Niosomes: Do They Increase the Potency of Topical Natamycin Ketorolac Formula in Treating Aspergillus Keratitis? An Experimental Study.

Purpose: Formulation of new drug delivery system as Natamycin (NT)-loaded nanoparticle niosomal formulae mixed in different polymer gel, with the addition of ketorolac tromethamine (KETR). Pharmaceutical and experimental assessments to evaluate their safety and efficacy in treating Aspergillus keratitis. Methods: NT nanoparticle niosomes prepared by reverse-phase evaporation technique were mixed in different polymers, with the addition of KETR. Two formulae are evaluated in this study: F1 [NT-loaded nanoparticle niosomes/0.5% KETR 4% carboxymethyl cellulose (Na.CMC) gel], F2 [NT-loaded nanoparticle niosomes/0.5% KETR 2% hydroxypropylmethyl cellulose (HPMC)-E4 gel], and mixed marketed products (MMP), namely Natamet® and Ketoroline® suspension eye drops. NT-loaded nanoparticle niosomes/0.5% KETR were evaluated through viscosity determination, mucoadhesive attractive force, and in vitro NT release studies. The in vivo antifungal evaluation was performed on 45 albino rabbits, Aspergillus species were inoculated in right corneas of all rabbits, and then rabbits were subdivided into 3 groups, 15 rabbits each: Group A: received F1, Group B: received F2, and Group C: received MMP. Daily examination of rabbits was performed for evaluation of corneal infiltration, and signs of iritis. Two weeks later, rabbits were euthanized; their corneas were dissected at the limbus and sent for histopathological evaluation. Results: F1 had a higher viscosity and more mucoadhesive power than F2, and showed better results on corneal infiltration, and level of hypopyon. These results were consistent with the histopathological examination. Conclusion: The formula of NT-loaded nanoparticle niosomes/0.5% KT 4% Na.CMC gel has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application.

Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies.

OBJECTIVES: This study was aimed to develop dual-purpose natamycin (NAT)-loaded niosomes in ketorolac tromethamine (KT) gels topical ocular drug delivery system to improve the clinical efficacy of natamycin through enhancing its penetration through corneal tissue and reducing inflammation associated with Fungal keratitis (FK). SIGNIFICANCE: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers. METHODS: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits. RESULTS: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75 ± 0.64 to 498.95 ± 0.64 nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96-77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN®) and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN® and Ketoroline®). CONCLUSIONS: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues.

Transdermal drug delivery of paroxetine through lipid-vesicular formulation to augment its bioavailability.

Paroxetine (PAX) is the most potent serotonin reuptake blocker antidepressant clinically available. This study is aimed to reduce the side effects accompanied with the initial high plasma concentration after oral administration of PAX and fluctuations in plasma levels and also to decrease the broad metabolism of the drug in the liver by developing and optimizing liposomal transdermal formulation of PAX in order to improve its bioavailability. PAX liposomes were prepared by reverse phase evaporation technique using lecithin phosphatidylcholine (LPC), cholesterol (CHOL) and drug in different molar ratios. The prepared liposomes were characterized for size, shape, entrapment efficiency and in vitro drug release. The studies demonstrated successful preparation of PAX liposomes. The effect of using different molar ratios of (LPC:CHOL) on entrapment efficiency and on drug release was studied. Liposomes showed percentage entrapment efficiency (%EE) of 81.22 ± 3.08% for optimized formula (F5) which composed of (LPC:CHOL, 7:7) and 20mg of PAX, with average vesicle size of 220.53 ± 0.757 nm. The selected formula F5 (7:7) was incorporated in gel bases of HPMC-E4M (2%, 4%, and 6%). The selected formula of PAX liposomal gel of HPMC-E4M (2% and 4%) were fabricated in the reservoir type of transdermal patches and evaluated through in vitro release. After that the selected formula of PAX liposomal gel transdermal patch was applied to rabbits for in vivo bioavailability study in comparison with oral administration of the marketed PAX tablet. An HPLC method was developed for the determination of PAX in plasma of rabbits after transdermal patch application and oral administration of the marketed PAX tablets of 20mg dose. The intra- and inter-day accuracy and precision were determined as relative error and relative standard deviation, respectively. The linearity was assessed in the range of 5-200 ng/ml. Pharmacokinetic parameters were determined as the C(max) of PAX liposomal transdermal patch was found to be 92.53 ng/ml at t(max) of 12h and AUC(0-48) was 2305.656 ngh/ml and AUC(0-∞) was 3852.726 ngh/ml, compared to the C(max) of 172.35 ng/ml after oral administration of the marketed PAX tablet with t(max) of 6h and AUC(0-24) was 1206.63 ngh/ml and AUC(0-∞) was 1322.878 ngh/ml. These results indicate improvement of bioavailability of the PAX after liposomal transdermal patch application and sustaining of the therapeutic effects compared to oral administration.