Glycyrrhetinic acid conjugated zein capped aminated mesoporous silica nanoparticle-based dual drug delivery system for liver: A pH-dependent triggered release

Abstract

Nano-scale drug delivery systems have captivated the scientific community due to their controlled and targeted drug release. Nano carrier-based combination chemotherapy has improved pharmacokinetics of drugs compared to single drug administration. The objective of the present work is to develop a drug delivery system based on aminated mesoporous silica nanoparticles (AMSN) and zein, a plant protein for the co-delivery of 5-Fluorouracil (5-FU) and curcumin (CUR). The AMSN was obtained by the co-condensation method, which can accommodate CUR in its pores. Then the silica core was coated with glycyrrhetinic acid conjugated zein nanoparticle, which could act as a pH-responsive gatekeeper for AMSN as well as a carrier for 5-FU. The structure of the hybrid nanoparticle was characterized by FT-IR, XRD, SEM, TEM, DLS and TG analyses. The release studies were carried out at pH 7.4 and 5.5. The greater extent of drug release occurred at pH 5.5. About 78.00% of drug release happened within 120 h for 5-FU and 71.30% within 120 h for CUR. The in vitro release of drugs was analyzed using Peppas's empirical equation to understand the release mechanism. In vitro cell viability studies were conducted using MTT assay on HepG2 liver cancer cells and 3T3-L1 normal cells. At 1000 μg/mL, the drug carrier shows greater than 90.00% cell viability and AMSN-CUR/Z-GA-5-FU showed a higher toxicity of 68.80%. The results demonstrate that the prepared material is an efficient DDS for anticancer activity.