El-helaly, S. N., K. A. Amr, M. Fadel, and R. H. Fahmy, "Fluticasone propionate zein nanoparticles - Loaded in situ gelling system: in vitro/ex vivo studies and associated in vivo nasal MMP9 suppressed effect", Journal of Drug Delivery Science and Technology, vol. 96, 2024.
Adel, S., R. H. Fahmy, I. Elsayed, M. I. Mohamed, and R. R. Ibrahim, "Fabrication and optimization of itraconazole-loaded zein-based nanoparticles in coated capsules as a promising colon-targeting approach pursuing opportunistic fungal infections.", Drug delivery and translational research, vol. 13, issue 12, pp. 2982-3002, 2023. Abstract

Itraconazole (ITZ), a broad-spectrum antifungal drug, was formulated into colon-targeting system aiming to treat opportunistic colonic fungal infections that commonly infect chronic inflammatory bowel diseases (IBD) patients due to immunosuppressive therapy. Antisolvent precipitation technique was employed to formulate ITZ-loaded zein nanoparticles (ITZ-ZNPs) using various zein: drug and aqueous:organic phase ratios. Central composite face-centered design (CCFD) was used for statistical analysis and optimization. The optimized formulation was composed of 5.5:1 zein:drug ratio and 9.5:1 aqueous:organic phase ratio with its observed particle size, polydispersity index, zeta potential, and entrapment efficiency of 208 ± 4.29 nm, 0.35 ± 0.04, 35.7 ± 1.65 mV, and 66.78 ± 3.89%, respectively. ITZ-ZNPs were imaged by TEM that revealed spherical core-shell structure, and DSC proved ITZ transformation from crystalline to amorphous form. FT-IR showed coupling of zein NH group with ITZ carbonyl group without affecting ITZ antifungal activity as confirmed by antifungal activity test that showed enhanced activity of ITZ-ZNPs over the pure drug. Histopathological examination and cytotoxicity tests ensured biosafety and tolerance of ITZ-ZNPs to the colon tissue. The optimized formulation was then loaded into Eudragit S100-coated capsules and both in vitro release and in vivo X-ray imaging confirmed the success of such coated capsules in protecting ITZ from the release in stomach and intestine while targeting ITZ to the colon. The study proved that ITZ-ZNPs is promising and safe nanoparticulate system that can protect ITZ throughout the GIT and targeting its release to the colon with effectual focused local action for the treatment of colon fungal infections.

Adel, S., R. H. Fahmy, I. Elsayed, M. I. Mohamed, and R. R. Ibrahim, "Exploiting itraconazole-loaded nanomixed micelles in coated capsules as efficient colon-targeted delivery system for improved antifungal and potential anticancer efficacy.", Pharmaceutical development and technology, vol. 28, issue 3-4, pp. 333-350, 2023. Abstract

Chronic Inflammatory bowel diseases are usually accompanied by opportunistic colonic fungal infections. Itraconazole (ITZ), is a highly lipophilic broad-spectrum antifungal drug that is superiorly effective against several fungal species. Box-Behnken design was adopted to design ITZ-nanomixed micelles (ITZ-NMMs), aiming to enhance ITZ solubility, using various concentrations of Pluronic® L121, Cremophor EL, and with either sodium-deoxycholate or Pluronic F68 through thin film hydration technique. Optimized formula composed of 90 % Pl-L121, 9.1% Cremophor EL, 3.127 % ITZ concentration and SDC as the hydrophilic surfactant and its particle size, Polydispersity index, zeta potential, entrapment efficiency, and release extent after 3 h were found to be 17.82 ± 0.189 nm, 0.26 ± 0.014, -6.72 ± 0.725 mV, 66 ± 7.4%, and 96.3 ± 7.22%, respectively. ITZ release study implied the ability of optimal ITZ-NMMs to enhance ITZ solubility in comparison to ITZ suspension. Also, augmented anti-fungal and anti-cancer activities were proven as ITZ-NMMs IC was 16.5 times that of pure ITZ. Afterwards, lyophilized optimal ITZ-NMMs formula was loaded into Eudragit S100-coated capsules where release and X-ray imaging ensured protection of ITZ release in either the stomach or intestine and targeting it to the colon. Such results suggested promising ITZ-NMMs system, capable of enhancing ITZ solubility in the intended target site, therefore, can be used not only in the treatment of colon fungal infections but also augments colon cancer therapy.

El-helaly, S. N., E. Abd-Elrasheed, S. A. Salim, R. H. Fahmy, S. Salah, and M. M. EL-Ashmoony, "Green Nanotechnology in the Formulation of a Novel Solid Dispersed Multilayered Core-Sheath Raloxifene-Loaded Nanofibrous Buccal Film; In Vitro and In Vivo Characterization", Pharmaceutics, vol. 13, issue 3, pp. 474, 2021.
Ali, M. S., A. A. Metwally, R. H. Fahmy, and R. Osman, "Chitosan-coated nanodiamonds: Mucoadhesive platform for intravesical delivery of doxorubicin.", Carbohydrate polymers, vol. 245, pp. 116528, 2020. Abstract

Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them for efficient loading with various drugs. However, NDs easily scavenge ions upon mixing with physiological media leading to rapid aggregation. Herein, chitosan was employed to endue steric stabilization to NDs and confer adhesiveness to the particles improving their retention in the urinary bladder. The effect of chitosan molecular weight and pH on the particle size and surface charge of chitosan-coated doxorubicin-loaded NDs (Chi-NDX) was investigated. Selected formula exhibited high drug loading efficiency (>90 %), small particle size (<150 nm), good colloidal stability, acid-favored drug release but limited stability in cell culture media. After further stabilization with TPP or dextran sulfate, selected TPP-treated formula displayed more potent cytotoxic effect compared with free doxorubicin and uncoated nanoparticles, and higher drug retention in ex vivo bovine bladder. Therefore, TPP-Chi-NDX is suggested as a promising system for mucosal anticancer delivery.

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.

Ali, M. S., A. A. Metwally, R. H. Fahmy, and R. Osman, "Nanodiamonds: Minuscule gems that ferry antineoplastic drugs to resistant tumors.", International journal of pharmaceutics, vol. 558, pp. 165-176, 2019. Abstract

Remarkable efforts are currently devoted to the area of nanodiamonds (NDs) research due to their superior properties viz: biocompatibility, minute size, inert core, and tunable surface chemistry. The use of NDs for the delivery of anticancer drugs has been at the forefront of NDs applications owing to their ability to increase chemosensitivity, sustain drug release, and minimize drug side effects. Accelerated steps towards the move of NDs from bench side to bedside have been recently witnessed. In this review, the effects of NDs production and purification techniques on NDs' final properties are discussed. Special concern is given to studies focusing on NDs use for anticancer drug delivery, stability enhancement and mediated targeted delivery. The aim of this review is to put the results of studies oriented towards NDs-mediated anticancer drug delivery side by side such that the reader can assess the potential use of NDs in clinics and follow up the upcoming results of clinical testing of NDs on animals and humans.

ElShagea, H. N., N. A. Elkasabgy, R. H. Fahmy, and E. B. Basalious, "Freeze-Dried Self-Nanoemulsifying Self-Nanosuspension (SNESNS): a New Approach for the Preparation of a Highly Drug-Loaded Dosage Form.", AAPS PharmSciTech, vol. 20, issue 7, pp. 258, 2019. Abstract

Febuxostat suffers from relatively low bioavailability owing to the poor drug solubility and hepatic first-pass effect. This study aimed to prepare highly drug-loaded self-nanoemulsifying self-nanosuspension systems (SNESNS). SNESNS were designed to improve febuxostat's oral bioavailability by enhancing its solubility. Different oil and surfactant/co-surfactant mixtures were used for the preparation of SNESNS. The prepared SNESNS were estimated for their particle size, in vitro drug release and transmission electron microscopy (TEM). Results revealed that the oil mixture of Capryol™ 90:Miglyol 812 (1:1 w/w) with surfactant/co-surfactant mixture of Cremophor RH 40/Transcutol HP loaded with drug in 4-fold greater concentration than its saturated solubility resulted in the formation of SNESNS by dilution under the effect of magnetic stirring. SNESNS were freeze-dried using trehalose as a cryoprotectant. TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Higher C and AUC values compared to those of the market product Feburic tablets confirmed the success of the SNESNS as a promising carrier for drugs suffering from poor water solubility like febuxostat.

El Sharkawi, F. Z., S. M. Ewais, R. H. Fahmy, and L. A. Rashed, "PTEN and TRAIL genes loaded zein nanoparticles as potential therapy for hepatocellular carcinoma.", Journal of drug targeting, vol. 25, issue 6, pp. 513-522, 2017 Jul. AbstractWebsite

Gene therapy is one of the recent approaches in treatment of hepatocellular carcinoma (HCC). Development of a vector or vehicle that can selectively and efficiently deliver the gene to target cells with minimal toxicity is an urgent demand. In the present study, phosphatase and tensin homolog (PTEN) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) genes were loaded to zein nanoparticles (ZNPs). The formulated PTEN and TRAIL-loaded ZNPs were tested for their in vitro and in vivo potential antitumor efficacy using liver tumor cells (HepG2) and HCC-induced rats as animal model. Also, mRNA expression of p53, VGEF and MMP-2 were carried out as markers of apoptosis, angiogenesis and metastasis in animal liver tissues. The results of the study showed that both PTEN and TRAIL-loaded ZNPs proved anti-proliferative activity against HepG2 cell lines with ICvalues of 0.09, 0.25 µg/ml, respectively. In vivo assay confirmed decrease in mRNA expression of both VEGF and MMP-2 with increased in P53 expression level in liver tissues of the treated animals. Therefore, authors introduced new integration between gene therapy and nanotechnology in the form of PTEN and TRAIL-loaded ZNPs that proved potential to be used in gene therapy for the treatment of HCC.

Gamal, W., R. H. Fahmy, and M. I. Mohamed, "Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits.", Drug development and industrial pharmacy, vol. 43, issue 9, pp. 1539-1547, 2017 Sep. AbstractWebsite

OBJECTIVE: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.

METHODS: Liquid SNEDDS (L-SNEDDS) composed of Capryol™ 90 (oil), CremophorRH40 (surfactant), and TranscutolHP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.

RESULTS: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in t, AUC, and AUCat p < .05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product.

CONCLUSIONS: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability.

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