Papers by Rania Aziz Ishak
RPS Pharmacy and Pharmacology Reports
Objective The current review gives an overview on the anatomical and cellular structure of the na... more Objective The current review gives an overview on the anatomical and cellular structure of the nasal cavity. It presents some possibilities and different techniques to enhance the drug penetration through the nasal barrier. It comprehensively details the intranasal drug delivery system and the treatment modalities of hypertension, with emphasis on nanotechnology-based products. Methods Gather published works about the research progression in the systemic delivery of antihypertensive drugs through the nasal epithelium, the formulation tactics and their related in vitro, ex vivo and in vivo assessment technologies in this field. Key findings Intranasal drug delivery is one of the potential routes for avoiding the first pass effect, lowering drug doses, reducing systemic side effects of most antihypertensive drugs and enhancing drug bioavailability. Conclusions Compared to oral medications, nasal medications often have better bioavailability and fewer adverse effects at the same dosage...
Pharmaceutics
10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of n... more 10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of novel fatty acid vesicles for comparison with oleic acid (OA) ufasomes. The vesicles were loaded with magnolol (Mag), a potential natural drug for skin cancer. Different formulations were prepared using the thin film hydration method and were statistically evaluated according to a Box–Behnken design in terms of particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The ex vivo skin permeation and deposition were assessed for Mag skin delivery. In vivo, an assessment of the optimized formulae using 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer in mice was also conducted. The PS and ZP of the optimized OA vesicles were 358.9 ± 3.2 nm and −82.50 ± 7.13 mV compared to 191.9 ± 6.28 nm and −59.60 ± 3.07 mV for HDA vesicles, respectively. The EE was high (>78%) for both types of vesicles. Ex vivo permeation studies revealed enhanced Ma...
Pharmaceutics
To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thor... more To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thoroughly reconnoitered, yet they have been extensively used. LCNs are primarily made up of glyceryl monooleate (GMO) or phytantriol as a lipid, a stabilizing agent, and a penetration enhancer (PE). For optimization, the D-optimal design was exploited. A characterization using TEM and XRPD was conducted. Optimized LCNs were loaded with the anti-glaucoma drug Travoprost (TRAVO). Ex vivo permeation across the cornea, in vivo pharmacokinetics, and pharmacodynamic studies were performed along with ocular tolerability examinations. Optimized LCNs are constituted of GMO, Tween® 80 as a stabilizer, and either oleic acid or Captex® 8000 as PE at 25 mg each. TRAVO-LNCs, F-1-L and F-3-L, showed particle sizes of 216.20 ± 6.12 and 129.40 ± 11.73 nm, with EE% of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively, revealing the highest drug permeation parameters. The bioavailability of both attained 106.1% an...
International Journal of Pharmaceutics
Journal of Pharmacy & Pharmaceutical Sciences, 2015
Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric re... more Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric residence and a drug release independent of patient related variables. It is usually useful in improving local gastric treatment as well as overcoming drug-related problems .i.e. drugs having narrow absorption window, short half-life or low intestinal solubility. Buoyancy is considered one of the most promising approaches for gastro-retention of dosage forms. Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach causing an increase in gastric residence time. The buoyancy of these systems is attained by the aid of substances responsible to generate the low density. Various agents with different mechanisms were adopted either gas-generating agents, air entrapping swellable polymers, inherent low density substances, porous excipients, hollow/porous particles inducing preparation techniques or sublimating agents. Therefore, this rev...
AMB Express
The limited therapeutic options associated with methicillin-resistant Staphylococcus aureus (MRSA... more The limited therapeutic options associated with methicillin-resistant Staphylococcus aureus (MRSA) necessitate search for innovative strategies particularly, use of natural extracts such as lyophilized royal jelly (LRJ) and garlic extract (GE). Therefore, out study aimed to formulate emulgels containing different concentrations of both LRJ and GE and to evaluate their activities using a murine model infected with MRSA clinical isolate. Four plain emulgel formulas were prepared by mixing stearic acid/yellow soft paraffin-based O/W emulsion formulae based on Carbopol 940, Na alginate, Na carboxymethylcellulose or Hydroxypropyl methyl cellulose E4. Sodium alginate-based emulgel was selected for preparation of four medicated emulgel formulations combining LRJ and GE at four different concentrations. The selected medicated emulgels were used for the in vivo studies. The emulgel formulated with Na alginate and HPMC (MF3) exhibited optimum smooth homogeneous consistency, neutral pH, accept...
Journal of Pharmacy & Pharmaceutical Sciences, 2015
Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric re... more Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric residence and a drug release independent of patient related variables. It is usually useful in improving local gastric treatment as well as overcoming drug-related problems .i.e. drugs having narrow absorption window, short half-life or low intestinal solubility. Buoyancy is considered one of the most promising approaches for gastro-retention of dosage forms. Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach causing an increase in gastric residence time. The buoyancy of these systems is attained by the aid of substances responsible to generate the low density. Various agents with different mechanisms were adopted either gas-generating agents, air entrapping swellable polymers, inherent low density substances, porous excipients, hollow/porous particles inducing preparation techniques or sublimating agents. Therefore, this rev...
Despite the inherent ability of bone for self-repair, this spontaneous healing capability in some... more Despite the inherent ability of bone for self-repair, this spontaneous healing capability in some bone disorders is not sufficient. Diseases as osteomyelitis, osteosarcoma, and osteoporosis, usually demand medical and/or surgical interventions to enhance tissue regeneration, control infection or to handle the clinical condition. Osteomyelitis (OM) is a bone infection disease, where Staphylococcus (S.) aureus is the main causative microorganism. OM is characterized by elevated rates of relapse and mortality. Coupling local osseous delivery of antibacterial agents with bioactive agents capable of bone regeneration was intensely studied for the treatment of OM, proving their effectiveness. Bioceramics are widely investigated due to their osteoconductive and osteointegration nature. Among these are calcium phosphates (CP), which are distinguished by a similar structure to that of bones and diverse resorption rates. CP is applied in the bone regeneration field, either solely or as compos...
International Journal of Pharmaceutics
International Journal of Pharmaceutics
International Journal of Pharmaceutics
Molecular Pharmaceutics
Intra-articular (IA) injection of thermo-responsive hydrogels coupled with microparticles (MPs) p... more Intra-articular (IA) injection of thermo-responsive hydrogels coupled with microparticles (MPs) possess the benefit of sustaining the anti-inflammatory drug effect within the joint cavity for rheumatoid arthritis treatment. Star-shaped thermo-responsive poly(polyethylene glycol) methacrylate [Poly(PEGMA)] copolymers were synthesized using free radical polymerization technique and fully characterized. Triamcinolone acetonide (TA)-loaded PLA/mPEG-PDL MPs, previously optimized, were integrated into the synthesized copolymer solutions at various concentrations, and tested for their gelation temperatures. The MPs-in-hydrogel formulations were characterized using scanning electron microscope (SEM), viscosity measurements, ex-vivo bio-adhesion and in-vitro release studies. The anti-inflammatory effect of integrated systems was assessed in adjuvant-induced mono-arthritic rat knee joints, and compared to Kenacort® and TA-loaded MPs. Two copolymers were successfully synthesized; G-1 = poly(PEGMA188-ME-co-PEGMA475-ME) and G-2 = poly(PEGMA246-EE-co-PEGMA475-ME). Using tube inversion technique, the gel formation was found dependent on copolymer concentration. An irreversible aggregation was obtained at copolymer concentrations ≤ 10% (w/v), while a gel was formed at 20 and 30% (w/v) of both copolymers upon increasing temperature. The MP-hydrogel formulations were optimized at 20 and 30% (w/v) of G-1 and G-2 with gelation temperatures of 33 and 37 °C, respectively. SEM images revealed the porous microstructures of hydrogels and their adsorption on MP surfaces. The integrated formulae showed pseudoplastic behaviours, while bio-adhesion study confirmed their bio-adhesiveness on excised cartilage. In-vitro release study confirmed drug sustainment from MPs-hydrogels compared to MPs. In-vivo studies proved the superiority of MP-in-hydrogels in treatment of induced arthritis, relative to Kenacort® and MPs alone, suggesting the applicability of this integrated platform in IA drug delivery.
International Journal of Pharmaceutics
A nanoemulsion system was designed for Atorvastatin calcium (ATOR) transdermal delivery to overco... more A nanoemulsion system was designed for Atorvastatin calcium (ATOR) transdermal delivery to overcome its poor bioavailability of (30%) resulting from the extensive first-pass effect and dissolution rate-limited in vivo absorption. Pseudo ternary phase diagrams were developed, and various NE formulae were prepared using oleic acid (OA), Tween 80 as surfactant and PEG 400 as cosurfactant, ethanol and limonene as permeation enhancers (PEs). NEs were characterized for morphology, droplet size, zeta potential and in vitro release. The optimized formulae were assessed for ex vivo transdermal permeation and in vivo pharmacodynamic/ pharmacokinetic studies. Hypocholesterolemic effect after 7 days skin treatment was detected and compared to oral ATOR dispersion. Finally, blood plasma levels were measured for 24 hr for rats received the selected transdermal NE and transdermal drug in OA. The obtained results suggested the low potentiality of NE systems in transdermal delivery of lipophilic drugs, only the addition of PEs is driving factor for increasing drug flux through full thickness rat skin. In the optimized formula, the presence of ethanol and PEG 400 disrupts SC lipids exhibiting rapid ex vivo release profile compared to other NEs and to ATOR in OA. In contrast, the optimized NE achieved a prolonged plasma profile. Transdermal NE was significantly more efficient than oral administration in lowering cholesterol plasma level and in increasing ATOR bioavailability. In conclusion, data revealed no correlation between ex vivo and in vivo studies explained by the collapse of the follicles in ex vivo skin permeation study, leaving only the lipoidal pathway for NE to pass through, thus only NE components, neither nanosizing nor other reported mechanisms, are the main influencing factors. In vivo experiments suggested that o/w NE changed ATOR pathway to follicular delivery leading to accumulation of NE in follicles and consequently a prolonged plasma profile.
Journal of Controlled Release
Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) i... more Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co-polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [3] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL1700, which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications.
Scientia Pharmaceutica
Nanoemulsions (NEs) are colloidal dispersions of two immiscible liquids, oil and water, in which ... more Nanoemulsions (NEs) are colloidal dispersions of two immiscible liquids, oil and water, in which one is dispersed in the other with the aid of a surfactant/co-surfactant mixture, either forming oil-in-water (o/w) or water-in-oil (w/o) nanodroplets systems, with droplets 20–200 nm in size. NEs are easy to prepare and upscale, and they show high variability in their components. They have proven to be very viable, non-invasive, and cost-effective nanocarriers for the enhanced transdermal delivery of a wide range of active compounds that tend to metabolize heavily or suffer from undesirable side effects when taken orally. In addition, the anti-microbial and anti-viral properties of NE components, leading to preservative-free formulations, make NE a very attractive approach for transdermal drug delivery. This review focuses on how NEs mechanistically deliver both lipophilic and hydrophilic drugs through skin layers to reach the blood stream, exerting the desired therapeutic effect. It hi...
Drug Development and Industrial Pharmacy
Abstract Objective: The aim of this study is to evaluate the use of PEG/glycerides of different H... more Abstract Objective: The aim of this study is to evaluate the use of PEG/glycerides of different HLB; oleoyl macrogol-6-glycerides (Labrafil® M 1944 CS) and caprylocaproylmacrogol-8-glycerides (Labrasol®), compared to Labrafac lipophile® as PEG-free glyceride in the preparation of nanostructured lipid carriers (NLCs). PEG/glycerides are suggested to perform a dual function; as the oily component, and as the PEG-containing substrate required for producing the PEGylated carriers without physical or chemical synthesis. Methods: Lipid nanocarriers were loaded with simvastatin (SV) as a promising anticancer drug. An optimization study of NLC fabrication variables was first conducted. The effect of lyophilization was investigated using cryoprotectants of various types and concentrations. The prepared NLCs were characterized in terms of particle size (PS), size distribution (PDI), zeta potential (ZP), drug entrapment, in vitro drug release, morphology and drug–excipient interactions. The influence of glycerides ± PEG on the cytotoxicity of SV was evaluated on MCF-7 breast cancer cells, in addition to the cellular uptake of fluorescent blank NLCs. Results: The alteration between different oil types had a significant impact on PS, ZP and drug release. Both sucrose and trehalose showed the lowest increase in PS and PDI of the reconstituted lyophilized NLCs. The in vitro cytotoxicity and cellular uptake studies indicated that SV showed the highest antitumor effect on MCF-7 cancer cells when loaded into Labrasol® NLCs demonstrating a high cellular uptake as well. Conclusion: The study confirms the applicability of PEG/glycerides in the development of NLCs. Encapsulating SV in Labrasol®-containing NLC could enhance the antitumor effect of the drug.
International Journal of Pharmaceutics, 2017
The active tumor targeting ligands, hyaluronic acid (HA) and human serum albumin (HSA), are consi... more The active tumor targeting ligands, hyaluronic acid (HA) and human serum albumin (HSA), are considered promising targeting moieties of drug carriers for cancer therapy. The chitosan nanoparticles loaded with methotrexate (MTX-CsNPs) were employed as the core for subsequent coating process. HA and HSA coating solutions were used at different concentrations. The effect of different HA Mw (1000, 360, 10kDa) was also investigated. The coated MTX-CsNPs was characterized proving the success of surface functionalization. The antitumor activity of the prepared MTX-CsNPs was evaluated on MCF-7 breast cancer cell lines. Results showed that both 360 and 10kDa HA allowed for successful HA adsorption, while its Mw and concentration determined negative charge density. HSA coating was accompanied by a slight increase in nanoparticles (NPs) size and a final positive surface charge. The in vitro cytotoxicity proved that HA and HSA coated MTX-CsNPs improved the antitumor activity compared to uncoated NPs and free drug.
Journal of Pharmacy and Pharmacology, 2017
Objectives Exploring the use of statins as anticancer agents and exploiting different drug delive... more Objectives Exploring the use of statins as anticancer agents and exploiting different drug delivery systems in targeting these molecules to cancerous sites. Literature review was performed to investigate the use of statins in cancer treatment in one hand, and the different pharmaceutical approaches to deliver and target these drugs to their site of action. Key findings Statins were used for decades as antihypercholestrolemic drugs but recently have been proven potential for broad anticancer activities. The incorporation of statins in nanoparticulate drug delivery systems not only augmented the cytotoxicity of statins but also overcame the resistance of cancerous cells against the traditional chemotherapeutic agents. Statins-loaded nanoparticles could be easily tampered to target the cancerous cells and consequently minimal drug amount could be utilized. Summary This review reconnoitered the different endeavors to incorporate statins in various nanoparticles and summarized the succes...
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Papers by Rania Aziz Ishak