<p>Ocular anti-inflammatory activity of prednisolone acetate loaded chitosan-deoxycholate self-assembled nanoparticles</p>

Abstract

Background and purpose: Conventional topical ophthalmic aqueous solutions and suspensions are often associated with low bioavailability and high administration frequency, pulsatile dose and poor exposure to certain ocular parts. The aim of this study was to develop an ophthalmic nanoparticles loaded gel, for delivering prednisolone acetate (PA), to increase dosing accuracy, bioavailability, and accordingly, efficiency of PA in treating inflammatory ocular diseases. Methods: A novel formulation of self-assembled nanoparticles was prepared by the complexation of chitosan (CS) and, the counter-ion, sodium deoxycholate (SD), loaded with the poorly-water-soluble PA. Particle size, zeta potential, encapsulation efficiency (EE) and drug loading content (LC) of prepared nanoparticles were assessed. Moreover, the nanoparticles were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Drug release and eye anti-inflammatory potential of the prepared novel formulation was investigated. Results: Mean particle size of the nanoparticles have dropped from 976 nm ±43 (PDI 1.285) to 480 nm ±28 (PDI 1.396) when the ratio of CS-SD was decreased. The incorporation of 0.1-0.3% of polyvinyl alcohol (PVA), in the preparation stages, resulted in smaller nanoparticles: 462 nm ±19 (PDI 0.942) and 321 nm ±22 (PDI 0.454) respectively. DSC and FTIR results demonstrated the interaction between CS and SD, however, no interactions were detected between PA and CS or SD. Drug release of PA as received, in simulated tears fluid (pH 7.4), showed a twofold increase (reaching an average of 98.6% in 24 hours) when incorporated into an optimized nanoparticle gel formulation (1:5 CS-SD). Conclusion: The anti-inflammatory effect of PA nanoparticles loaded gel on female guinea pig eyes was significantly superior to that of the micronized drug loaded gel ( P < 0.05).

Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model

“…The high drug loading capacity is of prime importance for clinical applications to maximize the drug/excipients ratio and minimize the hazards associated with the use of unnecessary chemicals. Although data in Table 1 shows that the size of PEG2- b -PLA1 micelles (146.90 ± 4.29 nm) is larger than that of PEG2- b -PCL10 micelles (64.26 ± 0.55 nm), the former is still in the nanometer range and has the potential to enhance drug efficacy (Hanafy et al., 2019 ).…”

Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects

“…Some authors have used a different crosslinking agent, instead of TPP, such as sodium deoxycholate. For example, Hanafy et al [ 43 ] used a CH/PVA system crosslinked with sodium deoxycholate to embed prednisolone for the treatment of ocular inflammation diseases. Results obtained on female guinea pigs showed that optimized NPs formulation achieved a twofold increase in the prednisolone release after 24 h when compared with the commercial micronized drug loaded gel.…”

Chronic Inflammatory Diseases, Anti-Inflammatory Agents and Their Delivery Nanosystems

“…A new ophthalmic nanoparticulate gel composed of chitosan (CS), sodium deoxycholate (SD), and prednisolone acetate (PA) was prepared by Hanafy et al with the particle size of 480 nm ± 28 and the PDI of 1.396. In simulated tears of pH 7.4, the release of PA was found to be 98.6% in 24 h. The results of the anti-inflammatory in vivo test of the gel with NPs on guinea pig eyes was significantly better than the effect of the gel loaded with micronized PA [ 124 ].…”