PLGA Microspheres with Alginate-Coated Large Pores for the Formulation of an Injectable Depot of Donepezil Hydrochloride

Abstract

As the main symptom of Alzheimer’s disease-related dementia is memory loss, patient compliance for donepezil hydrochloride (donepezil), administered as once-daily oral formulations, is poor. Thus, we aimed to design poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) with alginate-coated large pores as an injectable depot of donepezil exhibiting sustained release over 2–3 weeks. The PLGA MS with large pores could provide large space for loading drugs with high loading capacity, and thereby sufficient amounts of drugs were considered to be delivered with minimal use of PLGA MS being injected. However, initial burst release of donepezil from the porous PLGA MS was observed. To reduce this initial burst release, the surface pores were closed with calcium alginate coating using a spray-ionotropic gelation method. The final pore-closed PLGA MS showed in vitro sustained release for approximately 3 weeks, and the initial burst release was remarkably decreased by the calcium alginate coating. In the prediction of plasma drug concentration profiles using convolution method, the mean residence time of the pore-closed PLGA MS was 2.7-fold longer than that of the porous PLGA MS. Therefore, our results reveal that our pore-closed PLGA MS formulation is a promising candidate for the treatment of dementia with high patient compliance.

Development of L-Lysine-Loaded PLGA Microparticles as a Controlled Release System for Angiogenesis Enhancement

“…The average particle size was expressed as the volume mean diameter (D M ). The distribution width was described by the Span index, which was calculated using the following equation [ 39 , 41 ]: where D 90 , D 50 , and D 10 are the diameters for which 90%, 50%, and 10% of the particles were respectively below each value [ 39 ]. The test was repeated three times for each sample type.…”

Application of biodegradable microsphere injections: an anticancer perspective

“…Researchers have proposed that calcium alginate can significantly reduce the problem of initial burst release of PLGA microspheres. 65 In another study, Chen et al designed a hydrogel microsphere multifunctional drug delivery system (DDS) loaded with tetracycline hydrochloride and flamazine and using Fe 3 O 4 , hydroxyapatite, gelatin, chitosan, and hydrogel as carrier materials. In this injectable microsphere DDS, Fe 3 O 4 plays the role of magnetic targeting, hydroxyapatite is involved in bone conduction, gelatin provides better solubility, and chitosan and hydrogel provide gelatinization.…”

An Update on the Routes for the Delivery of Donepezil

“…Kim porous PLGA microspheres by adding ammonium bicarbonate and blocking the surface pores with calcium alginate coating by spray ionization gel method to avoid the explosive release of porous PLGA microspheres in the early stage. 48 In addition, Jakki et al prepared mango gum polymeric nanoparticles by emulsion cross-linking method, which proved that they have certain brain targeting. 49 As shown in Figure 2, Tao et al prepared cholesterol-modified pullulan nanoparticles through a self-assembly method to adsorb Polysorbate 80 on their surface, further enhancing the slow-release effect and leading to a good brain targeting function.…”

“…The results show that DP microspheres can be used for long-term treatment of AD. Kim et al prepared porous PLGA microspheres by adding ammonium bicarbonate and blocking the surface pores with calcium alginate coating by spray ionization gel method to avoid the explosive release of porous PLGA microspheres in the early stage …”