Hamdy Abdelkader

Design and Evaluation of Controlled-Release Niosomes and Discomes for Naltrexone Hydrochloride Ocular Delivery

This study aimed at preparing and evaluating Span 60-based niosomes for ocular delivery of naltrexone hydrochloride (NTX). Selected charged lipids [dicetyl phosphate (DCP) and stearyl amine (STA)] and surfactants [poly-24-oxyethylene cholesteryl ether (C24) and sodium cholate (CH)] were investigated as bilayer membrane additives and prepared using four different methods. A 5-fold increase in NTX entrapment efficiency (EE%) was achieved with 2%-5% mol/mol additives. Differential scanning calorimetry thermograms revealed that the additives completely abolished gel/liquid transition suggesting that the bilayer membranes could accommodate the additives. The volume diameters D (4, 3) of the prepared niosomes were significantly [p < 0.05, analysis of variance (ANOVA)] dependent on the additive used. D (4,3) values of F-C24 and F-CH were 22.41 ± 1.40 and 5.37 ± 1.40 μ m, respectively. F-S60, F-DCP, and F-CH shapes were typical spherical, whereas F-C24 was oval giant niosomes (discomes). In vitro drug release parameters showed that the prepared niosomes significantly (p < 0.01, ANOVA) controlled NTX release rate and extent. Ex vivo transcorneal permeation studies conducted using excised cow corneas showed that niosomes were capable of controlling NTX permeation and enhance its corneal permeability. The prepared niosomal formulations were found practically nonirritant when applied onto the surface of a 10-day-old hens chorioallantoic membrane.

Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations

Abstract Non-ionic surfactant vesicles, simply known as niosomes are synthetic vesicles with potential technological applications. Niosomes have the same potential advantages of phospholipid vesicles (liposomes) of being able to accommodate both water soluble and lipid soluble drug molecules control their release and as such serve as versatile drug delivery devices of numerous applications. Additionally, niosomes can be considered as more economically, chemically, and occasionally physically stable alternatives to liposomes. Niosomes can be fabricated using simple methods of preparations and from widely used surfactants in pharmaceutical technology. Many reports have discussed niosomes in terms of physicochemical properties and their applications as drug delivery systems. In this report, a brief and simplified summary of different theories of self-assembly will be given. Furthermore manufacturing methods, physical characterization techniques, bilayer membrane additives, unconventional niosomes (discomes, proniosomes, elastic and polyhedral niosomes), their recent applications as drug delivery systems, limitations and directions for future research will be discussed.

Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.

New therapeutic approaches in the treatment of diabetic keratopathy: a review.

The cornea is densely innervated, and the integrity of these nerve fibres is critical in maintaining the refractive and protective functions of the cornea. Many ocular and systemic diseases can adversely affect corneal sensory nerves and consequently impair their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatments regimens are often ineffective. Over the past three decades, the role of growth factors in maintaining the normal structure and function of the cornea, and in corneal epithelial healing, has become increasingly evident. Many preclinical and clinical trials have shown that growth factors and cytokines can significantly enhance epithelialization (epithelial proliferation and migration) and consequently accelerate wound healing. More recently, local/topical administration of insulin, naltrexone (opioid antagonist) and nicergoline (ergoline derivatives) were found to improve, and significantly increase, the corneal wound healing rate. This report reviews the major attributes of these growth factors and therapeutic agents that may be used in ameliorating impaired corneal wound healing, and presents a perspective on the potential clinical use of these agents as a new generation of ophthalmic pharmaceuticals for the treatment of diabetic keratopathy.The cornea is densely innervated, and the integrity of these nerve fibres is critical in maintaining the refractive and protective functions of the cornea. Many ocular and systemic diseases can adversely affect corneal sensory nerves and consequently impair their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatments regimens are often ineffective. Over the past three decades, the role of growth factors in maintaining the normal structure and function of the cornea, and in corneal epithelial healing, has become increasingly evident. Many preclinical and clinical trials have shown that growth factors and cytokines can significantly enhance epithelialization (epithelial proliferation and migration) and consequently accelerate wound healing. More recently, local/topical administration of insulin, naltrexone (opioid antagonist) and nicergoline (ergoline derivatives) were found to improve, and significantly increase, the corneal wound healing rate. This report reviews the major attributes of these growth factors and therapeutic agents that may be used in ameliorating impaired corneal wound healing, and presents a perspective on the potential clinical use of these agents as a new generation of ophthalmic pharmaceuticals for the treatment of diabetic keratopathy.

Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen's egg chorioallantoic membrane and excised bovine cornea models.

This study aimed at combining the hens egg test-chorioallantoic membrane (HET-CAM), bovine corneal opacity and permeability (BCOP) test and histological examination of excised corneas to evaluate the conjunctival and corneal toxicity of niosomes and their ingredients. Various surfactant/lipid combinations and concentrations (1-10%, w/v) were investigated for the ocular delivery of an ambitious drug (naltrexone hydrochloride) for treatment of diabetic keratopathy. Four niosomal formulations were investigated and found to be non irritant to the 10 days old HET-CAMs (an acceptable conjunctival model). Only one of the tested ingredients (sodium cholate - CH) showed moderate irritation, however such an effect was diminished when incorporated into niosomes. Corneal opacity and fluorescein permeability scores for the test substances correlated well with the HET-CAM test results. Corneal erosion and stromal thickness were found to be in agreement with the HET-CAM and BCOP results, which discriminated well between moderately and mildly irritant test substances. Corneal histological examination revealed toxicity signs included epithelial erosion, stromal condensation and stromal vacuolisation, which allowed better discrimination between strong and moderate irritants. It is concluded that the prepared niosomes possess good ocular tolerability and minimal ocular tissue irritation. They can be further investigated as ocular delivery systems using appropriate animal models.

Niosomes and discomes for ocular delivery of naltrexone hydrochloride: morphological, rheological, spreading properties and photo-protective effects.

Naltrexone hydrochloride (NTX) is a promising treatment for corneal disorders linked to diabetes mellitus (diabetic keratopathy). However, NTX has a major stability problem due to autoxidation, which is likely to hinder its formulation as eye drops for treatment of diabetic keratopathy. In this study, in-house developed NTX non-ionic surfactant vesicles (niosomes and discomes) were evaluated for their spreading, rheological properties and their ability to impede the inevitable autoxidation of NTX in aqueous solutions. The measured contact angles and spreading coefficients for niosomes reflected significantly (P<0.05) better wetting and spreading abilities than the aqueous vehicle. The prepared niosomes were significantly more viscous (P<0.05) than the aqueous solution. The lipid content, size and composition of niosomes are the main factors affecting the viscosity of niosomal dispersions. Exposure of NTX solution to artificial daylight illumination (10,000 lux) can produce extensive degradation of NTX due to oxidation. The prepared formulations were able to significantly (P<0.05) protect the encapsulated NTX from the photo-induced oxidation compared with free NTX solutions. The investigated niosomes lend themselves as a potential ocular delivery modality for NTX.

Controlled and Continuous Release Ocular Drug Delivery Systems: Pros and Cons

Topical ocular drug administration is the most preferred route for treating conditions affecting the surface of the eye as well as anterior segment diseases; this is mainly due to the rapid and localised drug action and patient acceptability. However, the ocular bioavailability is typically less than 5% from conventional ophthalmic dosage forms such as eye drops. This is mainly due to the unique anatomical and physiological features of the eye. One of the effective pharmaceutical approaches is to provide a controlled and continuous drug release to the surface of the eye to compensate drug loss by nasolacrimal drainage and non-productive absorption of the topically applied drug. This review provides a critical appraisal (advantages and drawbacks) of the different drug delivery strategies that provides controlled and continuous drug supply to the surface of the eye; it covers research conducted over the past three decades.

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation, characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed by solid state analyses. Complete drug amorphiztion was attained at 1∶3 (wt/wt) drug: PVP, 25% (wt/wt) ND in PVP. According to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris at ∼129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution efficiency, respectively. In vivo experiments in mice demonstrated that administration of 60 mg/kg of drug coprecipitated with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power, dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing a reduced-dose, fast-release solid oral dosage form of nimesulide.

Preparation, characterization and evaluation of novel elastic nano-sized niosomes (ethoniosomes) for ocular delivery of prednisolone

Abstract Niosomes embodying ethanol and minimum amount of cholesterol (ethoniosomes) could be promising ocular delivery systems for water soluble and insoluble drugs. This manuscript reports on novel nano-sized elastic niosomes (ethoniosomes) composed of Span 60: cholesterol (7:3 mol/mol) and ethanol, for ocular delivery of prednisolone acetate (Pred A) and prednisolone sodium phosphate (Pred P). These ethoniosomes were prepared with the thin film hydration (TFH) and ethanol injection (EI) methods, characterized for percentage entrapment efficiency (% EE), size, zeta potential, morphology, elasticity, in vitro release and physical stability. Ocular irritation, bioavailability and anti-inflammatory effects were evaluated and compared with the conventional suspension and solution eye drops. The prepared ethoniosomal vesicles (EV) had a Z-average diameter of 267 nm, zeta potential of approximately −40 mV and % change in size after extrusion of 4%. They were physically stable for at least 2 months at 4 °C. The prepared EV showed good ocular tolerability using the modified Draize’s test and the estimated relative ocular bioavailability for Pred A EV and Pred P EV was 1.54 and 1.75 times greater than that for the suspension and solution eye drops, respectively. The time required for complete healing from the clove oil-induced severe ocular inflammation was reduced to half with Pred A and Pred P EV. More interestingly, the intraocular pressure (IOP) elevation side effect recorded for Pred A and Pred P EV was significantly less than that for the conventional suspension and solution eye drops.

Age-related cataract and drug therapy: opportunities and challenges for topical antioxidant delivery to the lens

The search for anticataract drugs has been continuing for decades; some treatments no longer exist but antioxidants are still of much interest.