Modulating surface charge of dexamethasone non-spherical microcrystals for improved inner ear delivery.

It is important to achieve precise surface charge manipulation of non-spherical drug microcrystals using facile and time-efficient methods for local drug delivery. In this study, silk-coated dexamethasone (DEX) non-spherical microcrystals were synthesized by precipitation technique followed by alternate deposition of poly(allylamine hydrochloride) (PAH) (or PAH-coated Fe3O4) and silk fibroin (SF) via layer-by-layer assembly. EDC and glutaraldehyde were employed to manipulate positive or negative charge of particles by simple chemical cross-linking reactions, respectively. In vivo assessment was carried out by intratympanic (IT) injection of DEX non-spherical microcrystals in guinea pigs. In vivo pharmacokinetic results demonstrate that negatively charged DEX microcrystals appeared to improve outcomes of inner ear delivery in comparison to positively-charged counterparts. This is partly because of the adhesive features of the SF. The present study may provide new ideas to construct surface charge-tunable drug delivery vehicles that are capable of crossing biological barriers, especially for inner ear delivery due to the simple and practical strategy.

Polymeric non-spherical coarse microparticles fabricated by double emulsion-solvent evaporation for simvastatin delivery.

Polymeric particles with non-spherical shape or coarse surface have distinct advantages for drug delivery, tissue regeneration and immunomodulation respectively, but it is not easy to control polymeric microparticles in required geometry and surface texture simultaneously. In this study, polymeric non-spherical microparticles with coarse surface were successfully prepared by double emulsion-solvent evaporation technique in the presence of ammonium bicarbonate and the formation mechanism was proposed. In addition, simvastatin was encapsulated in poly[lactic-co-(glycolic acid)] (PLGA) non-spherical microparticles with coarse surface by the same technique and the release kinetics in vitro was fitted as well, which not only enrich the encapsulation techniques of liposoluble drugs in polymeric non-spherical carriers but also envision the potential application for alveolar ridge preservation with local delivery of simvastatin.

Carboxymethyl Cellulose-Coated Tacrolimus Nonspherical Microcrystals for Improved Therapeutic Efficacy of Dry Eye.

Dry eye (DE) is a highly prevalent ocular surface disease which affects the quality of life and results in low working efficiency. Frequent instillation is required due to low bioavailability of conventional eye drops. The aim of this study is to develop a novel formulation of tacrolimus (TAC), routinely prescribed for DE, by combination of the microcrystal technology and layer-by-layer assembly. First, nonspherical tacrolimus microcrystals (TAC MCs) are synthesized by antisolvent-induced precipitation. These TAC MCs are modified by alternate deposition of poly(allylamine hydrochloride) (PAH) and carboxymethyl cellulose (CMC) subsequently to obtain CMC-coated TAC MCs (TAC-(PAH/CMC)3 ). The resultant formulations are evaluated in vivo in a mouse DE model induced by an intelligently controlled environmental system. Compared with commercially available TAC eye drops and the TAC MCs counterpart, TAC-(PAH/CMC)3 exhibits superior therapeutic performance with reduced drug instillation frequency, which is attributed to the nonspherical geometry of MCs, the lubricant, mucoadhesive effect of CMC, and the anti-inflammatory function of TAC. Therefore, TAC-(PAH/CMC)3 represents a better option for the management of DE.

Silk-coated dexamethasone non-spherical microcrystals for local drug delivery to inner ear.

The local drug delivery systems play an important role in treating sudden sensorineural hearing loss. In this work, we synthesized dexamethasone microcrystals (DEX MCs) using precipitation technique followed by silk coating via layer-by-layer assembly. Compared to raw DEX, the physicochemical properties including shape, crystal form, dispersity, dissolution or sustained release, of DEX MCs or poly-l-lysine/silk fibroin (PLL/SF) multilayers-coated DEX MCs (DEX-(PLL/SF)3) were investigated. More importantly, after a single intratympanic administration in guinea pigs, DEX-(PLL/SF)3 was uniformly distributed on the round window membrane (RWM) in comparison with raw DEX and DEX MCs. And increased concentration of DEX treatment resulted in higher perilymph DEX levels. No significant morphological change and inflammatory responses on the cochlear tissue were observed. Thus, the DEX-(PLL/SF)3 formulation could be a novel local drug delivery strategy to realize safe, efficient and sustainable DEX delivery into inner ear across RWM.