El-bary, A. A., H. K. Ibrahim, and B. A. L. Q. E. E. S. S. A. E. E. D. HAZAA, "TOPICAL DRUG DELIVERY FOR EFFECTIVE TREATMENT OF BACTERIAL INFECTIONS OF THE ANTERIOR SEGMENT OF THE EYE", Asian Journal of Pharmaceutical and Clinical Research, vol. 11, issue 5, pp. 13-17, 2018.
Sakr, T. M., O. M. Khowessah, M. A. Motaleb, A. Abdel-Bary, M. T. El-Kolaly, and M. M. Swidan, "I-131 doping of silver nanoparticles platform for tumor theranosis guided drug delivery.", European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, vol. 122, pp. 239-245, 2018 Sep 15. Abstract

Nanotechnology may be applied in medicine where the utilization of nanoparticles (≤100 nm) for the delivery and targeting of theranostic agents is at the forefront of projects in cancer nano-science. This study points a novel one step synthesis approach to build up polyethylene glycol capped silver nanoparticles doped with I-131 radionuclide (I-doped Ag-PEG NPs). The formula was prepared with average hydrodynamic size 21 nm, zeta potential - 25 mV, radiolabeling yield 98 ± 0.76%, and showed good in-vitro stability in saline and mice serum. The in-vitro cytotoxicity study of cold Ag-PEG NPs formula as a drug carrier vehicle showed no cytotoxic effect on normal cells (WI-38 cells) at a concentration below 3 μL/10 cells. The in-vivo biodistribution pattern of I-doped Ag-PEG NPs in solid tumor bearing mice showed high radioactivity accumulation in tumor tissues with maximum uptake of 35.43 ± 1.12 and 63.8 ± 1.3% ID/g at 60 and 15 min post intravenous (I.V.) and intratumoral injection (I.T.), respectively. Great potential of T/NT ratios were obtained throughout the experimental time points with maximum ratios 45.23 ± 0.65 and 92.46 ± 1.02 at 60 and 15 min post I.V. and I.T. injection, respectively. Thus, I-doped Ag-PEG NPs formulation could be displayed as a great potential tumor nano-sized theranostic probe.

Elbary, A. A., H. F. Salem, R. A. Khallaf, and A. M. A. Ali, "Mucoadhesive niosomal in situ gel for ocular tissue targeting: in vitro and in vivo evaluation of lomefloxacin hydrochloride.", Pharmaceutical development and technology, vol. 22, issue 3, pp. 409-417, 2017 May. Abstract

Eradication of ophthalmic infections depends on increasing transcorneal permeation and localizing antibiotics at ocular surface. This study aimed at formulating lomefloxacin HCl (LF) in the form of niosomes and evaluating the in vivo performance of best formula in rabbits' eyes. Vesicles were developed by mixing three surfactants at three molar ratios of 1:1, 1:2 and 1:3 of surfactant to cholesterol. Size, zeta potential, release percentage, transcorneal permeation parameters, stability studies, cytotoxicity and antibacterial activity of niosomes were determined. Niosomes showed encapsulation efficiency of more than 78%, particle size below 500 nm and zeta potential below -43.6. The produced vesicles showed significantly higher amounts of drug permeated across cornea (166%) compared to LF solution. The in vivo study showed 2-5 folds increase in drug concentration in ocular fluids and tissues following administration of niosomes compared to marketed formula (from 3.75 to 10.31 mcg/mL in the cornea). Microbiological studies showed 35 folds increase in the antibacterial activity of LF niosomes compared to free drug; where MBC decreased from 31.25 mcg/mL in case of LF solution to 0.97 mcg/mL for niosomal gel. The formulated niosomes enhanced the ocular bioavailability of LF through increasing transcorneal permeation and localizing drug at site of action.

Ibrahim, I. T., M. T. El-Kolaly, M. H. Aboumanei, and A. Abdelbary, "(125)I labeling of clomiphene and biodistribution studies for possible use as a model in breast cancer imaging.", Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, vol. 115, pp. 37-44, 2016 Sep. Abstract

Clomiphene has growth-inhibitory effects of breast cancer cells, clomiphene was successfully labeled with (125)I via direct electrophilic substitution reaction with labeling yield 97%. It was obtained at optimum substrate amount of 0.5mg, Chloramine-T was used as an oxidizing agent at optimum amount of 25µg. Labeling reactions was done at pH 5 at ambient temperature. This study showed good in vitro and in vivo stability of the (125)I-clomiphene. The radiolabeled compound showed high ascetic fluid uptake of 18.12±0.27% at 30min post-injection. Solid tumor uptake of (125)I-clomiphene was 12.48±0.32% at 30min post-injection. This data revealed the localization of tracer in tumor tissue with high percent sufficient to use (125)I-clomiphene as a promising tool for the diagnosis of breast cancer.

Aboud, H. M., M. H. El Komy, A. A. Ali, S. F. Elmenshawe, and A. A. Elbary, "Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery.", AAPS PharmSciTech, vol. 17, issue 6, pp. 1353-1365, 2016 Dec. Abstract

Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to first-pass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 2(3) factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q 24) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.

Aboud, H. M., A. A. Ali, S. H. A. H. I. R. A. F. EL-MENSHAWE, and A. A. Elbary, "Nanotransfersomes of carvedilol for intranasal delivery: formulation, characterization and in vivo evaluation.", Drug delivery, vol. 23, issue 7, pp. 2471-2481, 2016 Sep. Abstract

CONTEXT: Development of carvedilol-loaded transfersomes for intranasal administration to overcome poor nasal permeability and hepatic first pass effect so as to enhance its bioavailability.

OBJECTIVE: The purpose of this study was to develop carvedilol-loaded transfersomes containing different edge activators (EAs) then evaluating the in vivo behavior of the optimized formula in rabbits.

METHODS: The vesicles were prepared by incorporating different EAs including Span 20, Span 60, Tween 20, Tween 80, and sodium deoxycholate (SDC) in the lipid bilayer and each EA was used in three different ratios with respect to phosphatidylcholine (PC) including 95:5%, 85:15%, and 75:25% w/w (PC:EA). Evaluation of transfersomes was carried out in terms of shape, size, entrapment efficiency (EE), in vitro release, ex vivo permeation, confocal laser scanning microscopy (CLSM), and stability studies. The pharmacokinetic study of the optimized formula was conducted in rabbits.

RESULTS: The mean diameter of the vesicles was in the range of 295-443 nm. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% where Span 60 gave the highest values. Whereas those prepared using 85:15% w/w ratio showed highest percentages of drug release where SDC was superior to other EAs. The developed transfersomes exhibited significantly higher amounts of carvedilol permeated through nasal mucosa. CLSM of formula T14 containing SDC with 85:15% (w/w) (PC:EA) ratio revealed high permeation across the nasal mucosa.

CONCLUSION: The nanotransfersomal vesicles were significantly more efficient in nasal delivery of carvedilol with absolute bioavailability of 63.4%.

Maher, E. M., A. M. A. H. Ali, H. F. Salem, and A. A. Abdelrahman, "In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids.", Drug delivery, vol. 23, issue 8, pp. 3088-3100, 2016 Oct. Abstract

Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5 s), fast dissolution (97% in 10 min) and optimum tensile strength (4.9 N/cm(2)). The results of in vivo data indicated high bioavailability (144 ng h/mL) and maximum plasma concentration (14.2 ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.

Khallaf, R. A., H. F. Salem, and A. A. Elbary, "5-Fluorouracil shell-enriched solid lipid nanoparticles (SLN) for effective skin carcinoma treatment.", Drug delivery, vol. 23, issue 9, pp. 3452-3460, 2016 Nov. Abstract

CONTEXT: The effective treatment of skin carcinoma is warranted for targeting the chemotherapeutic agents into tumor cells and avoiding unwanted systemic absorption.

OBJECTIVE: This work was dedicated to the purpose of engineering highly penetrating shell-enriched nanoparticles that were loaded with a hydrophilic chemotherapeutic agent, 5-fluorouracil (5-FU).

METHODS: Varying ratios of lecithin and poloxamer188 were used to produce shell-enriched nanoparticles by enabling the formation of reversed micelles within this region of the SLN. The localization of 5-FU within the shell region of the SLN, was confirmed using 5-FU nanogold particles as a tracer. SLN were introduced within sodium carboxy methylcellulose hydrogel, and then applied onto the skin of mice-bearing Ehrlich's ascites carcinoma. The mice were treated with the gel twice daily for 6 weeks.

RESULTS: The transmission electron microscope (TEM) revealed the formation of uniform nanoparticles, which captured reversed micelles within their shell region. The SLNs' had particle size that ranged from 137 ± 5.5 nm to 800 ± 53.6, zeta potential of -19.70 ± 0.40 mV and entrapment efficiency of 47.92 ± 2.34%. The diffusion of the drug-loaded SLN (269.37 ± 10.92 μg/cm(2)) was doubled when compared with the free drug (122 ± 3.09 μg/cm(2)) when both diffused through a hydrophobic membrane. SLN-treated mice exhibited reduced inflammatory reactions, with reduced degrees of keratosis, in addition to reduced symptoms of angiogenesis compared to 5-FU-treated mice.

CONCLUSION: SLN possesses the capacity to be manipulated to entrap and release hydrophilic antitumor drugs with ease.

Abd-elbary, A., A. M. A. Makky, M. I. Tadros, and A. A. Alaa-Eldin, "Laminated sponges as challenging solid hydrophilic matrices for the buccal delivery of carvedilol microemulsion systems: Development and proof of concept via mucoadhesion and pharmacokinetic assessments in healthy human volunteers.", European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, vol. 82, pp. 31-44, 2016 Jan 20. Abstract

Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa.

Abdelrahman, A. A., H. F. Salem, R. A. Khallaf, and A. M. A. H. Ali, "Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery", Journal of pharmaceutical innovation, vol. 10, pp. 254-268, 2015.
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