Local drug delivery system using biodegradable polymers

Abstract

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs : gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), 1,25(OH) 2 vitamin D 3 , water insoluble small molecule drugs : fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug : nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period (1~3 days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

Preparation and characterization of chitosan–polylactide composites blended with Cloisite 30B for control release of the anticancer drug paclitaxel

“…Polylactide and its copolymers form a family of biodegradable and biocompatible polymers that have been widely used in biomedical applications. Among the various aliphatic degradable polyesters, polylactide (PLA) has been considered as one of the most interesting and promising biodegradable materials and has been used in medical applications, such as surgical sutures (Fambri, Pegoretti, Fenner, Incardona, & Migliaresi, 1997) drug delivery systems (Khang, Rhee, & Jeong, 2003) and bone fixtures (Bergsma, Bos, Rozema, Jong, & Boering, 1996). The use of these products in vivo has a tremendous advantage over traditional products due to the fact that PLA can be metabolized directly inside the body (Bergsma et al, 1995).…”

Synthesis and characterization of thermosensitive gelatin hydrogel microspheres in a microfluidic system

“…Due to the expected uniform and reproducible behaviors, controlling the size of the microspheres has important significance for controlled drug delivery system and cell delivery systems. 21,34,35 Therefore, the preparation of monodisperse hydrogel microspheres is needed. Recently, microfluidic systems that generate monodisperse droplets provide a promising alternative for the synthesis of monodisperse emulsions and microparticles.…”

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles

“…Poly(lactic-co-glycolic) acid (PLGA) is an excellent candidate, as it has been approved by FDA for human use because of its biodegradability and low systemic toxicity. [18][19][20] Its in vivo degradation takes several days allowing a prolonged release of the entrapped material, which results in fewer administrations and improved patient compliance. PLGA nanoparticles (PLGA NPs) could exhibit several advantages over direct systemic injection of TMAs, including 1) prolonged residence in circulation; 2) reduced immunogenicity; 21 and 3) combined extracellular and intracellular effect.…”