Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis.

Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole's well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 µM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 µM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy.

Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin.

Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X1 (oil) and X2 (surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15 min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 ± 1.170 nm, 0.228 ± 0.012, 17.660 ± 1.520 s, and 34.180 ± 1.380 mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were - 28.200 ± 1.200 mV, 99.200% ± 0.600, and 90 °C, respectively. Drug release was found to be 93.320% ± 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.

Application of liquisolid technology for enhancing solubility and dissolution of rosuvastatin.

PURPOSE: Rosuvastatin is a poorly water soluble drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Hence it is necessary to increase the solubility of the Rosuvastatin. METHODS: Several liquisolid tablets formulations containing various drug concentrations in liquid medication (ranging from 15% to 25% w/w) were prepared. The ratio of Avicel PH 102 (carrier) to Aerosil 200 (coating powder material) was kept 10, 20, 30. The prepared liquisolid systems were evaluated for their flow properties and possible drug-excipient interactions by Infrared spectra (IR) analysis, differential scanning calorimetry (DSC) and X- ray powder diffraction (XRPD). RESULTS: The liquisolid system showed acceptable flow properties. The IR and DSC studies demonstrated that there is no significant interaction between the drug and excipients. The XRPD analysis confirmed formation of a solid solution inside the compact matrix. The tabletting properties of the liquisolid compacts were within the acceptable limits. Liquisolid compacts demonstrated significantly higher drug release rates than those of conventional and marketed tablet due to increasing wetting properties and surface area of the drug. CONCLUSION: This study shows that liquisolid technique is a promising alternative for improvement of the dissolution rate of water insoluble drug.

A study on ethosomes as mode for transdermal delivery of an antidiabetic drug.

CONTEXT: A transdermal delivery system is warranted for repaglinide (RPG) which possesses half-life of 1 h and oral bioavailability of 56%. Ethosomes are useful tools for transdermal drug delivery. OBJECTIVES: To prepare and evaluate ethosomes as mode for transdermal delivery of RPG. MATERIAL AND METHODS: Ethosomes loaded with RPG were prepared from dipalmitoyl phosphatidylcholine and ethanol by the cold method. They were characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. They were evaluated for vesicle size, entrapment efficiency and ex-vivo skin permeation. Ethosomal composition was optimized using the 3(2) factorial design. Gel containing optimzsed ethosomes was studied for antidiabetic activity in rats. RESULT: RPG ethosomes possessing the size of 0.171-1.727 µm and entrapment efficiency of 75-92% were obtained. They demonstrated a significantly higher permeation (64-97% of the administered dose) across excised rat skin when compared to free drug and its hydro alcoholic solution. In-vivo, RPG ethosomal system caused sustained antidiabetic effect. DISCUSSION: The lipid and ethanol concentration affected the physicochemical attributes and performance of ethosomes. The flexible ethosomes permeated the stratum corneum and improvized the availability of RPG for antidiabetic action. They prolonged the antidiabetic effect of RPG over a significantly longer period of time in comparison with the equivalent oral dose. CONCLUSION: Ethosomal system can successfully deliver RPG transdermally; sustain its effect and thus reduce its dosing frequency. Ethosomes are useful for enhancing the efficacy of RPG in the treatment of diabetes.

Studies on nonionic surfactant bilayer vesicles of ciclopirox olamine.

CONTEXT: Niosomal delivery can prove an alternative to improve the poor skin penetration and residence of the topical antifungal drugs that account for the long treatment regimes in cutaneous mycosis. OBJECTIVE: To investigate niosomes as carriers for dermal delivery of ciclopirox olamine (CPO), a broad spectrum antifungal drug. MATERIALS AND METHODS: Niosomes were prepared by ethanol injection method using Span 60, cholesterol, diacetyl phosphate according to 3(2) factorial design and evaluated for physicochemical parameters, in vitro and ex vivo deposition in skin and stability study. RESULTS: Unilamellar CPO niosomes of size 170-280 nm, entrapment efficiency 38-68%, and sufficient electrokinetic stability were obtained. Percent drug deposition in artificial membrane varied from 12.75 to 92.74. Deposition of CPO into rat skin from niosomal dispersion and its gel was significantly higher than that of plain CPO solution and its marketed product. Obtained niosomes possessed sufficient stability on storage. DISCUSSION: Increasing amounts of Span 60 and cholesterol increase the vesicle size probably because of entrapment of CPO-ionized molecules in the aqueous compartment and interaction of its unionized counterpart with the bilayer constituents leading to increase in bilayer thickness. Consequently, the percent entrapment efficiency also increased. However, increasing Span 60 levels decreased the in vitro percent drug deposition. This might be attributed to the larger size of vesicles produced by high amounts of surfactant that showed poor deposition. The optimized batch possessed sufficient stability. CONCLUSIONS: The results of this investigation suggest that niosomes are promising tools for cutaneous retention of CPO.