Ahmed, S., O. Saher, H. Attia, A. M. Fahmy, and I. M. Adel, "Development and characterization of fenticonazole nitrate-loaded cubogel for the management of vaginal candidiasis.", International journal of pharmaceutics: X, vol. 10, pp. 100355, 2025 Dec. Abstract

Vaginal candidiasis is a medical condition that affects large majority of the women at least once in their lifetime. The condition manifests with itching, irritation, and discharges which is troublesome for women during mundane activities. The purpose of this research was to formulate and evaluate the physicochemical properties and drug permeation of Fenticonazole-loaded cubogel through vaginal mucosa. Concisely, the drug-loaded cubosomes were prepared via hot dispersion emulsification technique. Following, the percent drug entrapment efficiency, particle size, polydispersity index, and zeta potential of the cubosomes were determined. Optimization criteria involved maximizing entrapment efficiency (EE %) and zeta potential (ZP), while maintaining a nanoscale particle size to ensure colloidal stability. The optimized formulation exhibited a high desirability score of 0.933 with EE % of 85.32 2.34 %, PS of 169 0.85 nm, PDI of 0.29 0.02, and ZP of -24.40 1.27 mV. In addition, 86.77 3.79 % of Fenticonazole nitrate was released from the optimum cubosomal formulation after 8 h. Cubical nanovesicles were revealed via transmission electron microscope while infrared spectroscopy revealed the lack of interaction between the used components. Stability was unchanged upon storage for three months. The rheogram of the optimum formulation-loaded cubogel suggested a shear-thinning behavior. Additionally, the optimum cubogel demonstrated higher biofilm inhibitory effect compared to the drug suspension. Similarly, both, ex vivo permeation and confocal laser scanning, suggested the enhanced vaginal epithelium permeability and the deeper vaginal mucosa penetration of the optimum cubogel, compared to the drug suspension and aqueous Rhodamine B carbopol gel, respectively. Histopathological assessment concluded with the safety of the cubogel on the vaginal mucosal epithelium and underlying tissue.

rofida albash, A. M. Fahmy, H. A. Shamsel-Din, ahmed b ibrahim, H. A. Bogari, R. T. Malatani, M. A. Abdelbari, and S. Mosallam, "Intranasal propranolol hydrochloride-loaded PLGA-lipid hybrid nanoparticles for brain targeting: Optimization and biodistribution study by radiobiological evaluation.", European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, vol. 208, pp. 107061, 2025 May 01. Abstract

The present work aimed to load propranolol hydrochloride (PN), a beta-blocking agent with low oral bioavailability, into PLGA-lipid hybrid nanoparticles (PLHNPs) for augmenting its efficacy. PLHNPs contain phospholipid (PC) in addition to PLGA to augment the potential of PLGA nanoparticles in the intranasal delivery and PN avoidance of the blood-brain barrier for the management of migraine. PLHNPs were prepared by single emulsion/ solvent evaporation method and then optimized by applying 2 full factorial design using PC amount (mg) (X), PLGA amount (mg) (X), and surface active agent type (X) as independent variables, whilst their effect was inspected for entrapment efficiency percent (EE%) (Y) and particle size (PS) (Y). Design-Expert® was utilized to choose the optimum PLHNPs for more explorations. The optimum PLHNPs formulation (F2) had EE% of 78.00 ± 0.71 %, PS of 104.50 ± 2.04 nm, polydispersity index of 0.429 ± 0.033, and zeta potential of 23.70 ± 0.10 mV. The optimum PLHNPs formulation was stable for up to 90 days. Moreover, it showed a sustained release profile compared to PN solution. It also showed a spherical shape under a transmission electron microscope. The optimized PN-loaded PLHNPs formulation was radio formulated with radiolabeled isotope ([Tc]Tc) in maximum radiolabeling yield (91.40 ± 1.85 %) of [Tc]Tc-PLHNPs to be used in radiological evaluation for in-vivo biodistribution and brain targeting after oral and intranasal administration. [Tc]Tc-PLHNPs showed higher brain targeting (5.80 ± 0.12 % ID/g) with a high brain-to-blood ratio of (2.42 ± 0.14) at 0.5 h after intranasal administration in addition to controlled blood levels and sustained release up to 8 h that confirm the efficacy of PLHNPs for brain targeting.

Ahmed, S., H. Attia, O. Saher, and A. M. Fahmy, "Augmented glycerosomes as a promising approach against fungal ear infection: Optimization and microbiological, and assessments.", International journal of pharmaceutics: X, vol. 8, pp. 100295, 2024. Abstract

In the current study, voriconazole (VCZ) augmented glycerosomes were optimized for topical otomycosis management according to a 2 factorial design, employing a thin film hydration method. By optimizing Glycerol volume, limonene: VCZ ratio and Span® 60: soybean phosphatidyl choline (PC) ratio, glycerosomes with maximum percentage entrapment efficiency (%EE) and zeta potential (ZP) and minimum vesicle size (VS) and polydispersity index (PDI) were to be obtained. An optimal augmented glycerosomal formula (OAG) that contained 10 mg VCZ, 150 mg PC, and 3 mL glycerol, comprising 2.5: and 0.92:1 ratios of the latter two independent variables, was proposed via numerical optimization. OAG exhibited high %EE and ZP values and acceptable low values for VS and PDI (84.3 ± 2.0 %, -38.8 ± 1.8 mV, 191.0 ± 1.1 nm, and 0.192 ± 0.01, respectively). Extensive in testing of OAG revealed the entrapment of VCZ within OAG, biphasic in release profile, stability for up to 3 months at 2-8 °C and spherical morphology of OAG with VS like that obtained via zetasizer. OAG demonstrated higher permeated amounts of VCZ and flux values than VCZ suspension, leading to an enhancement ratio of 2.56 in the permeation study. The deeper penetration ability of OAG demonstrated by Confocal Laser Scanning Microscopy and its superior in antifungal activity confirmed the validity of the study. Also, the histopathological study confirmed the safety of OAG for topical use, suggesting that VCZ OAG was a promising topical antimycotic formula.

rofida albash, R. M. El-Dahmy, M. I. A. Hamed, K. M. Darwish, A. M. Alahdal, A. B. Kassem, and A. M. Fahmy, "Repurposing levocetirizine hydrochloride loaded into cationic ceramide/phospholipid composite (CCPCs) for management of alopecia: central composite design optimization, and studies.", Drug delivery, vol. 29, issue 1, pp. 2784-2795, 2022. Abstract

Levocetirizine hydrochloride (LVC) is an antihistaminic drug that is repurposed for the treatment of alopecia. This investigation is targeted for formulating LVC into cationic ceramide/phospholipid composite (CCPCs) for the management of alopecia. CCPCs were fabricated by ethanol-injection approach, through a central composite experiment. CCPCs were evaluated by inspecting their entrapment efficiency (EE%), polydispersity index (PDI), particle size (PS), and zeta potential (ZP). The optimum CCPCs were additionally studied by , , , and studies. The fabricated CCPCs had acceptable EE%, PS, PDI, and ZP values. The statistical optimization elected optimum CCPCs composed of 5 mg hyaluronic acid, 10 mg ceramide III, and 5 mg dimethyldidodecylammonium bromide employing phytantriol as a permeation enhancer. The optimum CCPCs had EE%, PS, PDI, and ZP of 88.36 ± 0.34%, 479.00 ± 50.34 nm, 0.377 ± 0.0035, and 20.20 ± 1.13 mV, respectively. The optimum CCPC maintained its stability for up to 90 days. It also viewed vesicles of tube shape via transmission electron microscope. The assessment resulted in better interaction and stability between LVC and vesicle components in water. The and assessments showed satisfactory skin retention of LVC from optimum CCPCs. The histopathological assessment verified the safety of optimum CCPCs to be topically applied. Overall, the optimum CCPCs could be utilized as a potential system for the topical management of alopecia, with a prolonged period of activity, coupled with reduced LVC shortcomings.

rofida albash, A. M. Fahmy, M. I. A. Hamed, K. M. Darwish, and R. M. El-Dahmy, "Spironolactone hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism: studies, statistical optimization, and studies.", Drug delivery, vol. 28, issue 1, pp. 2289-2300, 2021. Abstract

Spironolactone (SP) is a potassium sparing diuretic with antiandrogenic properties. This study aimed at formulating SP into hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism. HAECs were prepared by ethanol injection method, according to D-optimal design, after a proper study. HAECs were evaluated by measuring their entrapment efficiency (EE%), particle size (PS), and polydispersity index (PDI). Optimal hyaluronic acid enriched cerosomes (OHAECs) were subjected to further and and studies. The study concluded better interactions between SP and phosphatidyl choline in presence of hyaluronic acid (HA) and high stability of their binding in water. The prepared HAECs had acceptable EE%, PS, and PDI values. The statistical optimization process suggested OHAEC containing 10.5 mg ceramide III and 15 mg HA, utilizing Kolliphor RH40. OHAEC had EE% and PS of 89.3 ± 0.3% and 261.8 ± 7.0 nm, respectively. OHAEC was stable for up to 3 months. It also showed a mixed tubular and vesicular appearance under transmission electron microscope. The and studies concluded better skin deposition and accumulation of SP from OHAEC. The histopathological study demonstrated the safety of OHAEC for topical application. Therefore, OHAEC could be considered as effective system for topical application of SP to manage hirsutism, with prolonged action, coupled with minimized side effects.

Fahmy, A. M., M. Hassan, D. A. El-Setouhy, S. A. Tayel, and A. M. Al-mahallawi, "Voriconazole Ternary Micellar Systems for the Treatment of Ocular Mycosis: Statistical Optimization and In Vivo Evaluation.", Journal of pharmaceutical sciences, 2020. Abstract

Voriconazole (VRC) is a broad spectrum, second generation triazole antifungal. The main use of VRC is via the oral and intravenous route. The study aimed to formulate VRC into ternary micellar systems (TMSs) for the topical treatment of ocular mycosis. TMSs were successfully prepared by water addition/solvent evaporation method, applying a 3-factor D-optimal design. The numerical optimization process suggested an optimal formula (OTMS) composed of total Pluronics to drug weight ratio of 22.89: 1, 1:1 weight ratio of Pluronic® P123 and F68, and 2% w/v of Labrasol. OTMS had high solubilization efficiency of 98.0%, small micellar size of 21.8 nm and suitable zeta potential and polydispersity index values of -9.0 mV and 0.261, respectively. OTMS exhibited acceptable stability for 3 months. Transmission electron microscopy demonstrated the spherical morphology of micelles. OTMS was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OTMS for ocular use. The fungal susceptibility testing using Candida albicans demonstrated the superiority of OTMS to VRC suspension, with greater and more durable growth inhibition. Therefore, ocular application of optimized VRC-loaded TMSs can be a promising treatment for ocular mycosis.

Fahmy, A. M., M. Hassan, D. A. El-Setouhy, S. A. Tayel, and A. M. Al-mahallawi, "Statistical optimization of hyaluronic acid enriched ultradeformable elastosomes for ocular delivery of voriconazole via Box-Behnken design: characterization and evaluation.", Drug delivery, vol. 28, issue 1, pp. 77-86, 2021. Abstract

Voriconazole (VCZ) is a well-known broad spectrum triazole antifungal, mainly used orally and intravenously. The study aimed to formulate VCZ into ultradeformable elastosomes for the topical treatment of ocular fungal keratitis. Different formulae were prepared using a modified ethanol injection method, employing a 3 Box-Behnken design. They were characterized by measuring their entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The optimized formula was subjected to further investigations and evaluation studies. The prepared vesicles had satisfactory EE%, PS, PDI and ZP values. The numerical optimization process suggested an optimal elastosomal formula (OE) composed of phosphatidyl choline and brij S100 at the weight ratio of 3.62: 1, 0.25%w/v hyaluronic acid and 5% (percentage from phosphatidyl choline/brij mixture) polyvinyl alcohol. It had high EE (72.6%), acceptable PS and PDI (362.4 nm and 0.25, respectively) and highly negative ZP of -41.7 mV. OE exhibited higher elasticity than conventional liposomes, with acceptable stability for three months. Transmission electron microscopy demonstrated the spherical morphology of vesicles with an external transparent coat of Hyaluronic acid. OE was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OE for ocular use. The fungal susceptibility testing using demonstrated the superiority of OE to VCZ suspension, with greater and more durable growth inhibition. Therefore, OE can be regarded as a promising formula, achieving both safety and efficacy.

Fahmy, A. M., D. A. El-Setouhy, B. A. Habib, and S. A. Tayel, "Enhancement of Transdermal Delivery of Haloperidol via Spanlastic Dispersions: Entrapment Efficiency vs. Particle Size.", AAPS PharmSciTech, vol. 20, issue 3, pp. 95, 2019 Jan 29. Abstract

Haloperidol (Hal) is a well-known typical antipsychotic. Hepatic first pass metabolism leads to its limited oral bioavailability. This study aimed at enhancing transdermal delivery of Hal via spanlastic formulae. Hal-loaded spanlastics of Span®60 and an edge activator (EA) were successfully prepared by ethanol injection method according to a 3.4 full factorial design. In this design, independent variables were X, EA type, and X, Span®60 to EA ratio. Y, percentage entrapment efficiency (EE%); Y, particle size (PS); Y, deformability index (DI); and Y, percentage drug released after 4h (Q4h), were chosen as dependent variables. The Fourier-transform infrared spectral analysis showed no considerable chemical interaction between Hal and the used excipients. Both factors affected significantly all the responses except DI. Desirability of each prepared formula was calculated based on maximizing EE% and Q4h and minimizing PS. Formula F6, with X, Tween®80, and X, 8:2, had the highest desirability value followed by F7, with X, Tween®80, and X, 6:4, and both were chosen as selected formulae (SF) for further investigation. F6 (having more entrapped Hal), F7 (of smaller PS), and Hal solution in propylene glycol were subjected to ex vivo permeation test through newborn rat skin. Both formulae showed marked enhancement in drug permeation compared with drug solution. The significantly higher Q and J of F7 from F6 may indicate that the smaller particle size aided more than higher entrapment in achieving a higher permeation for Hal of 3.5±0.2μg/cm.h. These results are promising for further investigation of this formula.

Fahmy, A. M., D. A. El-Setouhy, ahmed b ibrahim, B. A. Habib, S. A. Tayel, and N. A. Bayoumi, "Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies.", Drug delivery, vol. 25, issue 1, pp. 12-22, 2018 Nov. Abstract

Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L - made of Span 60 and Tween 80 at the weight ratio of 4:1 along with 1% w/v Labrasol - as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of diluted formula with 50 µl saline having 200 MBq of Tc and containing 13.6 mg of reducing agent (NaBH) and volume completed to 300 µl by saline at pH 10 for 10 min as reaction time. The biodistribution study showed that the transdermal Tc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral Tc-SF dispersion. So, transdermal hydrogel of SF may be considered a promising sustained release formula for Hal maintenance therapy with reduced dose size and less frequent administration than oral formula.

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