Formulation and Pathohistological Study of Mizolastine-Solid Lipid Nanoparticles-Loaded Ocular Hydrogels.

BACKGROUND: Mizolastine (MZL) is a dual-action nonsedating topical antihistamine anti-inflammatory agent that is used to relieve allergic conditions, such as rhinitis and conjunctivitis. Solid lipid nanoparticles (SLNs) are advanced delivery system in ophthalmology, with the merits of increasing the corneal drug absorption and hence improved bioavailability with the objective of ocular drug targeting. METHODS: First, MZL was formulated as MZL-SLNs by hot homogenization/ultrasonication adopting a 32 full factorial design. Solid-state characterization, in vitro release, and stability studies have been performed. Then, the optimized MZL-SLNs formula has been incorporated into ocular hydrogels using 1.5% w/v Na alginate and 5% w/v polyvinylpyrrolidone K90. The gels were evaluated via in vitro release as well as in vivo studies by applying allergic conjunctivitis congestion in a rabbit-eye model. RESULTS: The optimized formula (F4) was characterized by the highest entrapment efficiency (86.5±1.47%), the smallest mean particle size (202.3±13.59 nm), and reasonable zeta potential (-22.03±3.65 mV). Solid-state characterization of the encapsulation of MZL in SLNs was undertaken. In vitro results showed a sustained release profile from MZL-SLNs up to 30 hours with a non-Fickian Higuchi kinetic model. Stability studies confirmed immutability of freeze-dried MZL-SLNs (F4) upon storage for 6 months. Finally, hydrogel formulations containing MZL-SLNs, proved ocular congestion disappearance with completely repaired conjunctiva after 24 hours. Moreover, pretreatment with MZL-SLNs-loaded hydrogel imparted markedly decreased TNF-α and VEGF-expression levels in rabbits conjunctivae compared with post-treatment with the same formula. CONCLUSION: MZL-SLNs could be considered a promising stable sustained-release nanoparticulate system for preparing ocular hydrogel as effective antiallergy ocular delivery systems.

Ocular Inserts of Voriconazole-Loaded Proniosomal Gels: Formulation, Evaluation and Microbiological Studies.

BACKGROUND: Voriconazole (VRC) is a triazole broad spectrum antifungal drug, used in the management of versatile fungal infections, particularly fungal keratitis. The obligatory use of niosomal delivery of VRC may reduce the frequency of dosing intervals resulting from its short biological half time and consequently improve patient compliance. METHODS: VRC loaded proniosomes (VRC-PNs) were set by the coacervation technique and completely characterized. The developed formula was comprehensively assessed concerning in- vitro release behavior, kinetic investigation, and its conflict against refrigerated and room temperature conditions. A selected noisomal formula was incorporated into ocusert (VRC-PNs Ocu) formulated by 1% w/w hydroxypropyl methyl cellulose HPMC and 0.1% w/w carbopol 940. Eventually, in vitro antifungal activity against Candida albicans and Aspergillus nidulans was assessed by the cup diffusion method. RESULTS: The optimized VRC-PNs (Pluronic F127: cholesterol weight ratio 1:1 w/w) exhibited the highest entrapment efficiency (87.4±2.55%) with a spherical shape, proper size in nano range and a suitable Zeta potential of 209.7±8.13 nm and -33.5±1.85 mV, respectively. Assurance of drug encapsulation in nanovesicles was accomplished by several means such as attenuated total reflection Fourier-transform infrared spectroscopy, differential scanning calorimetry in addition to powder X-ray diffraction investigations. It displayed a biphasic in vitro release pattern and after 6 months of storage at a refrigerated temperature, the optimized formula preserved its stability. VRC-PNs Ocu proved a very highly significant antifungal activity matched with the free drug or nanosuspension which was extra assured by comparing its mean inhibition zone with that of 5% natamycin market eye drops. CONCLUSION: In conclusion, VRC-PNs Ocu could be considered as a promising stable sustained release topical ocular nanoparticulate system for the management of fungal infections.

The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration.

OBJECTIVE: The aim of this study is to develop, and characterize nanostructured lipid carriers (NLCs) of phenytoin (PHT) in order to improve its entrapment efficiency and sustained release to improve the healing process. METHODS: Twenty-seven patients with neuropathic diabetic foot ulceration (DFU) were enrolled in this study. Patients were comparable regarding size, grading of ulcer and control of diabetes with no major deformity. All patients were managed by weekly sharp debridement if indicated and offloaded with cast shoes. They were equally divided into three groups: PHT-NLC-hydrogel (0.5%w/v), phenytoin hydrogel (0.5%w/v) and blank hydrogel groups. Changes in wound area were monitored over 2 months. RESULTS: Baseline wound area of PHT-NLC, PHT and blank hydrogels were 5.50 ± 3.66, 3.94 ± 1.86 and 5.36 ± 2.14 cm2, respectively. Ulcers treated with PHT-NLC hydrogel showed smaller wound area compared to control groups (ρ < 0.05). The overall reduction in ulcer size were 95.82 ± 2.22% for PHT-NLC-hydrogel in comparison to 47.10 ± 4.23% and -34.91 ± 28.33% for PHT and blank-hydrogel (ρ < 0.001), respectively. CONCLUSION: PHT-NLC hydrogel speeds up the healing process of the DFU without adverse effects when compared to the positive and negative control hydrogels. Moreover, the study can open a window for topical application of NLCs loaded with PHT in the treatment of numerous dermatological disorders that resist conventional treatment. KEY MESSAGE: The delivery of drug molecules and their localization into the skin is the main purpose of the topical dosage forms. In this manuscript, the impact of topical phenytoin loaded nanostructured lipid carrier in improving wound healing in patients with neuropathic diabetic foot ulceration was investigated. Phenytoin loaded nanostructured lipid carrier dressing was found to be more effective than phenytoin hydrogel at the same concentration in healing of neuropathic diabetic foot ulcer.

Topical phenytoin nanostructured lipid carriers: design and development.

Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 23 factorial design. NLC formulations were characterized regarding their particle size (PS), zeta potential (ZP), entrapment efficiency percent (%EE), surface morphology, physicochemical stability, and in vitro release studies. The optimized NLC (F7) was further incorporated in 1%w/v carbopol gel and then characterized for appearance, pH, viscosity, stability, and in vitro drug release. The prepared NLCs were spherical in shape and possessed an average PS of 121.4-258.2 nm, ZP of (-15.4)-(-32.2) mV, and 55.24-88.80 %EE. Solid-state characterization revealed that the drug is dispersed in an amorphous state with hydrogen bond interaction between the drug and the NLC components. NLC formulations were found to be stable at 25 °C for six months. The stored F7-hydrogel showed insignificant changes in viscosity and drug content (p>.05) up to six months at 25 °C that pave a way for industrial fabrication of efficient PHT products. In vitro release studies showed a sustained release from NLC up to 48 h at pH 7.4 following non-Fickian Higuchi kinetics model. These promising findings encourage the potential use of phenytoin loaded lipid nanoparticles for future topical application.

Nanoemulsifying drug delivery system to improve the bioavailability of piroxicam.

OBJECTIVE: The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy. MATERIALS AND METHODS: The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets. RESULTS AND DISCUSSION: The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (Feldene®) (commercial dosage form (CD)). The relative bioavailability of S-sSNEDDS (F12) relative to PP or CD was about 151.01 and 98.96%, respectively. CONCLUSION: The obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.