ABSTRACT
Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and 1H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p < .01) reduction (1.5-fold) of reactive oxygen species (ROS) accumulation was observed in lipopolysaccharides-stimulated RAW264.7 macrophages, revealing its potent antioxidant property. From the obtained results, it is concluded that folic acid functionalization of 5-FU-PNPs is an ideal approach for sustained and targeted drug delivery, thereby influencing better therapeutic effect.
Subject(s)
Chitosan/analogs & derivatives , Chitosan/chemistry , Fluorouracil/chemistry , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Polymers/chemistry , Animals , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems/methods , Fluorouracil/pharmacology , Folic Acid/chemistry , Humans , MCF-7 Cells , Mice , Particle Size , RAW 264.7 CellsABSTRACT
A vast amount of research on nanoparticles has been conducted in recent years with versatile applications in the field of drug delivery systems. Nanoparticles are designed as a carrier molecule to deliver drugs in a sustained and stimuli response manner. Recent advances in nanotechnology have led to the development of long circulating nanoparticles with high encapsulation efficiency. This article focuses on the properties such as biocompatibility and biodegradability, which are considered as essential criteria for nanoparticles to be successfully used as a carrier molecule in drug delivery systems. Physicochemical characterization of the nanoparticles such as size and size distribution, surface morphology, zeta potential and surface chemistry has a significant role in the successful formulation and applications in drug delivery systems. Mostly, the size and surface characteristics of nanoparticles enable enhanced intracellular accumulation in tumor cells through passive targeting mechanisms and rapid development of nanoengineering, and aid towards attaining active targeting delivery by co-functionalization of nanoparticles using appropriate targeting ligands. This article reviews the recent progress and development of employing different biocompatible and biodegradable nanoparticles in drug delivery systems. It also briefly recaps the important methods available to evaluate its biocompatibility, the mechanism of biodegradability and clearance properties of NPs.
ABSTRACT
In this study, green synthesis of gold nanoparticles (AuNPs) was achieved using the extract of eggplant as a reducing agent. Hyaluronic acid (HA) serves as a capping and targeting agent. Metformin (MET) was successfully loaded on HA capped AuNPs (H-AuNPs) and this formulation binds easily on the surface of the liver cancer cells. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, HR-TEM, particle size analyser and zeta potential measurement. Toxicity studies of H-AuNPs in zebra fish confirmed the in vivo safety of the AuNPs. The in vitro cytotoxicity results showed that the amount of MET-H-AuNPs enough to achieve 50% inhibition (IC50) was much lower than free MET. Flow cytometry analysis showed the significant reduction in G2/M phase after treatment with MET-H-AuNPs, and molecular level apoptosis were studied using western blotting. The novelty of this study is the successful synthesis of AuNPs with a higher MET loading and this formulation exhibited better targeted delivery as well as increased regression activity than free MET in HepG2 cells.
