Controlled and Extended Release of a Model Protein from a Microsphere-Hydrogel Drug Delivery System

Abstract

In extended ocular drug delivery applications, it is necessary to exert control over the release characteristics of the drug. Design considerations must be made to limit the initial burst (IB) and ensure complete release of drug from the drug delivery system (DDS). In this study, ovalbumin was used as a model protein to explore the effects on release of polymer formulation and fabrication technique in poly(lactic-co-glycolic acid) (PLGA) microspheres. Furthermore, the effect on release of suspending these microspheres in an injectable, thermo-responsive poly(N-isopropylacrylamide)-based hydrogel was determined. To characterize release, ovalbumin was radiolabeled with iodine-125. Regardless of polymer formulation or fabrication technique, pulsatile release was achieved with a second burst occurring after ~70 days for microspheres alone. Suspending PLGA 75:25 microspheres within hydrogel reduced the IB by ~75%, delayed the second burst by 28 days, and extended release out to ~200 days with steadier, consistent release throughout compared to microspheres alone. The combined microsphere-hydrogel DDS remains injectable through small-gauge needles and may have many applications, namely ocular drug delivery to the posterior segment.

A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride

“…In recent years, various ophthalmic drug-delivery systems have been developed for ocular carriers, including liposomes (LPs), [6][7][8] nanoparticles, 9,10 microspheres, 11,12 nanostructured lipid carriers, 13,14 in situ gels, 15,16 and contact lenses. 17 Among these, LPs have proved to be a promising formulation for ocular drug transport in the last decade, because they include enclosed vesicles and bilayer structures.…”

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model

“…18,21,22 In addition, sustained release of drugs with tailored characteristics can be achieved by encapsulating drugs within PLGA microspheres. 17 Moreover, our previous studies have demonstrated controlled release of bioactive anti-VEGF therapeutics from PLGA microspheres for approximately 200 days. 17,20 To further investigate the potential clinical usage of anti-VEGF-loaded DDS, in vivo studies of the safety and biocompatibility of the device is required, preferentially in the eyes of an animal model that has similar eye size and retinal structure as a human.…”

“…15,16 Therefore we developed a DDS consisting of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres suspended within a thermo-responsive, injectable hydrogel to address this clinical requirement. 17,18 Thermo-responsive hydrogel has demonstrated great promise in drug delivery owing to their ability to change physical state rapidly and is reversible. Below the transition temperature (∼32°C) the hydrogel is swollen in liquid-like form, and above the transition temperature the hydrogel collapses to solidified form.…”

Increasing Distribution of Drugs Released from In Situ Forming PLGA Implants Using Therapeutic Ultrasound

“…They are particularly important in cancer therapy where the therapeutic index of the drug is often quite small and the stability of biologic agents is limited. 24, 40 In situ forming implants (ISFI) used for local drug delivery directly into the tissue of interest (e.g. a tumor) are an attractive alternative route to oral and intravenous administration.…”