Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate

Background: Hydrogels are the polymeric network, which can retain large amount of water. Thus, these delivery systems always remained an issue of intensive research among the scientist fraternity. Objective: In this piece of work, we have reconnoitered the significance of the PEGylated anticancer loaded drug onto poloxamer based thermoresponsive injectable hydrogel to understand the role of delivery system. Method: To accomplish the objective, firstly it was necessary to improve the solubility of the melphalan, achieved by PEGylation of the drug with two grades of linear methoxy poly ethylene glycol (M-PEG), viz. M-PEG 2000 and 5000 Da to form a PEGylated melphalan conjugate (MLPEG). In our previous study, we have found that the prepared conjugates were efficiently enhanced the solubility of the melphalan and significantly reduced the hemolytic effect due to the presence of the PEG chains. Thus, in the present work, the prepared conjugates (MLPEG 5000 and 2000) were loaded to the thermosensitive Poloxamer 407 (P407) gel to produce an injectable hydrogel (MPX). To underline the reduction of the initial burst of the drug at the site of action, one of the hydrogels was prepared in the presence of the NaCl salt. Results: This in turn, tightened the PEO chains and remarkably reduced the drug’s initial burst from the delivery system as only 43 % of drug was released during 2 hours from MPX-CG hydrogel. Moreover, a lower diffusion coefficient (D) was noticed for MPX-CG gel as compared with MPX-7.4 gel. To confirm the depot formation, prepared hydrogels were administered to Wistar rats via subcutaneous and intramuscular routes. Conclusion: Thus, P407 based injectable hydrogel could play an important role for the delivery of a low dose-alkylating agent with reduced host cytotoxicity.