Injectable controlled release depots for large molecules

Abstract

Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.

Water-based preparation of spider silk films as drug delivery matrices

“…According with the mentioned work, silk is an important alternative to PLGA and the advantage of using silk materials consists in the fact that silk will degrade slower than PLGA. Moreover, in general the degradation of a DDS could lead to toxic residuals and affect the local area where it is implanted, such as change the local pH or even stimulate an undesired immune response [39][40][41]. One of the great advantages of using eADF4(C16) proteins in developing depot systems, is the biodegradability of this protein material.…”

Biodegradable Magnetic Silica@Iron Oxide Nanovectors with Ultra-Large Mesopores for High Protein Loading, Magnetothermal Release, and Delivery

“…[1][2][3][4][5][6][7][8][9][10][11] The absence of particle biodegradability prevents almost always the approval of the food and drug administration (FDA) and other regulatory agencies to enter the pharmaceutical market. Non-degradable nanomaterials are indeed raising concerns of toxicity due to their uncontrolled bio-accumulation.…”

Does PLGA microparticle swelling control drug release? New insight based on single particle swelling studies

“…Poly(lactic-co-glycolic acid) (PLGA)-based microparticles offer a great potential as parenteral controlled drug delivery systems and are continuously increasing in practical importance [1]. Several products based on PLGA microparticles are available on the market, such as Zoladex, Risperdal Consta, Gonapeptyl, and Decapeptyl (used for the treatment of cancer or disorders of the central nervous system).…”