Effervescent based nano-gas carrier enhanced the bioavailability of poorly aqueous soluble drug: A comprehensive mechanistic understanding

Abstract

The low aqueous solubility of drug molecules is a considerable hurdle to produce the desired pharmacological effect through any biological route of drug administration. Hence, most of the chemotherapeutic drugs exhibit low bioavailability as well as non-specific toxic effects on the human body. Luteolin (LUT), one of the richest flavonoids, is proven to be a cancer preventive agent for numerous human cancer cell lines. The hydrophobicity of LUT, on the other hand, is a major concern for it's low oral bioavailability. On this account, we have utilized a versatile strategy to engineer a novel effervescent based self-assemble nano-gas drug carrier (NG) for poorly water-soluble compounds, which is hypothesized to be a self-emulsifying agent for drug molecules in the intestinal aqueous environment to form nanoemulsion and eventually escalate the efficacy. The size of the optimized nanoformulation after characterization was found to be 450 ± 100 nm with a negative surface charge (zeta potential value of −27.8 mV). Additionally, SAXS analysis verified the conversion of the carrier into nano-micelles. In vitro studies show NG has a lot of potential for improving LUT's solubility and as a result, LUT can show a significant effect (approximately 2-fold) on pancreatic cancer cell lines at minimal concentration. The permeability enhancement effect of our excipients also showed an additional advantage for the utilization of this concept in the oral formulation development of drug compounds.