Sustained Release of Brimonidine from a New Composite Drug Delivery System for Treatment of Glaucoma

Abstract

A novel layered double hydroxide (LDH) nanoparticle/thermogel composite drug delivery system (DDS) for sustained release of brimonidine (Bri) has been designed, prepared, and characterized in this study for treatment of severe glaucoma. Brimonidine is first loaded onto LDH (Bri@LDH) nanoparticles, which are then dispersed in the thermogel consisting of plenty of micelles based on poly(dl-lactic acid-co-coglycolic acid)-polyethylene glycol-poly(dl-lactic acid-co-coglycolic acid) (PLGA-PEG-PLGA) copolymer. The Bri@LDH/Thermogel DDS containing 125.0 μg/g of brimonidine has been found to sustainably release the drug for up to 144 h, significantly extending the drug release period compared to that from Bri@LDH nanoparticles. The Bri@LDH/Thermogel DDS is not cytotoxic to human corneal epithelial cells and shows good biocompatibility. In vivo drug release from the special contact lens made of Bri@LDH/Thermogel DDS has been sustained for at least 7 days, which more effectively modulates the relief of intraocular pressure (IOP). Thus, the Bri@LDH/Thermogel DDS is a promising drug delivery alternative that can be used for treatment of severe glaucoma.

A Recent Perspective on Noncovalently Formed Polymeric Hydrogels

“…Laponite in the gel is able to absorb host‐derived bioactive molecules and retain them for the formation of native ECM after degradation of PLGA‐PEG‐PLGA hydrogel. For specific application in the eye, an injectable therapeutic matrices based on triblock (PLGA‐PEG‐PLGA) was successfully tested in in vivo study for glaucoma treatment . In this study, the thermogel showed sustained‐delivery of at least 7 days, and could effectively modulate the relief of intra‐ocular pressure.…”

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

“…Layered double hydroxides (LDH) can be efficient ocular delivery vehicles for a series of active compounds, such as diclofenac sodium, phacolysin and brimonidine. [15][16][17] Based on the evidence that PepT-1 has been identified in the corneal epithelium of humans, we have recently reported an organic-inorganic intercalated nanocomposite of PRN loaded CTS-glutathione-valine-valine layered double hydroxides (CG-VV-PRN-LDH) for topical ocular drug delivery. 18 The multifunctional nanocomposites with target ligand of dipeptide VV have been demonstrated with active targeting of PepT-1 in animals and at the cellular level.…”

Mildly Cross-Linked Dendrimer Hydrogel Prepared via Aza-Michael Addition Reaction for Topical Brimonidine Delivery

“…3–5 Efforts have been devoted to develop drug delivery systems to extend drug activity, thus reducing dosing frequency and improving patient compliance. 6–8 Topical drug vehicles are expected to be biocompatible, mucoadhesive, and have suitable viscosity. 9, 10 Lipids, Hyaluronic acid, PEG, PLGA and chitosan are commonly used polymers as topical drug delivery carriers and have been fabricated into particles and hydrogels.…”

“…36, 37 The application of hydrogels can result in prolonged pre-corneal residence time and increased ocular bioavailability. 8, 38, 39 Our group has developed a hybrid dendrimer hydrogel/PLGA nanoparticles platform and used it to fabricate a brimonidine/timolol maleate combination formulation for topical application. 38 This platform is capable of enhancing drug bioavailability and substantially sustaining drug activity following topical administration.…”