PLGA Nanoparticle-Based Formulations to Cross the Blood–Brain Barrier for Drug Delivery: From R&D to cGMP
Kaining Zhi,
Babatunde Raji,
Anantha R. Nookala,
Mohammad Moshahid Khan,
Xuyen H. Nguyen,
Swarna Sakshi,
Tayebeh Pourmotabbed,
Murali M. Yallapu,
Harry Kochat,
Erene Tadrous,
Shelby Pernell,
Santosh Kumar
Affiliations
Kaining Zhi
Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA
Babatunde Raji
Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA
Anantha R. Nookala
Covance Inc., Kinsman Blvd, Madison, WI 53704, USA
Mohammad Moshahid Khan
Department of Neurology, College of Medicine, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN 38163, USA
Xuyen H. Nguyen
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA
Swarna Sakshi
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA
Tayebeh Pourmotabbed
Department of Microbiology, Immunology and Biochemistry, College of Medicine, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA
Murali M. Yallapu
Department of Immunology and Microbiology, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
Harry Kochat
Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA
Erene Tadrous
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA
Shelby Pernell
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA
Santosh Kumar
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA
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.
