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. 2020 Nov 1:162:1699-1710.
doi: 10.1016/j.ijbiomac.2020.07.306. Epub 2020 Aug 8.

Polypeptide and glycosaminoglycan polysaccharide as stabilizing polymers in nanocrystals for a safe ocular hypotensive effect

Marwa Donia  1 , Rihab Osman  2 , Gehanne A S Awad  2 , Nahed Mortada  2
Affiliations

Polypeptide and glycosaminoglycan polysaccharide as stabilizing polymers in nanocrystals for a safe ocular hypotensive effect

Marwa Donia et al. Int J Biol Macromol. .

Abstract

Improved ocular delivery of a poorly soluble anti-glaucoma drug, acetazolamide (ACZ), in a stable nanosuspension (NS) was the main target of the study. The anionic polypeptide, poly-γ-glutamic acid (PG) and the glycosaminoglycan, hyaluronic acid, were used to stabilize ACZ-NS prepared using the antisolvent precipitation (AS-PT) coupled with sonication technique. To endue in site biocompatibility with high tolerability, soya lecithin (SL) phospholipid has been also combined with polyvinyl alcohol (PVA). NS with uniform PS in the range 100-300 nm, high ζ > ±20 mV, and enhanced saturation solubility were produced. Targeting solvent removal with control on future particle growth, post-production processing of NS was done using spray drying. The carriers' composition and amount relative to ACZ-NS were optimized to allow for the production of a redispersible dry crystalline powder. Particles crystallinity was confirmed using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) in liquid and spray dried NS. The modified Draize test proved the safety and tolerability following application to rabbit eyes accompanying an efficient ocular hypotensive activity using a steroid glaucoma model.

Keywords: Acetazolamide; Antisolvent nanoprecipitation; Glaucoma; Low solubility; Spray drying.

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