Alginate-based ‘nano-micro’ hybrid matrices developed using ultrasonic atomization for Co-delivery of chemotherapeutic drugs against superficial tumors

Abstract

Cancer has remained a life-threatening condition, with about 9.6 million deaths globally, despite the advancements and research in therapeutic approaches. Several chemotherapeutic agents are available which can reduce the size of tumors but have non-specific adverse effects on surrounding cells and the propensity to cause the formation of multi-drug resistant tumors. This report investigates a novel and facile method of ultrasonic atomization for the synthesis of Doxorubicin (Dox) loaded chitosan and Piperine (Pip) loaded Poly lactide-co-glycolide (PLGA) nanoparticles (Dox-Ch-NP, Pip-PLGA-NP). Further co-encapsulate these drug-loaded nanoparticles in hybrid alginate microspheres (HAM) using the same technique. The nanoparticles and microspheres were analyzed for size and morphology by DLS, SEM, TEM and CLSM. In vitro studies were performed to determine encapsulation efficiency, drug release and cell cytotoxicity. For the in-vivo evaluation of this co-delivery vehicle Swiss Albino Mice were used. The ultrasonic atomization process led to the development of Dox-Ch-NP (50–150 nm), Pip-PLGA-NP (50–200 nm) and HAM (5 μm). The encapsulation efficiency was 32% and 67% in the case of Dox-Ch-NP and Pip-PLGA-NP, respectively. Sustained in vitro release of both drugs was achieved for 15 days. MTT-based cell cytotoxicity assay shows 88% cell viability in HEK-293 and 51% in HeLa cells after 24Hrs of treatment with HAM. The in-vivo study suggested 93% of tumor reduction with Dox-Ch-NP treatment, 75% reduction with Pip-PLGA-NP treatment While 100% reduction in tumor volume after 15 days of treatment completion. The in-vivo study also showed higher and faster tumor volume reduction in co-delivered drugs via HAM than in single drug-loaded nanoparticles. The results indicate the successful formulation of multi-drug hybrid carriers which can aid in generating an efficient anti-tumor therapeutic regimen for localized tumors with reduced chances of occurrence of multi-drug resistant tumors.