Dicetyl Phosphate Research Articles

Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma.

Despite its established anti-diabetic activity, Metformin hydrochloride (MET) has been repurposed for the management of hepatocellular carcinoma (HCC). Owing to MET high aqueous solubility and poor oral permeability, a novel nanoplatform is sought to overcome the current challenges of traditional formulations. In this study, we developed MET-bridged nanocochleates (MET-CO) using a direct bridging method followed by optimization and assessment using various in-vitro and in-vivo pharmacokinetic methods. The optimized nanocochleates MET-CODCP 19, containing dicetyl phosphate (DCP), displayed uniform snail-shaped nano-rolls measuring 136.41 ± 2.11nm with a PDI of 0.241 ± 0.005 and a highly negative ζ-potential of -61.93 ± 2.57 mV. With an impressive MET encochleation efficiency (> 75%), MET-CODCP 19 exhibited a controlled biphasic release profile, with minimal initial burst followed by prolonged release for 24h. Importantly, they showed significant MET permeation in both in-vitro Caco-2 and ex-vivo intestinal models compared to non-DCP containing formula or MET solution. The in-vivo oral bioavailability study demonstrated pronounced improvements in the pharmacokinetic parameters with a 5.5 relative bioavailability compared to MET solution. Notably, a significant reduction in IC50 values in HepG2 cells after 24h of treatment was observed. Furthermore, the optimized formulation showed a significant downregulation of anti-apoptotic and cancer stemness genes, with 12- and 2-fold lower expression compared to MET solution. These promising results highlight the efficacy of the novel MET-bridged nanocochleates as a stable nanoplatform for enhancing the oral bioavailability of MET and boosting its anticancer potential against HCC.

Variables Affecting the Preparation and Characterization of Axitinib as Oral Niosmoes

Axitinib is anticancer drug act on different solid tumors by inhibtion protein kinase enzyme which is responsible for support the tumors with blood demand. Due to its low solubility, it has low bioavailability when given orally also it is affected by liver metabolism. Axitinib formulated as non-ionic vesicles (niosomes) for the first time to study the effect of different variables on the in vitro behaviour of vesicles in a hope to improve drug oral bioavailability. Niosomal dispersion formulas were formulated by diverse techniques via multiple kinds of surface-active agent (tween also span), cholesterol and dicetyl phosphate then evaluated for visual appearance, efficiency of drug entrapment (EE%), size of the vesicles, poly dispersity index, zetapotential, viscosity, invitro drug release and study the vesicles morphology by FE-SEM. Many variables effect on EE% were studied such as effect of surfactant amount and type, effect of surfactant combination, impact of various ratios of cholesterol, impact of DCP in various amount , effect of preparation method and effect of sonication time. The results showed that the EE% between (50.97%-98.24%), the particle size was found within the range (64.5 nm - 530.79 nm), zeta potential which was between ( -16.6 to -31 mV), polydispersity index (PDI) <1 and viscosity between (584 – 889.6) centipoise. The niosomal dispersion F1 which contained 1:1 weight ratio (span60: cholesterol) was found with high EE% (96.5±0.16%), smallest particle size (64.5±0.5 nm), highest drug release (100%) of drug released at the end of 4 hours and FE-SEM photograph showed that niosomes were spherical with no aggregation and had a smooth surface. The results showed that thin film hydration method with sonication for four minutes was the best method for preparation of axitinib niosomes, the type and amount of surfactants used, cholesterol ratio, stabilizer and the time of sonication had a substantial effect on EE%, the size of the vesicles as well as drug release; which were investigated so as to optimize the niosomal dispersion of anti-tumour drug reaching to an optimum formula that may improve drug bioavailability. Key words: Axitinib, Anticancer, Vesicles, Surfactants, Invitro behaviour, Entrapment efficiency.

A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl2, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables—DMPC (X1, 70.58 mol%), cholesterol (X2, 22.54 mol%), and DCP (X3, 6.88 mol%)—and three response variables: encapsulation efficiency (Y1, 76.92%), released amount of free fatty acid at 2 h (Y2, 39.82%), and released amount of RVP at 6 h (Y3, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives.

Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 32 fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and −36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations.

Preparation and Evaluation of a Sustained Release Niosomal Dispersion Containing Niflumic Acid

Objective: This work aims to create and characterize niosomal dispersions for long-term delivery of the anti-inflammatory drug niflumic acid that may be adapted to give a localized effect, prevent gastrointestinal side effects and hepatic metabolism, leading to improve efficacy and patient compliance. Method: The thin film hydration technique was used to make niflumic acid-loaded niosomes. The effects of different concentrations of a non-ionic surfactant, cholesterol, dicetyl phosphate (DCP), sonication time and the effects of drug concentration on encapsulation efficiency were investigated in order to improve the process. Differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) were used to analyze the formulations. The niosomal dispersion formulations were evaluated for entrapment efficiency, in-vitro drug release, particle size, polydispersity index (pdI), zeta potential, pH and stability study. Results: The optimum niosomal preparation (F15) exhibited pH (7.2), size of the particles (1.04 μm), pdI (0.374), surface charge (-47.4) and efficiency of trapping (91.55%). It gave a rapid release in 15 minutes and increased sustainably over time until reach 96.9% within 24 hours. Conclusion: This research was successful in producing an optimal niosomal dispersion for niflumic acid using different surfactant/cholesterol ratios. The optimum formula provides a sustained release with the initial fast effect of niflumic acid and can be used with a topical dosage form to provide immediate relief that lasts for up to 24 h.

Pharmacokinetic Study of Abacavir Sulphate Loaded Niosomes and Proniosomes in Rats

The plasma pharmacokinetic study of abacavir sulphate was investigated after oral administration of free abacavir sulphate solution, freshly prepared niosomal and proniosomal abacavir sulphate dispersions. The abacavir sulphate loaded niosome vesicles were prepared by the thin-film hydration method and proniosomes were prepared by the slurry method using tween 60 as surfactant cholesterol as a membrane stabilizer and dicetyl phosphate as a negative charge inducer. Maltodextrin was used as a carrier in the proniosome formulations. The formulations were evaluated for various evaluation parameters such as drug-polymer interaction, phase identification analysis and in vivo pharmacokinetic study. The comparative pharmacokinetics of free, niosome encapsulated and proniosome encapsulated abacavir sulphate was evaluated in rats at a dose of 8.57 mg/kg of abacavir sulphate. The results of niosome and proniosome encapsulated abacavir sulphate showed a significant increase in bioavailability and prolonged release characteristics. Increased half-life of 3.40 h in the case of niosomes and 4.88 h in the case of proniosomes were observed. Based on the results, it can be concluded that niosomal and proniosomal formulation could be a promising delivery system for abacavir sulphate with improved oral bioavailability and prolonged drug release profiles.

Irinotecan Engineered Proniosomes: In vitro and In vivo Characterization

Objective: The focus of this research has been to improve efficacy, decrease tolerance and increase the irinotecan pharmacokinetic profile.
 Methods: Proniosomesformulated with various surfactants, cholesterol and dicetyl phosphate using the slurry method. A slurry process was used to prepare proniosomes with maltodextrin as the carrier by using surfactants span 20, span 60, tween 20 and tween 80.
 Results: The preparations were characterized in terms of shape and specific surface area, entrapment efficacy, in vitro release studies, in vivo tissue diffusion and stability testing. The proniosome surface was found to be smoother in nature showing thin and compact layer with skim milk powder. For formulation 2 (73.94±2.8%), the maximum entrapment efficacy was found.
 Conclusion: The formulation 3 obtained the desired maximum release profile within 24 hours (98.06%). The in vivo tissue distribution studies for the proniosomes reveal that the drug was preferentially targeted to liver followed by the alveolus and lymphatic system.Stability studies have indicated that the most acceptable condition for storage of the formulation 2 was 4o C. Proniosomes provide an acceptable method to the carrier for targeted therapy. These can be held at specific sites and can release the drug for a prolonged period of time.

Cochleate Formulation Enhances the Stability of Lansoprazole in Acidic Condition

Lansoprazole (LSP)‐loaded cochleates were developed using dimyristoyl phosphatidylcholine (DMPC) and cholesterol in the presence or absence of dicetyl phosphate (DCP). Cochleates containing DCP exhibited unique cylindrical morphologies, resulting in improved LSP loading and enhanced stability in an acidic environment. Thus, we suggest that the use of negatively charged components, such as DCP, is needed to formulate cochleates using a neutrally charged lipid such as DMPC.

Nanostructured lipid carriers for enhanced in vitro and in vivo schistosomicidal activity of praziquantel: effect of charge

WHO considers praziquantel (PZQ) as the drug of choice for treatment of Schistosoma mansoni infection but this requires high dose due to poor solubility and first pass metabolism. The aim of this work was to optimize nanostructured lipid carriers (NLCs) for enhanced PZQ oral delivery. The optimization involved testing the effect of surface charge of NLCs. NLCs comprised precirol ATO as solid lipid with oleic acid, Span 60 and Tween 80 as liquid components. Dicetyl phosphate and stearyl amine were the negative and positive charging agents, respectively. NLCs were prepared by microemulsification technique and were characterized. The schistosomicidal activity of PZQ loaded NLCs was monitored in vitro and in vivo using infected mice. PZQ showed high entrapment efficiency in all types of NLCs (ranged from 93.97 to 96.29%) with better PZQ loading in standard NLCs. This was clarified by thermal analysis which reflected displacement of PZQ by charging agents. In vitro schistosomicidal study revealed the superiority of PZQ loaded positively charged NLCs (LC50 and LC95 equal 0.147 and 0.193 µg/ml respectively) with traditional and negatively charged NLCs being inferior to simple PZQ solution after short incubation period. Scanning electron micrographs showed that PZQ loaded positively charged NLCs resulted in more intense ultrastructural changes in worms. The superiority of positively charged NLCs was confirmed by in vivo assessment as they showed better improvement in histopathological features of the liver of the infected mice compared with other formulations. The study introduced positively charged NLCs as promising carriers for oral delivery of PZQ.

Intelligently Thermoresponsive Ionic Liquid toward Molecular Firefighting and Thermal Energy Management.

Hydrocarbon-based phase change materials (PCMs) are accompanied by an inherent fire risk, which is hindering their further application especially in construction. Molecular-firefighting PCMs can be ideal and promising candidates to simultaneously ensure the highly efficient energy management and fire safety of PCMs. In this work, two novel phosphorus/nitrogen-containing ionic liquids ([DP][MI] and [DP][TEA]), composed of imidazole (MI) or triethylamine (TEA) cations and dicetyl phosphate (DP) anion, were synthesized for fire-proofing thermal energy management. The fire risk assessment confirmed that the extinguishing time of prepared [DP][MI] and [DP][TEA] was greatly shortened to 20 s and 3.5 min from 45 min for controlled sample, respectively. Moreover, the thermal enthalpy of [DP][MI] reached about 99.0 J g-1. In addition, [DP][MI] and [DP][TEA] achieved low supercooling extents of 2.2 and 4.4 °C, separately. Both molecular firefighting and efficient energy management were achieved for [DP][MI] and [DP][TEA]. As applied in wood-plastic composite which is ubiquitous in construction, [DP][TEA] endowed the composite with temperature-regulating capability of about 10 °C in hut test and remarkably suppressed fire hazard of the composite, displaying a potential application value.

Promising Antifungal Potential of Engineered Non-ionic Surfactant-Based Vesicles: In Vitro and In Vivo Studies.

Fungal keratitis (FK) is a corneal infection caused by different fungal species. It is treated by the topical application of natamycin (NAT). Nevertheless, this approach faces many limitations like toxic effects, frequent dosing, resistance, and patient discomfort. The present research reports the development of trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes by a modified thin-film hydration method. TMC was synthesized using a one-step carbodiimide method and characterized by 1H-NMR and degree of quaternization (53.74 ± 1.06%). NAT, cholesterol (CHOL), span 60 (Sp60), and dicetyl phosphate (DCP) were used to prepare niosomes which were incubated with TMC to obtain mucoadhesive cationic NAT loaded niosomes (MCNNs). MCNNs showed a spherical shape with 1031.12 ± 14.18nm size (PDI below 0.3) and 80.23 ± 5.28% entrapment efficiency. In vitro drug release studies showed gradual drug release from TMC coated niosomes as compared to the uncoated niosomes. MIC assay and disk diffusion assay revealed promising in vitro antifungal potential of MCNNs similar to the marketed formulation. For investigating in vivo performance, ocular retention and pharmacokinetics, ocular irritation, and ulcer healing studies were performed using the rabbit model. Mucoadhesive property and prolonged local drug release improved the safety and efficacy of NAT, suggesting that the developed niosomes could be an emerging system for effective treatment of fungal keratitis.

Design of Nanosystems for the Delivery of Quorum Sensing Inhibitors: A Preliminary Study.

Biofilm production is regulated by the Quorum Sensing system. Nowadays, Quorum Sensing represents an appealing target to design new compounds to increase antibiotics effects and avoid development of antibiotics multiresistance. In this research the use of liposomes to target two novel synthetic biofilm inhibitors is presented, focusing on a preformulation study to select a liposome composition for in vitro test. Five different liposome (LP) formulations, composed of phosphatidyl choline, cholesterol and charged surfactant (2:1:1, molar ratio) have been prepared by direct hydration and extrusion. As charged surfactants dicetyl phosphate didecyldimethylammonium chloride, di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride and stearylamine (SA) and have been used. Liposome charge, size and morphology were investigated by zeta potential, photon correlation spectroscopy, small angle x-ray spectroscopy and electron microscopy. LP-SA was selected for the loading of biofilm inhibitors and subjected to high performance liquid chromatography for entrapment capacity evaluation. LP-SA loaded inhibitors showed a higher diameter (223.6 nm) as compared to unloaded ones (205.7 nm) and a dose-dependent anti-biofilm effect mainly after 48 h of treatment, while free biofilm inhibitors loose activity. In conclusion, our data supported the use of liposomes as a strategy to enhance biofilm inhibitors effect.

Formulation, characterization, and evaluation of the anti-tumor activity of nanosized galangin loaded niosomes on chemically induced hepatocellular carcinoma in rats

Galangin (GAL) is a flavonoid with anti-tumor activity. However, its poor solubility results in low bioavailability thus hindering its clinical application. To overcome this challenge, we have prepared niosomal vesicles by reverse-phase evaporation technique using non-ionic surfactant (Span 20, Span 40, and Span 60) and cholesterol in diverse molar ratios with or without charge inducing agents including Dicetylphosphate (DCP) and Stearylamine (STR). The prepared niosomal formulations were evaluated for drug entrapment efficiency (DEE), Drug loading capacity (DL %), size, and cumulative % drug released. DEE ranged between 45.13 ± 0.35 and 77.69 ± 0.45%. DL% ranged from 9.02 ± 0.51 to 16.72 ± 0.39%. The vesicle size ranged between 173.7 ± 12.6 and 355.6 ± 17.9 nm. The optimized niosomal formulation; F8 (prepared from Span 60, cholesterol, and STR in a 1:1: 0.25 M ratios) was selected depending on its highest DEE, DL%, and suitable drug release profile. F8 was subjected to further investigations as FTIR, DSC analysis, zeta potential, scanning electron microscope, stability studies, and estimation of liver biomarkers. Histopathological examination and immunohistochemical assessment of Minichromosome maintenance 3 (MCM3) were done on extracted liver tissue. Significant improvement of liver biomarkers was observed with galangin loaded niosomes. Histopathological and immunohistochemical examination showed that GAL loaded niosomes exhibit marked decline in MCM3 immunostaining hepatocytes and neoplastic hepatic lesions with a small number of hepatic adenomas, thus GAL loaded niosomes are considered as a promising targeted system for improving anti-tumor activity against liver cancer.

Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug loaded niosomes with high energy probe sonication technique

The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.

IN VITRO IN VIVO EVALUATION OF NIOSOMAL FORMULATION OF FAMOTIDINE

Objective: The present study was aimed on formulation and evaluation of famotidine loaded niosomal formulation for in vitro and in vivo pharmacokinetic behaviour. Formulating it as niosomal formulation might be quite advantageous for prolonging the duration of pharmacological action and improved bioavailability.
 Methods: In the present study niosomal formulations were prepared by using most documented thin film hydration technique by using various grades of surfactants (span 20, 40, 60, 80) in varying ratios with cholesterol, negative charge inducer di cetyl phosphate (DCP) and drug famotidine. Suitable preformulation studies were conducted like identification of drug, excipient and drug compatibility study. The optimized drug loaded niosomes were characterized for size and morphology, polydispersity index, zeta potential, drug entrapment, in vitro release, in vivo study and stability study.
 Results: The results showed that the vesicles formed were spherical in shape, size ranging between 160.1 nm to 718.7 nm with zeta potential values indicating good stability and formulation containing span 60 (NMS7) showed the highest entrapment efficiency (73.234%). All the formulations showed prolonged release profile for more than 24 h with release kinetics better suited to zero order release pattern. In vivo study conducted on rabbits predicted a fourfold increase in pharmacokinetic parameter (area under curve)AUC and pharmacological action for more than 24 h as compared to free drug famotidine which showed its action only upto 12 h.
 Conclusion: Thus the famotidine loaded niosomal formulation may be considered as a very promising drug delivery system which could be successfully employed for prolonging the drug release and overcoming the drawbacks of conventional drug delivery systems.

Optimization of cosmetic formulations development using Box-Behnken design with response surface methodology: physical, sensory and moisturizing properties

Considering the importance of an adequate composition of the formulation in the development of stable, safe and effective cosmetic products, experimental design techniques are tools that can optimize the formulation development process. The objective of this study was to develop topical formulations using the Box-Behnken design with response surface methodology and evaluate its physical, sensory and moisturizing properties. The experimental design used in the first step allowed to identify and to quantify the influence of raw materials, as well as the interaction between them. In the second step, the analysis identified the influence of soy lecithin, the phytantriol and capric acid triglyceride and caprylic on the consistency index, stickiness and greasiness and skin hydration. Cetearyl alcohol, dicetyl phosphate and cetyl phosphate 10EO and acrylates/C10-30 alkylacrylate crosspolymer showed effects in rheological parameters. The addition of soy lecithin had significant effects in terms of consistency index, stickiness, oiliness and immediate moisturizing effects. Phytantriol showed effects on increasing consistency index and oiliness sensation. Thus, the experimental design was shown to be an effective tool for research and development of cosmetics, since it allowed the assessment of the individual and interaction effects of raw materials in the responses: rheological parameters, sensory and clinical efficacy.

The chemical and ultra-structural analysis of thin plastic films used for surgical attenuation of portosystemic shunts in dogs and cats

The objective of the study was to (1) characterize and compare the chemical composition at the surface, subsurface and in the bulk of thin plastic films used for portosystemic shunt attenuation in their native state and after plasma exposure. (2) Assess the presence, concentration and location of irritant compounds (e.g dicetyl phosphate) within the films.Attenuated Total Reflectance Infrared Spectroscopy (ATR-IR), X-ray Photoelectron Spectroscopy (XPS) and dynamic Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) were used to analyze thirteen thin plastic films. Sample thickness was visualized and measured using Scanning Electron Microscopy (SEM). Sample thicknesses were compared using a one-way ANOVA.XPS reported low phosphorous concentrations (surrogate marker of dicetyl phosphate) between 0.01 and 0.19% wt at the sample surfaces (top 10 nm). There were significant differences between film thicknesses (P < .001) observed by SEM. The ATR-IR and ToF-SIMS identified four distinct surface and bulk chemical profiles: 1) Cellophane, 2) Polypropylene, 3) Modified Cellophane, and 4) Unique. Following plasma immersion for 6 weeks, samples showed little change in film thickness or chemical composition.This study confirmed that films used to attenuate portosystemic shunts were commonly not pure cellophane, with significant variations in surface and bulk chemistry. Suspected irritant compounds were not readily identifiable in significant proportions. Pronounced variability existed in both the thickness and chemical composition of these films (surface vs. bulk). The present findings lead to a legitimate question about the reproducibility of shunt occlusion when using thin plastic films from different origins.

Ascorbic acid derivative-loaded modified aspasomes: formulation, in vitro, ex vivo and clinical evaluation for melasma treatment

Vitamin C (L-Ascorbic acid) has many favourable effects on the skin such as antioxidant, anti-aging and whitening effects. Its instability and low permeability limit its pharmaceutical use in cosmetic and dermatological products. Instead, Mg ascorbyl phosphate (MAP), an ascorbic acid derivative, has the same effect with higher stability is being used. In this work, a vesicular system, aspasomes, containing MAP was developed and evaluated. Aspasomes are multilayered vesicles formed by amphiphiles molecules, Ascorbyl palmitate (ASP), in combination with cholesterol and charged lipids for drug encapsulation. Here, we investigated the use of lecithin instead of the charged lipid dicetyl phosphate for aspasomes development. Nine formulations were prepared and evaluated for their entrapment efficiency, particle size, polydispersity index (PDI) and zeta potential. Their entrapment efficiency ranged from 33.00 ± 2.27 to 95.18 ± 1.06, while their particle size was from 373.34 ± 60.85 to 464.37 ± 93.46 nm with acceptable PDI (from 0.212 ± 0.068 to 0.351 ± 0.061) and zeta potential (from −37.52 ± 2.42 to −50.36 ± 1.82). Three formulations were selected and evaluated for their drug release, permeation and retention into skin. One formulation was selected to be formulated as aspasomal topical cream and gel. The aspasomal cream was found to have enhanced drug permeation and skin retention over the aspasomal gel as well as the aspasomes formulation. MAP aspasomal cream was evaluated clinically as an effective treatment for melasma against 15% trichloroacetic acid (TCA) and the results recorded that the aspasomal cream showed the greatest degree of improvement regarding the hemi-MASI scores with 35% of patients rating it as excellent treatment. The study showed that MAP aspasomal cream can be considered a novel treatment of melasma which is free of side effects. Its efficacy as a monotherapy is superior to that of chemical peeling using 15% TCA.

Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.

Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.

Emulsion-templated synthesis and in vitro characterizations of niosomes for improved therapeutic potential of hydrophobic anti-cancer drug: tamoxifen

Hydrophobic nature of anti-cancer drugs not only imparts different pharmacokinetic barriers in drug delivery, but also associates with off-target toxicity and low-dose exposure of drug at the tumor site which is subsequently responsible for the development of multi-drug resistance. This study describes a water-in-oil emulsion templated reverse-phase evaporation strategy, using Span 120 as non-ionic surfactant, for the synthesis of tamoxifen-loaded niosomes. The dicetyl phosphate and Span 120 were used to engineer niosomes for sustained drug release over 12 h and improved surface morphology. The spherical niosomes were 260–300 nm in size with − 34.6 mV zeta potential. The scanning electron microscopy revealed a rough texture on the surface of niosomes. Niosomes released the drug in first-order and sustained release pattern up to 12 h. Cholesterol was embedded in the outer hydrophobic surface of niosomes, via inclusion in oil phase, to enhance the interaction with lipid bilayer of the cells. Niosomes were able to improve the cellular uptake of tamoxifen and introduced apoptosis (29%) as major mechanism of cell death as compared to necrosis (17%). DSC and XRD studies revealed the crystalline nature of the drug inside niosomes while FTIR displayed chemical stability of the drug after entrapment. After encapsulation inside niosomes, the anti-cancer activity of tamoxifen was improved up to five times with IC50 reduced from 1 μM to 0.2 μM against MCF-7 cells. Cytotoxicity and sulforhodamine B assay revealed the apoptotic cell death. The unloaded niosomes alone showed no toxicity to the cells and presented a biocompatible nanoscale delivery platform for hydrophobic anti-cancer drugs.