Topical caffeine-loaded nanostructured lipid carriers for enhanced treatment of cellulite: A 32 full factorial design optimization and in vivo evaluation in rats.

The goal of this study was the development and evaluation of semisolid caffeine (CAF) loaded nanostructured lipid carriers (NLCs) for topical treatment of cellulite. CAF-loaded NLC formulations were prepared via high-speed homogenization followed by ultrasonication. A 32 full factorial design was employed for formulation optimization. The total lipid content (%) and the liquid lipid content per total lipids (%) were chosen as factors, whereas particle size (PS), polydispersity index (PDI), zeta potential (|ZP|) and viscosity (VIS) were selected as responses. The design suggested CAF-NLC3 as the optimum formulation consisting of a total lipid content of 15% w/w (palmitic acid and soft paraffin/isopropyl myristate, 7:3 w/w) and a surfactant content of 10% w/w (Tween 80/lecithin, 8:1.2 w/w). CAF-NLC3 revealed PS, PDI, ZP, VIS and CAF content values of 318.8 nm, 0.253, -41.1 mV, 18.0 Pa.s and 97.57%, respectively. It showed a pseudoplastic rheological behavior, acceptable pH value (5.25), good spreadability (1.12 mm2/g) and spherical shape employing transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction demonstrated the amorphization of CAF in CAF-NLC3. CAF-NLC3 remained stable for 3 months at room and refrigeration conditions. A single topical application of CAF-NLC3 on shaved abdominal skins of Wistar rats revealed enhanced skin retention of CAF by 2-fold and 1.4-fold after 4 h when compared with plain CAF gel (CAF-P) and marketed CAF gel (CAF-M), respectively. Furthermore, CAF-NLC3 exhibited a superior anti-cellulite activity in comparison with CAF-P and CAF-M through elevating extracellular matrix components (collagen 1, elastin and hyaluronic acid) and stimulating the brown adipose tissue thermogenesis via up-regulating UCP1 and PPAR-γ expression. In addition, CAF-NLC3 prominently increased lipolysis through HSL activity and decreased pro-inflammatory cytokines such as ICAM-1 and VCAM-1 after 30 days of treatment on a high fat diet-induced cellulite rat model. These findings were further confirmed by histopathological examination supported by morphometric analysis. Therefore, incorporation of CAF in a semisolid NLC formulation would be a promising cosmetic approach for the topical treatment of cellulite.

Vitamin D3-Loaded Nanoemulsions as a Potential Drug Delivery System for Autistic Children: Formulation Development, Safety, and Pharmacokinetic Studies.

The aim of the current study is the development of a vitamin D3 (VD3)-loaded nanoemulsion (NE) formulation to improve VD3 oral bioavailability for management of vitamin D inadequacy in autistic children. Eight NE formulations were prepared by high-speed homogenization followed by ultrasonication. Four vegetable oils were employed along with two concentrations of Span 20 as the emulsifier. Glycerol, fructose, and mango flavor were included as viscosity modifier, sweetening, and flavoring agents, respectively. The prepared VD3-loaded NE formulations exhibited high drug content (> 98%), droplet size (DS) ranging from 61.15 to 129.8 nm with narrow size distribution, zeta potential values between - 9.83 and - 19.22 mV, and acceptable pH values (4.59-5.89). Storage stability showed that NE formulations underwent coalescence and phase separation during 6 months at room temperature, whereas at refrigerated conditions, formulations showed slight creaming. The optimum formulation (VD3-NE6) revealed a non-significant DS growth at refrigerated conditions and spherical morphology under transmission electron microscopy. VD3-NE6 did not produce any toxic effects to rats treated orally for 3 months, where normal blood picture and kidney and liver functions were observed compared to control rats. Also, serum calcium, oxidative stress, and apoptosis biomarkers remained within normal levels, indicating the safety of the optimum formulation. Furthermore, evaluation of VD3-NE6 oral bioavailability depicted a significant increase in AUC0-72 and Cmax with decreased Tmax compared to plain VD3. The optimum formulation demonstrated improved stability, safety, and oral bioavailability indicating the potential for successful management of vitamin D deficiency in autistic children.

Chrysin-phospholipid complex-based solid dispersion for improved anti-aging and neuroprotective effects in mice.

The present study aimed to improve the neuroprotective effect of chrysin (CHR) by combining two formulation techniques, phospholipid (PL) complexation and solid dispersion (SD). CHR-phospholipid complex (CHR-PLC) was prepared through solvent evaporation. The molar ratio CHR/PL (1:3), which exhibited the highest complexation efficiency, was selected for the preparation of CHR-PLC loaded SD (CHR-PLC-SD) with 2-hydroxypropyl ß cyclodextrin (2-HPßCD) and polyvinylpyrrolidone 8000. CHR-PLC/2-HPßCD (1:2, w/w) displayed the highest aqueous solubility of CHR (5.86 times more than that of plain CHR). CHR-SD was also prepared using 2-HPßCD for comparison. The in vitro dissolution of CHR-PLC-SD4 revealed an enhancement in the dissolution rate over CHR-PLC (1:3), CHR-SD, and plain CHR by six times. The optimum formulations and plain CHR were evaluated for their neuroprotective effect on brain aging induced by D-galactose in mice. The results demonstrated a behavioral activity elevation, an increase of AMPK, LKB1, and PGC1α brain contents as well as a reduction of AGEs, GFAP, NT-3, TNF-α, and NF-κß brain contents when compared with those of the D-galactose control group. Thus, the developed formulations stimulated neurogenesis and mitochondrial biogenesis as well as suppressed neuroinflammation and neurodegeneration. The order of activity was as follows: CHR-PLC-SD4 > CHR-PLC (1:3) > CHR-SD > plain CHR.

Chitosan/ß-glycerophosphate in situ forming thermo-sensitive hydrogel for improved ocular delivery of moxifloxacin hydrochloride.

The aim of the current work is to develop a thermo-sensitive hydrogel system of moxifloxacin hydrochloride (MOX) for improved ocular delivery. Fifteen formulations were prepared at different concentrations of ß-glycerophosphate disodium salt (ß-GP) 12-20% (w/v) and chitosan (CS) 1.7-1.9% (w/v). The optimized MOX loaded thermo-sensitive hydrogel system (F8), consisting of CS (1.8%, w/v) and ß-GP (16%, w/v), showed optimum gelation temperature (35 °C) and gelation time (2 min), thus was selected for further investigations. It showed a significant decrease (p < 0.05) in the zeta potential value compared to CS solution with a favorable pH value (7.1) and confirmed thermoreversible behavior. MOX loaded F8 displayed a porous structure under scanning electron microscopy. Rheological investigation of MOX loaded F8 revealed the presence of a strong hydrogel network with high elasticity along with a small loss factor of 0.08 indicating a great ease of gel formation. The release of MOX from F8 was found to be governed by a combined mechanism of diffusion and relaxation. Biological assessment of two concentrations of MOX loaded F8 (0.25 and 0.5%) was conducted using healthy and infected male albino New Zealand rabbits, where an improved and prolonged antibacterial activity against Staphylococcus aureus compared to plain MOX (0.5%), marketed MOX eye drops (0.5%), was shown. Moreover, histopathological examination of ocular tissues confirmed the antibacterial efficacy of the optimized formulation eight days post topical therapy. Consequently, the developed CS/ß-GP thermo-sensitive hydrogel system (F8) reveals a promising potential for enhancing the ocular delivery of MOX for treatment of bacterial infections.

Improved hepatoprotective activity of Beta vulgaris L. leaf extract loaded self-nanoemulsifying drug delivery system (SNEDDS): in vitro and in vivo evaluation.

OBJECTIVE: Beta vulgaris L. (beetroot) is a vegetable plant rich in phytochemical compounds such as phenolic acids, carotenoids and flavonoids. The objective of the current study is the development and optimization of self-nanoemulsifying drug delivery systems (SNEDDSs) to enhance the hepatoprotective activity of beet leaf (BL) extract. METHODS: Total flavonoids content was estimated in the BL extract and its solubility was evaluated in various vehicles to select proper component combinations. Pseudo-ternary phase diagrams were constructed employing olive, linseed, castor and sesame oils (oil phase), Tween® 20 (Tw20) and Tween® 80 (Tw80) (surfactants (SAs)) as well as dimethyl sulfoxide (DMSO) and propylene glycol (PG) (co-surfactants (Co-SAs)). Optimization of formulations from the phase diagrams took place through testing their thermodynamic stability, dispersibility and robustness to dilution. RESULTS: Four optimized BL-SNEDDS formulations, comprising linseed oil or olive oil, Tw80 and DMSO at two SA/Co-SA ratios (2:1 or 3:1) were chosen. They exhibited high cloud point and percentage transmittance values with spherical morphology of mean droplet sizes ranging from 14.67 to 16.06 nm and monodisperse distribution with negatively charged zeta potential < -9.51 mV. The in vitro release profiles of the optimized formulations in pH 1.2 and 6.8 were nearly similar, with a non-Fickian release mechanism. In vivo evaluation of BL-SNEDDSs hepatoprotective activity in a thioacetamide-induced hepatotoxicity rat model depicted promoted liver functions, inflammatory markers and histopathological findings, most prominently in the group treated by F7. CONCLUSION: The results indicate that SNEDDS, as a nanocarrier system, has potential to improve the hepatoprotective activity of the BL extract.

Hydrophobic ion pair loaded self-emulsifying drug delivery system (SEDDS): A novel oral drug delivery approach of cromolyn sodium for management of bronchial asthma.

The aim of the present study is to develop a self-emulsifying drug delivery system (SEDDS) for the hydrophobic ion pair (HIP) complex of cromolyn sodium (CS), in order to enhance its intestinal absorption and biological activity. Two ion pairing agents (IPAs) were investigated: hexadecyl pyridininum chloride (HPC) and myristyl trimethyl ammonium bromide (MTAB). The optimum binding efficiency for complexation between investigated IPAs and CS was observed at a molar ratio of 1.5:1, where CS binding efficiency was found to be 76.10 ± 2.12 and 91.37 ± 1.73% for MTAB and HPC, respectively. The two prepared complexes exhibited a significant increase in partition coefficient indicating increased lipophilicity. The optimized CS-HIP complex was incorporated into SEDDS formulations. SEDDS formulations F2 (40% oleic acid, 40% BrijTM98, 20% propylene glycol) and F3 (25% oleic acid, 50% BrijTM98, 25% propylene glycol) exhibited nanometric droplet diameters with monodisperse distribution and nearly neutral zeta potential values. Ex vivo intestinal permeation study, using the non-everted gut sac technique, revealed a significantly higher cumulative amount of permeated drug, after 2 h, for F2 and F3 (53.836 and 77.617 µg/cm2, respectively) compared to 8.649 µg/cm2 for plain CS solution. The in vivo evaluation of plain CS solution compared to F2 and F3 was conducted in an ovalbumin sensitization-induced bronchial asthma rat model. Lung function parameters (tidal volume and peak expiratory flow), biochemical parameters (interleukin-5, immunoglobulin-E, myeloperoxidase and airway remodelling parameters) were assessed in addition to histopathological examination. The results indicated the superiority of F3 followed by F2 compared to plain CS solution for prophylaxis of bronchial asthma in rats.

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.

Topical nanostructured lipid carriers/inorganic sunscreen combination for alleviation of all-trans retinoic acid-induced photosensitivity: Box-Behnken design optimization, in vitro and in vivo evaluation.

All-trans retinoic acid is a natural retinoid and the physiologically active metabolite of vitamin A. The aim of the present study is to develop and optimize a nanostructured lipid carrier formulation to enhance the photostability of all-trans retinoic acid and alleviate its skin photosensitivity. Box-Behnken design was used for optimizing dependent variables such as particle size, zeta potential and viscosity. The total lipid (%), liquid lipid (%) and total surfactant (%) were selected as independent variables. The optimized formulation was characterized by particle size of 151 nm, zeta potential of -31 mV and viscosity of 2064 cps. In vitro photoprotection effect of the optimized formulation containing different types and concentrations of inorganic sunscreens was evaluated employing Transpore® tape assay. Sun protection factor and other spectroscopic indices revealed that 6% titanium dioxide was the best choice to be combined with the optimized formulation. After 6 h of ultraviolet A exposure, the optimized formulation and the optimized formulation combined with 6% titanium dioxide enhanced the photostability of all-trans retinoic acid by about 1.5 and 2 times, respectively, compared to its methanolic solution. In vivo photoprotection effect of the developed formulations was conducted on mice exposed to direct sun light for 4 days. Photographs of the mice's skin, biochemical analysis of the pro-inflammatory cytokines in the skin as well as histopathological examination, depicted that the optimized formulation promoted an obvious alleviation of the all-trans retinoic acid-induced photosensitivity, which was further potentiated by the addition of 6% titanium dioxide, compared to the marketed product.

Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: In vitro and in vivo evaluation.

The current study aimed to develop an effective transdermal nanovesicular carrier of diflunisal that provides enhanced delivery through the skin. Two types of nanovesicles, ethosomes and transfersomes, were investigated and compared to conventional liposomes. Ethosomes with variable ethanol contents (10, 30 and 50%) and transfersomes using different edge activators, including sodium deoxycholate, sodium cholate and sodium taurocholate, were prepared and characterized. The obtained vesicles revealed good entrapment efficiencies (46.73-65.99%), nanometric vesicle sizes (453.10-796.80 nm) and negative zeta potential values (-45.40 to -86.90 mV). Ethosomes with 30% ethanol and sodium deoxycholate-containing transfersomes were incorporated into hydrogels to evaluate their in vitro release and permeation patterns. Nanovesicular hydrogels exhibited more sustained diflunisal release than did corresponding dispersions. Compared to liposomal hydrogel, both carriers proved the superiority of diflunisal permeation and flux across the skin. Confocal laser scanning microscopy showed improved penetration of rhodamine-loaded nanovesicles through skin layers with a wider distribution and higher fluorescence intensity. Compared to liposomes, selected nanovesicles exhibited remarkable antinociceptive and anti-inflammatory effects manifested by significant reduction in number of writhings and significantly higher inhibition of paw oedema. Hence, the developed nanovesicles could be considered promising carriers for transdermal delivery of diflunisal for pain and inflammation management.

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.

Nanotechnology Inspired Advanced Engineering Fundamentals for Optimizing Drug Delivery.

BACKGROUND: Drug toxicity and inefficacy are commonly experienced problems with drug therapy failure. To face these problems, extensive research work took place aiming to design new dosage forms for drug delivery especially nanoparticulate systems. These systems are designed to increase the quantity of the therapeutic molecule delivered to the desired site concurrently with reduced side effects. In order to achieve this objective, nanocarriers must principally display suitable drug vehiculization abilities and a controlled biological destiny of drug molecules. Only the intelligent design of the nanomedicine will accomplish these fundamentals. METHODS: The present review article is dedicated to the discussion of the important fundamentals to be considered in the fabrication of nanomedicines. These include the therapeutic agent, the imaging agent, the nanocarrier and the functionalization moieties. Special consideration is devoted to the explanation and compilation of highly potential fabrication approaches assisting how to control the in vivo destiny of the nanomedicine. Finally, some nanotechnology-based drug delivery systems, for the development of nanomedicine, are also discussed. RESULTS: The nanotechnology-based drug delivery systems show remarkable outcomes based on passive and active targeting as well as improvement of the drug pharmacodynamic and pharmacokinetic profiles. Multifunctional nanocarrier concept affords a revolutionary drug delivery approach for maximizing the efficacy, safety and monitoring the biological fate of the therapeutic molecule. CONCLUSION: Nanomedicines may enhance the efficacy of therapeutic molecules and reduce their toxic effects. Meanwhile, further research works are required to rightly optimize (and define) the effectiveness, nanotoxicity, in vivo destiny and feasibility of these nanomedicines which, from a preclinical standpoint, are actually promising.

Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG.

Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition.

The aim of the present study is to enhance the skin penetration and deposition of 8-methoxypsoraln (8-MOP) via niosomal vesicles to increase its local efficacy and safety. 8-MOP niosomes were prepared by the thin film hydration method using Span 60 or Span 40 along with cholesterol at five different molar ratios. The obtained vesicles revealed high entrapment efficiencies (83.04-89.90%) with nanometric vesicle diameters (111.1-198.8nm) of monodisperse distribution (PDI=0.145-0.216), zeta potential values <-48.3mV and spherical morphology under transmission electron microscopy. Optimized niosomal formulations depicted a biphasic in vitro release pattern in phosphate buffer (pH 5.5)/ethanol (7:3v/v) and displayed good physical stability after storage for 6 months at room (20-25°C) and refrigeration (4-8°C) temperatures. The two optimized formulations were incorporated in 5% sodium carboxy methylcellulose based hydrogel matrix which showed optimum pH values (7.37-7.39), pseudoplastic with thixotropic rheological behavior and more retarded 8-MOP release, by 23.82 and 14.89%, compared to niosomal vesicles after 24h. In vitro drug permeation and deposition studies, using rat skins, revealed promoted penetration and accumulation of 8-MOP after 8h. The skin penetration was further confirmed in vivo by confocal laser scanning microscopy, after 2h application period using rhodamine-loaded niosomal hydrogels compared to plain rhodamine hydrogel, as a florescence marker. Therefore, enhanced permeation and skin deposition of 8-MOP delivered by niosomes may help in improving the efficacy and safety of long-term treatment with 8-MOP.

Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect.

The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.

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.

Niosomes as a potential drug delivery system for increasing the efficacy and safety of nystatin.

Nonionic surfactant (NIS) vesicles (niosomes) formed from self-assembly of hydrated synthetic NIS monomers are capable of entrapping a variety of drugs and have been evaluated as an alternative to liposomes. Nystatin (NYS) is a polyene antifungal drug that has been used in the treatment of cutaneous, vaginal and oral fungal infections since the 1950s. The aim of this work is to encapsulate NYS in niosomes to obtain a safe and effective formula administered parenterally for neutropenic patients. NYS niosomes were prepared by the thin-film hydration method using Span 60 or Span 40 and cholesterol (CHOL). Stearylamine and dicetyl phosphate were added as the positive and negative charge-inducing agents (CIA), respectively. Two molar ratios were used, namely NIS/CHOL/CIA (1:1:0.1 and 2:1:0.25). Neutral and positively charged niosomes gave the highest encapsulation efficiencies. NYS niosomes were characterized using transmission electron microscopy, differential scanning calorimetry and dynamic light scattering. The release of neutral and negatively charged NYS niosomes was estimated, and it showed a slow sustained release profile. A 25-kGy γ-irradiation dose was sufficient to sterilize the investigated vesicles. NYS niosomes exerted less nephrotoxicity and hepatotoxicity in vivo, showed higher level of drug in vital organs and revealed pronounced efficacy in elimination of the fungal burden in experimental animals infected with Candida albicans compared with those treated with free NYS. Niosomal encapsulation thus provided means for parenteral administration of NYS, reducing its toxicity and making it a more active antifungal agent.