Amphiphilic Acrylic Nanoparticles Containing the Poloxamer Star Bayfit® 10WF15 as Ophthalmic Drug Carriers

Abstract

Topical application of drops containing ocular drugs is the preferred non-invasive route to treat diseases that affect the anterior segment of the eye. However, the formulation of eye drops is a major challenge for pharmacists since the access of drugs to ocular tissues is restricted by several barriers. Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the treatment of ocular hypertension in glaucoma. However, large ACZ doses are needed which results in systemic side effects. Recently, we synthesized copolymers based on 2-hydroxyethyl methacrylate (HEMA) and a functionalized three-arm poloxamer star (Bayfit-MA). The new material (HEMA/Bayfit-MA) was engineered to be transformed into nanoparticles without the use of surfactants, which represents a significant step forward in developing new ophthalmic drug delivery platforms. Acetazolamide-loaded nanocarriers (ACZ-NPs) were prepared via dialysis (224 ± 19 nm, −17.2 ± 0.4 mV). The in vitro release rate of ACZ was constant over 24 h (cumulative delivery of ACZ: 83.3 ± 8.4%). Following standard specifications, ACZ-NPs were not cytotoxic in vitro in cornea, conjunctiva, and macrophages. In normotensive rabbits, ACZ-NPs generated a significant intraocular pressure reduction compared to a conventional solution of ACZ (16.4% versus 9.6%) with the same dose of the hypotensive drug (20 µg). In comparison to previously reported studies, this formulation reduced intraocular pressure with a lower dose of ACZ. In summary, HEMA:Bayfit-MA nanoparticles may be a promising system for ocular topical treatments, showing an enhanced ocular bioavailability of ACZ after a single instillation on the ocular surface.

Non-Ionic Surfactants for Stabilization of Polymeric Nanoparticles for Biomedical Uses

“…To introduce ethoxy silane end-capping group, (3-isocyanatopropyl) triethoxysilane can be utilized to react with the hydroxyl groups of poloxamers under the catalysis of 2-ethyl-hexanoate. For the coupling of methacrylate/acrylate, methacryloyl chloride/acryloyl chloride reacts with hydroxyl groups on both ends, resulting in higher mechanical properties [241,242]. In this context, in 2021, Popescu et al developed a hydrogel from a natural polymer and poloxamer 407 obtained by thiol-acrylate photopolymerization to be employed as a wound dressing [243].…”

Particle and Gel Characterization of Irinotecan-Loaded Double-Reverse Thermosensitive Hydrogel

“…Irinotecan is a water-soluble camptothecin derivative for the chemotherapy of metastatic cancer of colon and rectum [ 9 ]. It was reported that this drug has been used intravenously [ 10 , 11 , 12 ] and orally [ 13 , 14 ]; however, their cytotoxicity and gastrointestinal toxicity were the major clinical problems related with irinotecan, an anti-tumour drug in human subjects, resulted in its limited use [ 15 , 16 , 17 ]. Hence, to solve these problems, other alternatives should be developed.…”

Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents

“…Twenty-four-well plates and cells at a 2 × 10 4 cells/well concentration were seeded for the in vitro tolerance study. The MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (Sigma Aldrich) cytotoxicity assay was used [15,60]. MTT technique is widely employed for assessing toxicity in novel developed systems [14,15].…”

“…The MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (Sigma Aldrich) cytotoxicity assay was used [15,60]. MTT technique is widely employed for assessing toxicity in novel developed systems [14,15]. Cells were exposed to gelatin (30 mg/mL), GNP (10 mg/mL and 30 mg/mL) and TM-GNP (10 mg/mL, 20 mg/mL and 30 mg/mL) at different exposure times (1 h, 4 h and 24 h).…”

“…The development of new formulations enhancing drug permeation, bioavailability and safety profile after ocular instillation has become one of the most important challenges in pharmaceutical technology in recent years [14][15][16]. Several novel drug delivery systems have been developed like nanoparticles, microparticles, microemulsions, hydrogels or contact lenses among others, to achieve more effective therapies [17][18][19][20][21].…”