhibits dihydrofolate reductase, thymidylate synthase, and 5-aminoimidazole carboxamide ribotide transformylase [1]. Several drug delivery strategies such as liposomes, nanocapsules and nanoparticles, polymer-drug conjugates, and polymeric micelles have been employed to improve the effectiveness of anticancer agents [4,5,6,7,8,9]. SLNs can help in reducing the dose and dose frequency, improving patient compliance, and delaying the onset of resistance [10,11,12]

Methods

Results

Conclusion