(176aq) Porous and Degradable HA Particles As Sustainable Multiple Drug Releasing Capabilities

Hyaluronic acid (HA) is a natural, non-toxic biopolymer produced in vertebra tissues and microorganisms’ membrane. HA is an excellent biopolymer and exists in many parts of human bodily fluids and tissues including synovial fluids, the vitreous humor of the eye and cartilages. As the main component of extracellular matrix, HA is composed of N-acetyl glucosamine and glucuronic acid repeating units are a glycosaminoglycan (GAG) family. The inherent biological functions such as inhibition of tumor growth, prevention of metastases for the cancer cells, promoting gene expression, and improving the wound healings and so on make HA as excellent material in biomedical applications. Consequently, HA based materials are soft, biodegradable, biocompatible, viscoelastic and non-immunogenic in addition to high moisture holding and/or hydration capability allowing them to be used in cosmetics and biotechnological industries as tissue filler materials, moisturizing and skin care products, healing of the arthritis and joints as lubricants and wound dressing materials and particularly drug delivery vehicles (DDV).

In this study, HA particles are formed by use of crosslinker such as divinylsulfone (DVS) and trisodium trimetaphosphate (STMP) to obtained porous and degradable HA microparticles to be employed as DDV. The size, morphological and physicochemical characterization of the HA particles were carried out by optic microscope, Dynamic Light Scattering (DLS) scanning electron microscope (SEM), thermogravimetric analysis (TGA), FT-IR spectroscopy, and zeta potential measurements. Additionally, surface area, pore size and pore volume of these HA particles were measured by N₂ adsorption analysis. The hydrolytic degradation of HA particles at physiological pH conditions, 7.4 and 37.5 °C were also investigated. Various types of drugs including corticosteroid, antibiotic, or chemotherapy drugs were loaded physically and chemically into HA particles. Furthermore, combination of these drug loading and release studies were performed in porous and degradable HA particle for sustained drug delivery application. For example, HA particles were conjugated with dexamethasone as a corticosteroid drug by using 1,1’-carbonyldiimidazole (CDI) coupling agent via esterification reaction and this dexamethasone loaded HA particles were further conjugated with ciprofloxacin, antibiotic drug. Moreover, 5-fluorouracil (5-FU), cisplatin, and doxorubicin as cancer drugs were also loaded into HA particles by encapsulation method during HA particle preparation. The in vitro multiple drug release profile from these drugs loaded HA particles were investigated at physiological conditions e.g., pH 7.4 and 37.5 °C to determine the sustainable and long-term drug release capabilities of these HA based particles.