Development of folic acid-loaded nanostructured lipid carriers for topical delivery: preparation, characterisation and ex vivo investigation.

The present work is designed to achieve efficient localised skin delivery of folic acid (FA)-loaded nanostructured lipid carriers (NLCs) to infer efficient treatment of skin photoageing conditions induced via excessive exposure to ultraviolet (UV) radiation. FA NLCs were prepared by high-speed homogenisation followed by ultrasonication. The obtained NLCs revealed high encapsulation efficiencies (89.42-99.26%) with nanometric particle sizes (27.06-85.36 nm) of monodisperse distribution (PDI = 0.137-0.442), zeta potential values >|27| mV, pseudoplastic rheological behaviour, good spreadability (2.25-3.30 cm) and promoted occlusive properties throughout 48 h. Optimised NLC formulations appeared as sphere-shaped particles using transmission electron microscopy, showed improved photostability of FA and prolonged in vitro release profile best fitted to Higuchi diffusion model. Ex vivo permeation and deposition of FA, employing Wistar rat skins, depicted enhanced permeability and existence of FA in skin layers after 6 h. Based on the obtained results, FA-loaded NLC formulations demonstrate a promising modality for anti-photoageing therapy.

Application of liquisolid technology for promoting the renoprotective efficacy of walnut extracts in chronic renal failure rat model.

Chronic renal failure (CRF) is among the major health problems that could lead to increased morbidity and mortality among population. 'Nutraceuticals' is an emerging field for natural agents from plant foods that could reduce the progression of such disease. Many newly developed drugs are having bioavailability problems owing to their water insolubility. Liquisolid technique is one of the promising technological approaches to increase solubility and hence, drug absorption. The aim of the present research is to prepare and evaluate the renoprotective effect of the walnut extracts liquisolid formulations in CRF rat model. Saturation solubility study claimed PEG 400 and Tween 20 as good solubilizers for walnut extracts, thus chosen for preparation. The angle of slide was determined for the carrier; microcrystalline cellulose and coating material; silicon dioxide and liquid load factor was evaluated. Eight liquisolid systems were prepared employing 25% and 50% of liquid medication. Their flow and compressibility parameters showed good properties. Dissolution study was more in favor of formulations prepared using PEG 400. Of these, formulation F8 comprising carrier/coat ratio (10:1) and 50% liquid medication, showing superior dissolution properties was selected to perform stability and in-vivo evaluations. Two CRF induced rat groups received F8 at two oral doses (50 and 100 mg/kg). Biochemical and nutritional parameters were compared with both normal and CRF control rats. Results showed improvement of renal function, oxidative stress, antioxidant and inflammatory biomarkers as well as increased appetite and body weight gain on administration of both doses of walnut liquisolid formulation, F8.

Transdermal fennel essential oil nanoemulsions with promising hepatic dysfunction healing effect: in vitro and in vivo study.

Fennel (Foeniculum vulgare Mill.) is a member of family Apiaceae. Trans-anethole, the major component of Fennel essential oil (FEO), possesses antioxidant and hepatoprotective effects. Transdermal nanoemulsions (NEs) are advanced colloidal systems for systemic and controlled drug delivery through the stratum corneum barrier. FEO NEs were prepared using the oil Lauroglycol™ 90, as it provides a larger NE existence zone than Captex® 300, in the constructed phase diagrams. Six systems were prepared using Tween20/propylene glycol (S/CoS) in the ratios 2:1 and 3:1 with oil to S/CoS mass ratios 1:9, 2:8 and 3:7. Physicochemical characterization revealed optimum properties regarding thermodynamic stability, droplet size and pH with a Newtonian flow pattern. In vitro permeation study in rat skin revealed the highest cumulative amount permeated (µg/cm2), flux and permeability coefficient values for F4 made up of 2% FEO, 4.67% Lauroglycol™ 90, 60% S/CoS in the ratio 3:1. Results of the in vivo hepatic dysfunction study in rats indicate promising significant amelioration of liver function reflected in ALT, AST, ALP, bilirubin, albumin, malondialdehyde and ammonia plasma levels. The results signify the promising approach of FEO NEs in achieving remedy of liver toxicity. The most promising effect is inherent to F4 which imparts a more positive effect than FEO.

Niosomal encapsulation of the antitubercular drug, pyrazinamide.

It is estimated that more than one-third of the world population is infected with Mycobacterium tuberculosis. Pyrazinamide (PZA) plays a unique role in shortening therapy because it kills a population of semilatent tubercle bacilli residing in an acidic environment. Niosomes are vesicles made up of non-ionic surfactant and exhibit behavior similar to liposomes in vivo. Preparation of PZA niosomes took place using different molar ratios of Span 60 and Span 85, with cholesterol (CH) i.e. Span: CH (1:1) and (4:2). Dicetyl phosphate and stearyl amine were used in preparation of negative and positively charged niosomes, respectively. Free PZA was separated by cooling centrifugation and estimated spectrophotometrically at 268.4 nm. Niosomes were characterized by electron microscopy and differential scanning calorimetry. The highest percentage PZA entrapped was obtained using Span 60 and the molar ratio (4:2:1) negatively charged niosomes. This was followed by the neutral PZA neutral (4:2) Span 60 niosomes. Biological evaluation of selected PZA niosomal formulations took place on guinea pigs infected with M. tuberculosis. The present work is an attempt to target maximum concentration of PZA to the affected site (lungs) and to exclude undesirable side effects and decrease toxicity. Macrophage targeting and overcoming drug resistance is our final goal.

Chitosan based Pickering emulsion as a promising approach for topical application of rutin in a solubilized form intended for wound healing: In vitro and in vivo study.

The aim of the present study is to formulate the hydrophobic drug rutin in a solubilized form, intended for wound healing, via its loading into a novel Pickering emulsion stabilized by self aggregated chitosan particles (SACP). Rutin-loaded Pickering emulsion formulae were prepared using a high speed homogenizer. They were characterized by drop test, optical microscopy, droplet size and zeta potential determination. The results revealed that SACP have a nano size and a contact angle of 42.47±1.19° that tend to stabilize O/W emulsion. The droplet size of all investigated formulations ranged between 5.8±1.1 and 18.7±3.4µm. The long term stability study revealed that formulae containing 20% and 30% oily phase were stable against coalescence, the droplet size was slightly increased with zeta potential ranged from -48.1±4.7 to -78.4±4.1mV, during the storage period up to 5 months, indicating good stability. The release of rutin was almost 100% within 24h. Treatment of the wounded skin tissue of the Albino rats with the selected formula, for ten days, revealed almost complete healing. Biochemical analysis for oxidative stress markers, hyaluronic acid and collagen type I in addition to histopathological study were performed. The results suggested that the sustained release of rutin in a solubilized form as well as the synergistic effect of other components of the prepared Pickering emulsion could have a potential wound healing effect.

Transdermal microemulsions of Boswellia carterii Bird: formulation, characterization and in vivo evaluation of anti-inflammatory activity.

CONTEXT: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East. OBJECTIVE: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy. MATERIALS AND METHODS: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-ß-boswellic acid (AKBA), at 210 nm. The bioactive fraction was incorporated in 6 MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity. RESULTS AND DISCUSSION: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam. CONCLUSIONS: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance.

Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-ß-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety.

CONTEXT: Tuberculosis (TB) is a worldwide health concern. In 2011, about 8.7 million new cases developed TB and 1.4 million people died from it. OBJECTIVE: Enhancement of ethambutol hydrochloride activity and safety in treatment of TB through niosomal encapsulation. MATERIALS AND METHODS: Niosomes were prepared by the thin-film hydration method. They were characterized, investigated for in vitro release, lung disposition and in vivo biological evaluation. RESULTS: Entrapment efficiency of ethambutol hydrochloride ranged from 12.20% to 25.81%. Zeta potential values inferred stability of neutral and negatively charged formulations. In vitro release was biphasic. Lung targeting was increased by niosomal encapsulation. Biological evaluation revealed superiority of niosomal ethambutol hydrochloride over the free drug. DISCUSSION: Neutral and negatively charged niosomal vesicles are dispersed homogenously unlike positively charged vesicles. Niosomal encapsulation results in controlled drug release. Niosomal formulations targeted more drugs to mice lungs for a prolonged period of time resulting in: decreased root-specific lung weight, bacterial counts in lung homogenates and optimizing pathological effect on guinea pigs lungs, livers and spleens. CONCLUSION: Encapsulation of ethambutol hydrochloride in niosomal formulations for the treatment of TB provides higher efficacy and safety compared with the free drug.