Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

Abstract

Polymeric micelles of single and mixed poloxamines (Tetronic) were evaluated regarding their ability to host the antiglaucoma agent ethoxzolamide (ETOX) for topical ocular application. Three highly hydrophilic varieties of poloxamine (T908, T1107 and T1307) and a medium hydrophilic variety (T904), possessing a similar number of propylene oxide units but different contents in ethylene oxide, were chosen for the study. The critical micellar concentration and the cloud point of mixed micelles in 0.9 per cent NaCl were slightly greater than the values predicted from the additive rule, suggesting that the co-micellization is hindered. Micellar size ranged between 17 and 120 nm and it was not altered after the loading of ETOX (2.7-11.5 mg drug g -1 poloxamine). Drug solubilization ability ranked in the order: T904 (50-fold increase in the apparent solubility) . T1107 ffi T1307 . T908. Mixed micelles showed an intermediate capability to host ETOX but a greater physical stability, maintaining almost 100 per cent drug solubilized after 28 days. Furthermore, the different structural features of poloxamines and their combination in mixed micelles enabled the tuning of drug release profiles, sustaining the release in the 1-5 days range. These findings together with promising hen's egg test-chorioallantoic membrane biocompatibility tests make poloxamine micelles promising nanocarriers for carbonic anhydrase inhibitors in the treatment of glaucoma.

Glycine elicited self-assembly of amphiphilic star block copolymers with contradistinct hydrophobicities

“…This may be correlated to the hydrophilic character of T1307. The coexistence of unimers, micelles and loose clusters in very hydrophilic EO-PO copolymers agrees well with data in literature [85,88]. As a consequence, at 30°C there are only unimers and loose clusters coexisting by virtue of intermolecular interactions.…”

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

“…The kinetic stability of empty and hydrophobic drug-loaded micelles was assessed by measuring changes in particle size over time (Ribeiro et al, 2012). Briefly, samples were placed in air-tight containers at 25°C and analyzed for their particle size distribution on the day of the preparation (day 0) and at various time intervals over 30 days.…”

Polymeric micelles for oral drug administration enabling locoregional and systemic treatments

“…Combination of two or more copolymers having similar blocks of different length or dissimilar blocks can lead to mixed micelles if some requisites are fulfilled: the hydrophobic blocks have similar molecular weight and the copolymers exhibit different hydrophilic/hydrophobic balance [99][100][101]. Interest in mixed micelles relies on their improved thermodynamic and kinetic stability features compared to single copolymer micelles, which in turn favors drug encapsulation and prevents premature leakage.…”