PLGA Nanoparticle-Based Formulations to Cross the Blood–Brain Barrier for Drug Delivery: From R&D to cGMP

Abstract

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA formulations. Peptides and other linkers can be attached on the surface of PLGA to provide targeting delivery. With the newly published guidance from the FDA and the progress of current Good Manufacturing Practice (cGMP) technologies, manufacturing PLGA NP-based drug products can be achieved with higher efficiency, larger quantity, and better quality. The translation from bench to bed is feasible with proper research, concurrent development, quality control, and regulatory assurance.

In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin

“…Several strategies have been developed to improve the penetration of NPs into the brain. These strategies modify NPs with components that are designed to take advantage of BBB endocytosis pathways [65]. PLGA NP surfaces can be modified with positive charges, e.g., with chitosan, that electrostatically interact with negatively charged regions of the luminal surfaces, which help PLGA in crossing the BBB by adsorptionmediated transcytosis [66].…”

In Vitro Evaluation of Nasal Aerosol Depositions: An Insight for Direct Nose to Brain Drug Delivery

“…However, the presence of the blood–brain barrier (BBB), which protects the brain from the entry of toxic substances, is a crucial obstacle for therapeutics to access the CNS. Therefore, novel brain targeting DDS are required to overcome this barrier and to enhance drug potential to treat CNS diseases [ 2 , 3 ]. The advantages of pulmonary DDS over oral delivery, such as rapid absorption and onset, enhance drug transport across the BBB when formulated in suitable sized and lipophilic aerosolized particles [ 4 ].…”

PLGA-Based Nanoparticles for Neuroprotective Drug Delivery in Neurodegenerative Diseases

“…They need to be addressed for the successful development of such therapeutics [ 116 ]. However, new guidelines are established to facilitate the transposition from bench to clinic and ensure the product quality and safety [ 21 , 117 ].…”

“…These last years, a wide variety of preparation techniques for PLGA NPs were reported in the literature, i.e., single and double emulsion solvent evaporation, nanoprecipitation, coacervation and spray-drying [ 14 , 21 ]. The single and double emulsion solvent evaporation methods are the most frequently used: PLGA is dissolved into an organic phase emulsified with an aqueous medium containing surfactants or stabilizers prior to solvent evaporation and NP formation, corresponding to a single emulsion solvent evaporation method [ 22 ].…”