Abeer Kassem

Development of gastroretentive metronidazole floating raft system for targeting Helicobacter pylori.

The study demonstrates the feasibility of prolonging gastric residence time and release rate of metronidazole (Mz) by preparing floating raft system (FRS) using ion-sensitive in situ gel forming polymers. FRSs contained 3, 4, 5 and 0.5, 0.75, 1% w/v sodium alginate (Alg) and gellan gum (G), respectively, 0.25% w/v sodium citrate and calcium carbonate (C). Lipids: glyceryl mono stearate (GMS), Precirol(®) and Compritol(®) were incorporated into G-based formulations (G1%C1%). Mz:lipid ratio was 1:1, except for Mz:GMS, ratios of 1:1.5 and 1:2 were also investigated. Buoyancy, gelation capacity and viscosity parameters were evaluated. Drug release and kinetics for selected formulae were examined. The selected lipid containing formula was subjected to an accelerated stability testing. Alg4%C2% FRS exhibited short gelation lag time (3s), long duration (>24h), floating lag time 1m in and duration >24h, and a reliable sustained drug release (MDT 6h). Gellan gum FRSs achieved successful floating gastroretention, but failed to achieve the required gelation capacity. Incorporation of GMS (Mz:GMS 1:1) enhanced the gelation lag time and duration (6s and >24h, respectively), keeping sustained drug release and formulation stability. The improved characteristics of the selected FRS make them excellent candidates for gastric targeting to eradicate Helicobacter pylori.

Development of mucoadhesive microbeads using thiolated sodium alginate for intrapocket delivery of resveratrol

Resveratrol (Res), a polyphenolic phytoalexin, had shown a promising therapeutic efficacy towards treatment of periodontal disease in vitro. This work aims to develop Res microbeads with strong mucoadhesion using thiolated alginate (TA) for local treatment of periodontal pockets. TA was synthesized by conjugating sodium alginate (A) with thioglycolic acid. Product was evaluated by IR and DSC. Both A and A:TA Res microbeads with different ratios were prepared by ionotropic gelation method. Formulations were evaluated regarding their entrapment efficiency (%EE), swelling index (SI), in vitro drug release and kinetics. Selected formula was examined for its mucoadhesion by ex vivo wash-off method, surface morphology using scanning electron microscope (SEM) and stability against light. Clinical evaluation is running.Formation of TA was confirmed. %EE for all formulations ranged from 83.72 to 104.54%. Results revealed a significant lower SI for TA rich formulation (A/TA 1:1) along with slower release rate and zero-order kinetics, in addition to powerful mucoadhesion; 26% remaining of microbeads after 1h, compared to 2% for A microbeads. SEM micrographs showed a rough surface with drug precipitation. The formula maintained its %EE after 5h exposure to direct sunlight. A/TA 1:1 mucoadhesive Res microbeads could be exploited as a prolonged drug release devices for intrapocket application.

Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment

Abstract Introduction: Periodontal disease broadly defines group of conditions in which the supportive structure of the tooth (periodontium) is destroyed. Recent studies suggested that the anti-diabetic drug metformin hydrochloride (MF) has an osteogenic effect and is beneficial for the management of periodontitis. Objective: Development of strong mucoadhesive multiple layer film loading small dose of MF for intra-pocket application. Methodology: Multiple layer film was developed by double casting followed by compression method. Either 6% carboxy methyl cellulose sodium (CMC) or sodium alginate (ALG) constituted the inner drug (0.6%) loaded layer. Thiolated sodium alginate (TSA; 2 or 4%) constituted the outer drug free layers to enhance mucoadhesion and achieve controlled drug release. Optimized formulation was assessed clinically on 20 subjects. Results: Films were uniform, thin and hard enough for easy insertion into periodontal pockets. Based on water uptake and in vitro drug release, CMC based film with 4% TSA as an outer layer was the optimized formulation with enhanced mucoadhesion and controlled drug release (83.73% over 12 h). SEM showed the effective fabrication of the triple layer film in which connective lines between the layers could be observed. FTIR examination suggests possibility of hydrogen bonding between the –NH groups of metformin and –OH groups of CMC. DSC revealed the presence of MF mainly in the amorphous form. Clinical results indicated improvement of all clinical parameters six months post treatment. Conclusion: The results suggested that local application of the mucoadhesive multiple layer films loaded with metformin hydrochloride was able to manage moderate chronic periodontitis.

A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: Preparation, characterization and in vivo evaluation

ABSTRACT This work aimed at designing efficient safe delivery system for intranasal (IN) brain targeting of the water soluble anti‐ migraine drug Almotriptan malate (ALM). Solid lipid nanoparticles (SLNs) were prepared by w/o/w double emulsion‐solvent evaporation method. Selection of the optimized SLNs formula was based on evaluating particle size (PS), poly dispersity index (PDI) and entrapment efficiency (%EE). Optimized formula exhibited acceptable ranges; PS of 207.9nm, PDI of 0.41 and %EE of 50.81%. Poloxamer 407 (Plx) at different concentrations (16%, 18%, 20% w/v), with different mucoadhesive polymers (Carbopol‐974P, Na alginate, Na‐CMC) were evaluated for gelling time and temperature, pH and mucoadhesion. The chosen mucoadhesive in‐situ gel formula; 18% Plx 407 based‐0.75%w/v Na‐CMC, showed acceptable results, so that the optimized SLNs formula was further dispersed in it and evaluated for in vitro release, stability, in vivo and pharmacokinetics studies. Biomarkers’ evaluation and histopathological examination were also investigated. Results revealed rapid ALM brain delivery of the optimized formula; Brain/blood ratios at 10min. for NF (SLNs based IN in‐situ gel), ND (Free ALM IN in situ gel) and ALM i.v. (ALM IV solution) were 0.89, 0.19 and 0.31, respectively. Toxicological results confirmed the safety of NF for nasal administration. The achieved out comings are encouraging for further clinical trials of the developed system in humans in future research.

Platform for Lipid Based Nanocarriers’ Formulation Components and their Potential Effects: A Literature Review

BACKGROUND Lipid based nanocarriers have gained recently enormous interest for pharmaceutical application. They have the potential to provide controlled drug release and to target the drug to a specific area. In addition, lipid based nanocarriers can improve the bioavailability of drugs suffering from high hepatic first-pass metabolism, by enhancing their transport via the lymphatic system. The main components of lipid based nanocarriers are lipids and surfactants. Both have great influence on the prepared lipid based systems characteristics. The criteria for their selection are much related to physicochemical properties of the drug and the required administration route. This work gives an overview on the effect of both the type and amount of lipids and surfactants used in the manufacture of lipid based nanocarriers on their behavior and characteristics. CONCLUSION Recent studies revealed that the properties of the final product including; particle size, homogeneity, drug loading capacity, zeta potential, drug release profile, stability, permeability, pharmacokinetic properties, crystallinity and cytotoxicity, may be significantly influenced not only by the type but also the amount of the lipids and/or surfactants included in the formulation of the lipid based nanocarriers.

Topical simvastatin gel as a novel therapeutic modality for palatal donor site wound healing following free gingival graft procedure

Abstract Objective: Autogenous soft-tissue grafting is a commonly used procedure nowadays in dentistry. However, the prolonged healing time needed for the donor site leads to increase the patient’s pain and discomfort. Statin has been observed to be beneficial in reducing bacterial burden, improving epithelization and wound healing. The aim of this study was to evaluate intra-oral topical application of simvastatin/chitosan gel (10 mg/mL) over the palatal donor site following free gingival graft (FGG) procedure. Material and methods: Subjects indicated for FGG procedure were divided into four groups. Group I: Simvastatin suspension (S), group II: simvastatin/chitosan gel (SC), group III: chitosan gel (C), group IV: petroleum gel (P). Treatment was applied three times/day for the following 7 days. Wound healing was evaluated at day 3, 7 and 14 post-surgery. A visual analogue scale (VAS) was used to measure the experienced discomfort at 1, 3, 5, 7 and 14 days. Results: Statistical significant reduction in wound-healing scores was observed after 3 and 7 days for group II compared to other groups (p  = .015). A significant reduction was also observed in VAS score for group II compared to other groups at day 1, 3, 5 and 7. Conclusion: Topical application of S/C gel could be used as a novel therapeutic modality that improved healing and reduced pain in the palatal donor site following FGG procedure.