Biocompatible phospholipid-based mixed micelles for posaconazole ocular delivery: Development, characterization, and in - vitro antifungal activity

Abstract

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS.

In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia

“…Previously, we tried using EPC alone (100 mg) to encapsulate etomidate (10 mg), which resulted in large (average particle size > 140 nm) and unstable liposomes with fast drug release (drug release > 80% at 8 h under the same experimental conditions used in this study). Since hybrid drug delivery systems may make use of the advantages of different materials to obtain improved properties such as increased drug loading ability, more spherical shape and better homogeneity of the particles, desirable stability, and sustained drug release, other materials (e.g., Pluronic polymers, Tween 80, and chitosan) have been incorporated into EPC-based formulations [ 49 , 50 ]. In this study, it was hypothesized that the incorporation of lactoferrin together with Pluronic P123 in the EPC liposomes could achieve notably enhanced drug distribution in the brain and improved drug effects.…”

Recent development of polymer nanomicelles in the treatment of eye diseases

“…or nonionic surfactants (Pluronic ® F127, Pluronic ® F68, Tween80, Labrasol ® ALF, and d-a-tocopherol polyethylene glycol 1,000 succinate (TPGS)) were prepared to enhance the ophthalmic administration of the broad-spectrum antifungal medication, posaconazole (POS). Studies have shown that phospholipid-based mixed micelles significantly inhibit P-glycoprotein (P-gp)-mediated drug efflux (Osouli et al, 2023). The mean particle size of the polymer nanomicelles approximates 58 nm, demonstrating optimal stability for over a month, a gradual release pattern devoid of any noticeable initial burst, and an elevated level of in vitro antifungal activity.…”

Poloxamer 407 modified collagen/β-tricalcium phosphate scaffold for localized delivery of alendronate

“…13,14 Due to its favorable biocompatibility, biodegradability, and tolerability, P-407 has been employed in drug delivery systems. 15,16 However, its limited mechanical strength and rapid degradation in physiological environment have hindered its clinical application. 14,17 To address these limitations, researchers have incorporated various additives into P-407, such as viscosity modifiers, inorganic salt or crosslinking agent.…”