Thermosensitive injectable hydrogel containing carboplatin loaded nanoparticles: A dual approach for sustained and localized delivery with improved safety and therapeutic efficacy

Abstract Novel formulation using a dual approach of nanoparticles-loaded in situ hydrogel to overcome the severe toxicity associated with conventional intravenous formulations like high systemic toxicity, frequent dosing, burst release, non-specific distribution, and poor therapeutic efficacy was developed. Carboplatin-loaded ethyl cellulose nanoparticles were prepared using double emulsion solvent evaporation method and characterized for size (213.8 ± 2.5 nm), shape and encapsulation efficiency (52.24 ± 3.1%). Optimized nanoparticle incorporated within in situ hydrogel base sustained the drug release for 7 days (94.53 ± 0.91%) whereas, pure drug and commercial counterpart showed burst release within 2 h. Further, rheology studies confirmed the formation of hydrogel at 37 ± 0.13 °C. Furthermore, ex vivo (hemolytic and cytotoxicity) and in vivo toxicity studies demonstrated better safety and tolerance of developed hydrogel in comparison to commercial. Pharmacokinetic and biodistribution studies showed the localized and sustained release behaviour of optimized formulation (MRT- 20.3 ± 1.01 h) in comparison to its commercial (MRT- 7.8 ± 0.3 h). In addition, good anti-tumor activity of hydrogel was also observed as evaluated using ehrlich ascitic carcinoma mice model. Thus, developed in situ hydrogel could be a safe and efficient delivery system for sustained and localized delivery of carboplatin and improved patient compliance.