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Staff Researches

Azza Ahmed Mohamed Mahmoud

Norfloxacin-loaded collagen/chitosan scaffolds for skin reconstruction: Preparation, evaluation and in-vivo wound healing assessment

Azza Ahmed Mohamed Mahmoud

Mahmoud, A.A., Salama, A.H.

Eur J Pharm Sci

2015

Biomaterial scaffolds are versatile tools as drug carrier for treatment of wounds. A series of norfloxacin-loaded scaffolds were synthesized for treatment of wounds by combining collagen with two different types of chitosan using freeze-drying technique. Subsequently, scaffolds were screened in terms of morphology, water absorption and retention capacity, biodegradation, ex-vivo bioadhesive strength, in-vitro drug release biological compatibility, X-ray diffractometry, differential scanning calorimetry as well as in-vivo evaluation. The results indicate that the scaffold mechanical strength is dependent on the type of used chitosan. The prepared scaffolds contained interconnected porous architecture. The scaffolds had high water uptake and retention capacity with extended biodegradation rate. Scaffolds prepared with chitosan HCl showed superior bioadhesive strength compared to those prepared with low molecular weight chitosan. All scaffolds showed almost 100% drug release within 24 h. As identified by the terahertz pulsed imaging measurements, there is single scaffold area with the same concentration. After 28 days of wound dressing with selected norfoloxacin-loaded or unloaded collagen/chitosan scaffolds in Albino rats, it was found that the tissue regeneration time was fast compared to non-treated wounds. Furthermore, the drug-loaded scaffolds showed normal structure of an intact epidermal layer as well as the underlying dermis as revealed by histopathological studies. The obtained results suggest that the investigated norfloxacin-loaded collagen/chitosan scaffold is a potential candidate for skin regeneration application.

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Brinzolamide loaded-polymeric nanoparticles

Azza Ahmed Mohamed Mahmoud

Hamed A. Salama, M. Ghorab, Azza A. Mahmoud and Mayssa Abdel Hady

Current Science International

2016

The objective of the present study was to investigate the ability to formulate brinzolamide in the form of polylactic-co-glycolic acid (PLGA) nanoparticles. In this study brinzolamide-loaded nanoparticles were formulated according to the emulsification/solvent evaporation technique using the biodegradable PLGA. The effect of surfactant type and its percentage in the preparation were investigated. The investigated PLGA polymer with lactide: glycolide monomers’ ratio of 75:25 was able to develop PLGA vesicular system using the investigated surfactants. Brinzolamide-loaded nanoparticles prepared using PLGA with Pluronic acid F68 in the aqueous phase and 1 % Brij 97 in the organic phase showed the smallest particle size value (441.80 ± 72.97 nm). Brinzolamide-loaded nanoparticles prepared using PLGA with Pluronic acid F68 in aqueous phase and 2 % polysorbate 80 in organic phase had the largest encapsulation efficiency and drug loading values (47.86 ± 0.97 % and 38.76 %, respectively).

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Brinzolamide loaded-polymeric nanoparticles

Azza Ahmed Mohamed Mahmoud

Hamed A. Salama, M. Ghorab, Azza A. Mahmoud and Mayssa Abdel Hady

Current Science International

2016

The objective of the present study was to investigate the ability to formulate brinzolamide in the form of polylactic-co-glycolic acid (PLGA) nanoparticles. In this study brinzolamide-loaded nanoparticles were formulated according to the emulsification/solvent evaporation technique using the biodegradable PLGA. The effect of surfactant type and its percentage in the preparation were investigated. The investigated PLGA polymer with lactide: glycolide monomers’ ratio of 75:25 was able to develop PLGA vesicular system using the investigated surfactants. Brinzolamide-loaded nanoparticles prepared using PLGA with Pluronic acid F68 in the aqueous phase and 1 % Brij 97 in the organic phase showed the smallest particle size value (441.80 ± 72.97 nm). Brinzolamide-loaded nanoparticles prepared using PLGA with Pluronic acid F68 in aqueous phase and 2 % polysorbate 80 in organic phase had the largest encapsulation efficiency and drug loading values (47.86 ± 0.97 % and 38.76 %, respectively).

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Nano spray drying technique as a novel approach to formulate stable econazole nitrate nanosuspension formulations for ocular use

Azza Ahmed Mohamed Mahmoud

Maged, A., Mahmoud, A.A., Ghorab, M.M.

Mol. Pharm.

2016

The effect of using methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin as carriers for econazole nitrate nanoparticles prepared by nano spray dryer was explored in this work. Stabilizers, namely, poly(ethylene oxide), polyvinylpyrrolidone k30, poloxamer 407, Tween 80, and Cremophor EL, were used. The nano spray dried formulations revealed almost spherical particles with an average particle size values ranging from 121 to 1565 nm and zeta potential values ranging from −0.8 to −2.5 mV. The yield values for the obtained formulations reached 80%. The presence of the drug in the amorphous state within the nanosuspension matrix system significantly improved drug release compared to that for pure drug. Combination of hydroxypropyl-β-cyclodextrin with Tween 80 achieved an important role for preserving the econazole nanosuspension from aggregation during storage for one year at room temperature as well as improving drug release from the nanosuspension. This selected formulation was suspended in chitosan HCl to increase drug release and bioavailability. The in vivo evaluation on albino rabbit’s eyes demonstrated distinctly superior bioavailability of the selected formulation suspended in chitosan compared to its counterpart formulation suspended in buffer and crude drug suspension due to its mucoadhesive properties and nanosize. The nano spray dryer could serve as a one step technique toward formulating stable and effective nanosuspensions.

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Bioactive/natural polymeric scaffolds loaded with ciprofloxacin for treatment of osteomyelitis

Azza Ahmed Mohamed Mahmoud

Amany A. Mostafa, Mayyada M.H. El-Sayed, Azza A. Mahmoud, Amira M. Gamal-Eldeen

AAPS PharmSciTech

2016

Local delivery of antibiotic into injured bone is a demand. In this work, different scaffolds of chitosan (C) with or without bioactive glass (G) were prepared using the freeze-drying technique in 2:1, 1:1 and 1:2 weight ratios. Chitosan scaffolds and selected formulas of chitosan/bioglass were loaded with ciprofloxacin in 5, 10 and 20% w/w. Scaffold morphology showed an interconnected porous structure, where the glass particles were homogeneously dispersed in the chitosan matrix. The kinetic study confirmed that the scaffold containing 1:2 weight ratio of chitosan:glass (CG12) showed optimal bioactivity with good compromise between Ca and P uptake capacities and Si release rate. Chitosan / bioactive glass scaffolds showed larger t50 values indicating less burst drug release followed by a sustained drug release profile compared to those of chitosan scaffolds. The cell growth, migration, adhesion, and invasion were enhanced onto CG12 scaffold surfaces. Samples of CG12 scaffolds with or without 5% drug induced vascular endothelial growth factor (VEGF), while those containing 10% drug diminished VEGF level. Only CG12 induced the cell differentiation (alkaline phosphatase activity). In conclusion, CG12 containing 5% drug can be considered a biocompatible carrier which would help in the localized osteomyelitis treatment.

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Design and in-vitro/in-vivo evaluation of ultra-thin mucoadhesive buccal film containing fluticasone propionate

Azza Ahmed Mohamed Mahmoud

Ammar, H.O., Ghorab, M. and Mahmoud, A.A., Shahein, H.

AAPS PharmSciTech

2016

Fluticasone propionate is a synthetic corticosteroid drug distinguished by its potent anti-inflammatory action with low systemic side effects in comparison to other corticosteroids making it a potential drug for local buccal delivery. The aim of the present study was to design mucoadhesive buccal film containing fluticasone that is aesthetically acceptable and could maintain local drug release for a sustained period to manage the sign and symptoms of severe erosive mouth lesions. Solvent casting technique was used in film preparation. Different polymeric blends were used either alone or in combination with mucoadhesive polymers, sodium carboxymethyl cellulose (SCMC), or Carbopol 971P at different concentrations. The physicochemical properties, in vitro mucoadhesion time as well as the drug release properties for all prepared formulations were determined. Selected formulations with adequate properties were further examined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and subjected to in vivo evaluation. Films containing hydroxypropyl methylcellulose (HPMC)/ethyl cellulose (EC) showed acceptable physicochemical properties, homogenous drug distribution, convenient mucoadhesion time, moderate swelling as well as sustained drug release up to 12 h. The biological performance of these formulations was assessed on healthy human volunteers and compared with a prepared mouthwash which showed enhanced pharmacokinetic parameters for the selected films in comparison to the mouthwash. The results revealed that the optimized formulation containing HPMC/EC and 10% SCMC could successfully achieve sustained drug release for 10 h which is considered promising for local treatment of severe mouth lesions.

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Nanostructured lipid carriers as semisolid topical delivery formulations for diflucortolone valerate

Azza Ahmed Mohamed Mahmoud

Abdel-Salam, F. S., Mahmoud, A. A., Ammar, H. O. and Elkheshen, S. A.

J. Liposome Res.

2016

Context: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption. Objective: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption. Method: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol ATO5 or Tristearin as the solid lipid, CapryolTM or isopropyl myristate as the liquid lipid and Poloxamer 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs. Results and discussion: DFV-loaded NLC formulations possessed average particle size ranging from 160.40 nm to 743.7nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol and Labrafil M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12 h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation. Conclusion: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.

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Diflucortolone valerate loaded solid lipid nanoparticles as a semisolid topical delivery system

Azza Ahmed Mohamed Mahmoud

Abdel-Salam, F. S., Ammar, H. O., Elkheshen, S. A. and Mahmoud, A. A.

BFOPCU

2015

Solid lipid nanoparticles (SLNs) are promising delivery carriers that have been utilized for formulation and delivery of various drugs. For topical administration, they are usually incorporated into gel or cream to increase their residence time, which is time-consuming process and could affect their stability and characteristics. Preparation of solid lipid nanoparticles (SLNs)-based semisolid formulations could have potential pharmaceutical applications. The aim of this study was to formulate the corticosteroidal drug, diflucortolone valerate (DFV) into topical semisolid SLN formulations using a rapid cheap one-step process. SLN formulations were developed using a high-shear homogenization combined with sonication, using different types of solid lipids (e.g., Geleol®, Preciriol® ATO5, Tristearin® and Compritol® 888ATO) and Poloxamer® 407 as a surfactant. Selection of the lipids and using high lipid concentration were the key elements to get semisolid formulation immediately after sonication without incorporating the nanoparticles into a gel or a cream base. DFV SLN formulations possessed average particle size ranging from 203.71 ± 5.61 to 1421.00 ± 16.32 nm with a narrow size distribution and possessed shear thinning behavior. Incorporation of lipid based surfactants (Labrasol® or Labrafil®) was found to significantly increase DFV encapsulation efficiency (up to 45.79 ± 4.40%). Semisolid DFV-loaded SLN with high drug encapsulation efficiency and acceptable rheological behavior for topical preparation could be prepared in a one-step process.

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A novel method for preparing surface-modified fluocinolone acetonide loaded PLGA nanoparticles for ocular use: in vitro and in vivo evaluations

Azza Ahmed Mohamed Mahmoud

Salama, A.H., Mahmoud, A.A., Kamel, R.

AAPS PharmSciTech

2015

Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye

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Development and Evaluation of Floating Gastroretentive Microspheres for Modified Release of Risperidone

Azza Ahmed Mohamed Mahmoud

Ammar, H. O., Ghorab, M. M., Mahmoud, A. A. and Noshi, S.H.

Inventi Rapid: Pharm Tech

2015

The present work was carried out to prepare and evaluate floating microspheres of the model antipsychotic drug, risperidone, using various viscosity grades of polymers such as polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC). Floating microspheres were prepared by emulsion solvent diffusion technique using Eudragit S100, compritol 888 ATO and hydroxypropyl methyl cellulose (HPMC E15 and E50) or polyvinylpyrrolidone (PVP K25, K30 and K90). The prepared formulations were examined by scanning electron microscope and were also characterized for their yield value, drug loading, floating behavior as well as in-vitro drug release pattern. Floating microspheres were found to be hollow spherical with smooth surfaces. Using high viscosity grade of HPMC in formulating floating microspheres demonstrated more pronounced increase in the microsphere yield and drug loading values and resulted in more sustained drug release as well as high buoyancy percentage value at the end of 12 hr. The formula containing 5% risperidone, 50% eudragit S100, 30% compritol 888 ATO and 15% HPMC E50 showed good balance between buoyancy and prolonged drug release over 12 hours.

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Injectable nano-amorphous calcium phosphate based in-situ gel systems for treatment of periapical lesions

Azza Ahmed Mohamed Mahmoud

Mostafa, A., Zaazou, M., Chow, L., Mahmoud, A. A., Zaki, D., Basha, M., Abdel Hamid, M., Sharaf, N., Khallaf, M. and Hamdy, T.

Biomedical Materials

2015

Nonsurgical local treatment of a periapical lesion arising from trauma or bacterial infection is a promising innovative approach. The present study investigated the feasibility of developing injectable amorphous calcium phosphate nanoparticles (ACP NPs) and ACP NPs loaded with an anti-inflammatory drug; ibuprofen (IBU-ACP NPs) in the form of thermoreversible in situ gels to treat periapical lesions with the stimulation of bone formation. NPs were produced by a spray-drying technique. Different formulations of Poloxamer 407 were incorporated with/without the produced NPs to form injectable gels. A drug release study was carried out. A 3 month in vivo test on a dog model also was assessed. Results showed successful incorporation of the drug into the NPs of CP during spray drying. The particles had mean diameters varying from 100 to 200 nm with a narrow distribution. A drug release study demonstrated controlled IBU release from IBU-ACP NPs at a pH of 7.4 over 24 h. The gelation temperature of the injectable in situ gels based on Poloxamer 407 was measured to be 30 °C. After 3 months of implantation in dogs, the results clearly demonstrated that the inclusion of ACP NPs loaded with IBU showed high degrees of periapical bone healing and cementum layer deposition around the apical root tip.

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ISACB6 Nantes France

Azza Ahmed Mohamed Mahmoud

France

2013

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