Abdallah, M., D. I. Nesseem, and A. A. Abdelbary, "TOPICAL DELIVERY OF QUERCETIN LOADED TRANSFERSOMES FOR WOUND TREATMENT: IN VITRO AND IN VIVO EVALUATION", International Journal of Applied Pharmaceutics, vol. 13, issue 5, pp. 189-197, 2021.
El-Dahmya, R. M., A. H. Elshafeey, N. A. A. E. Gawad, and I. Elsayed, "Statistical optimization of nanostructured gels for enhancement of vinpocetine transnasal and transdermal permeation", Journal of Drug Delivery Science and Technology, vol. 66, pp. 102871, 2021.
Latif, R., R. R. Makar, E. A. Hosni, and O. N. Elgazayerly, "The potential of intranasal delivery of nanocrystals in powder form on the improvement of zaleplon performance: assessment.", Drug development and industrial pharmacy, vol. 47, issue 2, pp. 268-279, 2021. Abstract

OBJECTIVE: The present work focuses on improving zaleplon (ZAP) performance through nanosizing its insoluble particles which were then delivered intranasally in powder form.

SIGNIFICANCE: Since nanopowders have an exceptional ability to cross cell membrane, their absorption is facilitated in the solid form. Hence, delivering insoluble ZAP nanocrystals (NC) through intranasal route improves its bioavailability due to both nanosization and the escape of hepatic metabolism.

METHODS: Nanocrystals were prepared by anti-solvent precipitation followed by probe sonication in presence of Soluplus, Poloxamer-188 (0.25%), sodium lauryl sulfate (0.5%), and mannitol. Physicochemical evaluation of the prepared NC was done by DSC and XRPD. TGA was performed for stability detection. permeation study through isolated cattle nasal mucosal membrane, in addition to an bioavailability study was performed for assessment of the prepared NC.

RESULTS: Nanosization to 200 nm contributed to the enhancement in dissolution ∼100% within 30 min and reduced half-life to 1.63 min. Confirmation of adsorption of polymers over NC' surface was elucidated. TGA confirmed their thermal stability. permeation study showed a 2.7 enhancement ratio in favor of the prepared NC. Both the extent and rate of NC absorption through nasal mucosa of rabbits were significantly higher ( ˂ .05) than in case of oral tablets. The relative bioavailability of NC was increased 3.14 times as compared to the Sleep aid tablets.

CONCLUSION: The intranasal delivery of nanoscale ZAP powder proved to be a successful alternative to oral formulations that suffer poor absorption and limited bioavailability.

El Komy, M. H., and A. A. Abdelrahman, "The Influence of Solid/Solvent Interfacial Interactions on Physicochemical and Mechanical Properties of Ofloxacin", Journal of Pharmaceutical Innovation volume, vol. 16, pp. 160-170, 2021.
Khalil, R. M., S. K. El Arini, M. M. AbouSamra, H. S. Zaki, O. N. El-Gazaerly, and A. A. Elbary, "Development of Lecithin/Chitosan Nanoparticles for Promoting Topical Delivery of Propranolol Hydrochloride: Design, Optimization and In-Vivo Evaluation.", Journal of pharmaceutical sciences, vol. 110, issue 3, pp. 1337-1348, 2021. Abstract

Propranolol (PPL) administered orally is considered as the first line drug for the treatment of infantile hemangioma, however several systemic adverse effects limit its use. For this reason, our work tackles the development and evaluation of PPL loaded chitosan nanoparticles (NPs), as an effective alternative for the treatment of infantile hemangioma. PPL -NPs were prepared using the double emulsion technique and the influence of the formulation variables on drug entrapment efficiency (EE), particle size (PS), percent released after 24 h (%R) and zeta potential (ZP) were optimized using full factorial design. Two systems, namely F3 and F28 showing highest E.E., ZP and %R with lowest PS, were fully characterized for DSC and TEM and incorporated into hydrogel with adequate viscosity. After ensuring safety for the selected nanoparticle, the hydrogel containing the optimized system was applied topically to rats. The in-vivo skin deposition in rats showed an accumulation of propranolol from the lecithin/chitosan nanocarrier by 1.56-1.91-fold when compared to the drug solution. The obtained result was further supported by the confocal laser scanning microscopy which showed fluorescence across the skin. PPL-HCL-loaded lecithin/chitosan nanoparticles could be considered as a potential candidate for treating infantile hemangiomas (IH) by maintaining therapeutic concentration topically while minimizing systemic side effects.

El-Said, I. A., A. A. Aboelwafa, and O. N. Elgazayerly, "Optimization of taste-masked dapoxetine oral thin films using factorial design: and evaluation.", Pharmaceutical development and technology, vol. 26, issue 5, pp. 522-538, 2021. Abstract

Dapoxetine HCl is used for the treatment of premature ejaculation. Dapoxetine is primarily metabolized in the liver and kidney and its metabolites are inactive; resulting in reduced bioavailability. Also, one of the commonly encountered issues in the oral dapoxetine formulae is its bitter taste. Thus, the objective of this study was to develop and to optimize novel dapoxetine taste-masked oral thin films (OTFs), to offer a faster dissolution rate, rapid release pattern, lower liver metabolism, and better patient compliance. To achieve our goal, the applicability of either pullulan or maltodextrin as strip forming polymers were investigated in the preparation of (OTFs), while glycerol was used as a plasticizer. Also, the physicochemical characteristics of dapoxetine in a resinate complex with AmberLite -IRP69 as taste masking were evaluated. Furthermore, a 2 factorial design was used to study and to optimize the effect of the independent variables (strip forming polymer (X), glycerol (X) and AmberLite (X) amounts) on the disintegration time (Y), degree of elongation (Y), and degree of drug release in phosphate buffer pH 6.8 at 5 minutes (Q5min, Y) as responses. P2 batch (OTF) (pullulan 96 mg, glycerol 12 mg, AmberLite 32 mg, and dapoxetine 30 mg) was identified as an optimized formulation showing an disintegration time 9.33 s, 35.56% elongation, and 91.43% Q5min; excellent disintegration time; good overall taste acceptability and stable resinate complex.

Shalaby, R. A., O. El-Gazayerly, and M. AbdAllah, "Cubosomal Betamethasone-Salicylic Acid Nano Drug Delivery System for Enhanced Management of Scalp Psoriasis.", International journal of nanomedicine, vol. 17, pp. 1659-1677, 2022. Abstract

Introduction: Betamethasone dipropionate (BD), a potent corticosteroid, and salicylic acid (SA), a keratolytic agent, have been used in combination to treat scalp psoriasis; however, undesirable side effects associated with their prolonged topical use are inevitable. In this study, BD and SA were loaded into cubosomes, a nanoparticulate system with outstanding biocompatibility, bio-adhesivity and penetration power.

Methods: Design of experiments (DOE) was utilized to prepare thirteen different cubosomal dispersions by emulsification technique using glycerol monoolein (GMO) as a lipid phase and Poloxamer 407 (P407) as a surfactant, sodium carboxymethyl cellulose (SCMC) was added to enhance the dispersions' rheological properties. The thirteen dispersions were in-vitro characterized for their particle size, polydispersity index (PDI), zeta potential, BD and SA content and rheological behaviour. The desirability of an optimized formula (OF) was set to the smallest particle size, lowest zeta-potential and highest viscosity. The OF was in-vitro characterized for the same parameters in addition to transmission electron microscope imaging and in-vitro drug release. The OF's anti-psoriatic activity was evaluated in-vivo using an imiquimod-induced psoriasis model.

Results: The OF achieved a particle size of 197.4 ± 9.47 nm, a PDI of 0.443 ± 0.025, a zeta potential of -44.4 ± 0.141mv, BD content of 105.85 ± 2.290%, SA content of 88.855 ± 2.920% with shear-thinning rheological behaviour and completed in-vitro drug release within 2-3 hours. The in-vivo studies confirmed the cubosomes' higher anti-psoriatic efficacy over the commercial product with lower changes in ear thickness, spleen to body weight ratio, psoriasis area severity index score and improved histopathological findings.

Conclusion: The developed BD SA-loaded cubosomes exhibit promising anti-psoriatic activity attributed to its nano-size and unique lipid content, with enhanced skin penetration and modified rheological properties; increasing the formulation's in-contact duration with the scalp resulting in lower application frequency and thus reduced BD and SA associated side effects.

Yousry, C., P. M. Zikry, H. M. Salem, E. B. Basalious, and O. N. El-Gazayerly, "Integrated nanovesicular/self-nanoemulsifying system (INV/SNES) for enhanced dual ocular drug delivery: statistical optimization, in vitro and in vivo evaluation.", Drug delivery and translational research, vol. 10, issue 3, pp. 801-814, 2020. Abstract

Ocular drug administration is usually problematic and suffers low bioavailability due to several physiological and biological factors that hinder their effective treatment. Terconazole (TZ) is considered as one of the effective ocular antifungal agents that is usually administrated intravitreally for higher efficacy. The aim of the work in this study is to formulate a TZ-loaded ocular drug delivery system with high efficiency and good tolerability. First, TZ-loaded bile-based nanovesicles (BBNV) were prepared and the formulation variables (namely, Span 60, cholesterol, and sodium deoxycholate levels) were optimized based on the results of the entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) using Box-Behnken statistical design. The optimized system was formulated using 73.59 mg Span 60, 1.28 mg cholesterol, and 3.11 mg sodium deoxycholate. The formulated system showed vesicles with PS of 526 nm, - 42.2 mV ZP, and 93.86% EE%. TZ release, cellular uptake, and cytotoxicity of the optimized system were evaluated in vitro. In addition, in vivo assessment of its safety was conducted histopathologically and via ocular irritation test to ensure the ocular tolerance of the system. Afterwards, the optimized TZ-loaded BBNV was integrated into a self-nanoemulsifying system (SNES) to allow faster TZ release for immediate antifungal effect, enhanced ocular residence, and improved ocular permeation. TZ release study revealed more than 2 folds increment in drug release rate from the integrated system compared to BBNV alone. Finally, this integrated system was assessed for its antifungal activity in vivo where it demonstrated higher antifungal activity against induced Candida albicans infection. Graphical abstract.

Salem, L. H., G. S. El-Feky, R. H. Fahmy, O. N. Elgazayerly, and A. A. Elbary, "Coated Lipidic Nanoparticles as a New Strategy for Enhancing Nose-to-Brain Delivery of a Hydrophilic Drug Molecule.", Journal of pharmaceutical sciences, vol. 109, issue 7, pp. 2237-2251, 2020. Abstract

Oral Almotriptan maleate (ALM) is used in the treatment of migraine; however, due to its extreme aqueous solubility, shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. Being flexible and lipophilic in nature, nanostructured lipid carriers (NLCs) represent a promising tool in delivering therapeutic substances to the brain. This investigation is meant to explore the capability of mucoadhesive chitosan-coated NLCs to efficiently deliver ALM to the brain through the nasal route as a non-invasive alternative route for targeting the central nervous system (CNS). D-optimal design was adopted and thirteen different formulae were prepared using hot homogenization and ultrasonication technique; where an accurate amount of the almotriptan was added to the molten lipid mixture followed by the addition of the heated aqueous phase under stirring, then the mixture was subjected to homogenization and ultrasonication. The prepared systems were then assessed for their particle size, PDI (polydispersity index), zeta potential (ZP), and entrapment efficiency (EE). The optimized selected formula; F1; composed of 50/50 Compritol/Labrafil and a co-mixture of 2:1 tween 80: Lauroglycol all coated in chitosan, showed a PS of 255 nm, PDI 0.27, ZP 34.1 mV, and 80% EE. A bi-phasic in vitro drug release pattern was obtained, enhanced mucoadhesive property and ex-vivo permeability through sheep nasal mucosa were attained. The In vivo studies performed on albino rabbits showed significantly higher C results in plasma of the optimized ALM-NLC (1.54 μg/mL) compared to those of IN ALM solution (0.25 μg/mL) and ALM oral tablet market product (0.58 μg/mL). Brain C were found to be 3.64 μg/mL, 0.5 μg/mL and 0.48 μg/mL for IN ALM-NLC, oral ALM market product and, IN ALM solution, respectively. Histopathological examination marked the formula as safe.

Yousry, C., P. M. Zikry, E. B. Basalious, and O. N. El-Gazayerly, "Self-nanoemulsifying System Optimization for Higher Terconazole Solubilization and Non-Irritant Ocular Administration.", Advanced pharmaceutical bulletin, vol. 10, issue 3, pp. 389-398, 2020. Abstract

Eye drops' formulations of poorly water-soluble drugs, offer the advantage of crossing the lipophilic cornea, but their limited aqueous solubility may lead to low ocular bioavailability limiting their therapeutic uses. Terconazole (TZ) is an antifungal drug with low aqueous solubility, restricting its application in ocular fungal infection. Thus, the aim of the work in this study is to enhance TZ solubilization, permitting better ocular permeation and higher bioavailability. To achieve this goal, different self-nanoemulsifying systems (SNESs) were prepared using different oils, surfactants and co-surfactants. Ternary phase diagrams were constructed to identify self nano-emulsification regions for each oil system examined; either Labrafil M2125CS or Capryol 90. TZ saturated solubility in the different formulated systems were measured and systems showing highest potential for TZ solubilization were selected. The optimized systems were chosen based on their globule size, polydispersity index, self-emulsification characteristics. Finally, TZ release as well as the irritation effect via Hen's Egg test-chorioallantoic membrane (HET-CAM test) of the optimized system was observed in vitro. The optimized system was formulated using 20% w/w Labrafil M2125 CS, 50% w/w Tween 80 and 30% w/w Transcutol HP. Oil globules showed size range of 15.13 nm and self-emulsification time of 12.80 seconds. The system released 100% of the drug within half an hour compared to 2 hours in case of TZ-suspension. Finally, HET-CAM test showed non-irritating response and normal vascularization of the chorioallantoic membrane. The formulated SNES could be a promising approach to enhance ocular efficacy of TZ.

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