Current advances in research and clinical applications of PLGA-based nanotechnology

Abstract

Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases.

Figure 1. Poly(lactic-co-glycolic acid) chemical structure and nanoparticles

(A) Chemical structure of poly(lactic-coglycolic acid) (PLGA). (B) PLGA nanoparticles (NPs). PLGA NPs were produced by single emulsion process involving oil-in-water emulsification at 50:50 of lactic acid and glycolic acid. PLGA NPs were directly visualized under transmission electron microscope with negative staining.

Figure 2. Delivery of poly(lactic-co-glycolic acid) nanoparticles to a tissue engineered vascular graft (decellularized and heparin covalently linked porcine carotid artery graft)

Fluorescence molecule 6-coumarin was formulated into poly(lactic-co-glycolic acid) (PLGA) NPs, which were delivered into the graft through the lumen at pressure 50 and 200 mmHg for 10 min. The graft was sectioned in 7-μm tissue slides and the fluorescence signal from PLGA NPs was directly observed under fluorescence microscope. NP: Nanoparticle.

Figure 3. Poly(lactic-co-glycolic acid) nanoparticles deliver bFGF into the tissue engineered vascular graft and increase endothelial cell proliferation on the graft surface

Human recombinant bFGF or BSA was formulated in the poly(lactic-coglycolic acid) (PLGA) NPs, which were delivered to the decellularized and heparinized porcine carotid artery vascular graft. Empty PLGA NPs were served as a negative control. Human coronary artery endothelial cells were seeded on the graft luminal surface and cultured for 48 h. Living cells were stained with a florescence dye calcein-AM. The cells were observed and counted under fluorescence microscope. Magnification: ×200. bFGF: Basic FGF; BSA: Bovine serum albumin; NP: Nanoparticle.

Figure 4. Poly(lactic-co-glycolic acid) NPs deliver fluorescent molecule 6-coumarin and GFP gene (plasmid DNA) into the human coronary artery endothelial cells

6-coumarin or GFP containing plasmid DNA was formulated into the poly(lactic-co-glycolic acid) (PLGA) NPs, which were delivered to human coronary artery endothelial cells for 24 h. Florescence signal from PLGA NPs was directly observed under fluorescence microscope. GFP gene was successfully delivered into the cells and the gene expression was occurred. Magnification: ×400. GFP: Green-fluorescence protein; NP: Nanoparticle.