Development of chitosan lipid nanoparticles to alleviate the pharmacological activity of piperine in the management of cognitive deficit in diabetic rats.

The aim of the present study was to prepare and evaluate Piperine (PP) loaded chitosan lipid nanoparticles (PP-CLNPs) to evaluate its biological activity alone or in combination with the antidiabetic drug Metformin (MET) in the management of cognitive deficit in diabetic rats. Piperine was successfully loaded on CLNPs prepared using chitosan, stearic acid, Tween 80 and Tripolyphosphate (TPP) at different concentrations. The developed CLNPs exhibited high entrapment efficiency that ranged from 85.12 to 97.41%, a particle size in the range of 59.56-414 nm and a negatively charged zeta potential values (- 20.1 to - 43.9 mV). In vitro release study revealed enhanced PP release from CLNPs compared to that from free PP suspensions for up to 24 h. In vivo studies revealed that treatment with the optimized PP-CLNPs formulation (F2) exerted a cognitive enhancing effect and ameliorated the oxidative stress associated with diabetes. PP-CLNPs acted as an effective bio-enhancer which increased the potency of metformin in protecting brain tissue from diabetes-induced neuroinflammation and memory deterioration. These results suggested that CLNPs could be a promising drug delivery system for encapsulating PP and thus can be used as an adjuvant therapy in the management of high-risk diabetic cognitive impairment conditions.

Formulation of tizanidine hydrochloride-loaded provesicular system for improved oral delivery and therapeutic activity employing a 23 full factorial design.

Tizanidine hydrochloride (TZN) is one of the most effective centrally acting skeletal muscle relaxants. The objective of this study is to prepare TZN-loaded proniosomes (TZN-PN) aiming at enhanced oral delivery and therapeutic activity. TZN-PN were prepared by coacervation phase separation method. The developed vesicles were characterized via entrapment efficiency percentage (EE%), vesicular size (VS), and zeta potential (ZP). A 23 full factorial design was employed to attain an optimized TZN-PN formulation. The optimized TZN-PN were further characterized via in vitro release study and transmission electron microscopy (TEM). In vivo rotarod test was employed for determination of the muscle relaxant activities of rats and levels of GABA and EAAT2 were detected. The developed TZN-PN exhibited relatively high EE% (75.78-85.45%), a VS ranging between (348-559 nm), and a ZP (-26.47 to -59.64). In vitro release profiles revealed sustained release of TZN from the optimized TZN-PN, compared to free drug up to 24 h. In vivo rotarod study revealed that the elevation in coordination was in the following order: normal control < free TZN < market product < TZN-PN (F6). Moreover, the optimized TZN-PN exhibited significant elevated coordination activity by 39% and 26% compared to control group and market product group, respectively. This was accompanied with an elevation in both GABA and EAAT2 serum levels. Thus, it could be concluded that encapsulation of TZN in the provesicular nanosystem proniosomes has enhanced the anti-nociceptive effect of the drug and consequently its therapeutic activity.

Cubosomes as a Potential Oral Drug Delivery System for Enhancing the Hepatoprotective Effect of Coenzyme Q10.

Coenzyme Q10 (CoQ10) acts as an antioxidant that protects the cells by preventing lipid peroxidation. Owing to its low solubility, CoQ10 has shown poor delivery properties and poor bioavailability. The aim of this study is to develop CoQ10 loaded cubosomes in order to enhance its oral delivery and hepatoprotective activity. Cubosomes are cubic nanostructured systems resulting from the colloidal dispersion of cubic liquid crystalline structure in water. CoQ10 loaded cubosomes were prepared using poloxamer 407 and glyceryl monooleate at three weight ratios (1:2.5, 1:5 and 1:7.5) and were further characterized. They were investigated for their hepatoprotective effect in thioacetamide (TAA) induced hepatotoxicity in Wistar rats. The developed CoQ10 cubosomes exhibited moderate to high entrapment efficiency percentages (44.69-75.96%), nanometric dimensions (132.4-223.2 nm), and negatively charged zeta potential values (<-21.3). In-vitro release profiles showed a sustained release of CoQ10 from the developed cubosomes up to 48 h. In-vivo study revealed an improved hepatoprotective effect of CoQ10 cubosomes via reducing liver enzymes, nitric oxide and malondialdehyde as well as elevating phosphoinositide 3-kinase, catalase and glutathione peroxidase, compared to plain drug. These results were in good agreement with histopathological investigations. Consequently, the developed cubosomes showed a potential effect in enhancing the hepatoprotective activity of CoQ10.

Provesicular elastic carriers of Simvastatin for enhanced wound healing activity: An in-vitro/in-vivo study.

The aim of this study was to prepare and evaluate simvastatin (SIM) loaded elastic provesicular systems for effective topical wound management. SIM provesicles were prepared using the non-ionic surfactant Span 40, cholesterol and three edge activators i.e. Span 80, Tween 80 and sodium cholate. The vesicles revealed high SIM encapsulation efficiency ranging from 87.25 to 98.15%, whereas vesicle sizes ranged from 462.3 to 801.5 nm. Vesicle sizes decreased with increasing the concentration of the edge activator. High negative zeta potential values were observed, revealing good stability of the vesicular formulations. The release of SIM from hydrated provesicular carriers was biphasic in nature. The selected SIM provesicular elastic carrier exerted approximately two-fold increase in the amount of SIM permeated through rat skin, compared to the free drug. Evaluation of wound healing activity of the selected provesicular formulation revealed significant reduction in wound size in rats, fourteen days post-wounding. These results were further confirmed by a significant increase in expression of vascular endothelial growth factor and collagen type I compared to the free drug. These results indicate that provesicular carriers could be a promising drug delivery system for encapsulating SIM and enhancing its wound healing efficacy.

Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation.

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl ßeta-cyclodextrin (HPß-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer-Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.

Formulation of Niosomal Gel for Enhanced Transdermal Lornoxicam Delivery: In-Vitro and In-Vivo Evaluation.

BACKGROUND: The objective of this study was to investigate the potential of niosomal gels as a transdermal delivery system to improve the permeation and anti-inflammatory activity of Lornoxicam (LX). METHODS: LX niosomes were prepared by thin film hydration technique and were characterized using Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), Particle Size analysis and Zeta potential determination. LX niosomal gel/LX loaded gel were prepared using Carbopol 934 (2%) and were evaluated for their physical appearance, pH and rheological behaviour. Ex vivo skin permeation test was performed on dorsal region of wistar rats. In vivo studies comprised skin irritation test and anti-inflammatory activity study. RESULTS: The prepared LX niosomes exhibited an entrapment efficiency of more than 66% and a particle size diameter ranging from 295 nm to 1298 nm, with negatively charged zeta potential. TEM electron micrographs revealed spherical shaped vesicles. The release pattern of drug was analyzed and found to follow Higuchi's model. Rheology studies revealed the pseudoplastic behaviour of LX niosomal gel. They exhibited a one and half fold increase in drug permeated through rat skin, when compared to free drug. Skin irritation test proved the non-irritancy of LX niosomal gels, when applied to dorsal region of Wistar rats. Percentage edema inhibition of LX niosomes was significantly higher (P<0.05) than that of free LX group showing an enhanced anti-inflammatory activity of LX niosomes. CONCLUSION: These findings revealed that LX loaded niosomal gels could be a potential transdermal drug delivery system.