Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation.

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8 ± 18.69 to 797.7 ± 12.45 nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC0-48 hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.

Improved hepatoprotective activity of silymarin via encapsulation in the novel vesicular nanosystem bilosomes.

The main objective of the present work was to formulate, characterize, and evaluate silymarin (SM)-loaded bilosomes, compared to conventional liposomes, aiming at increasing the hepatoprotective activity of the drug. SM-loaded bilosomes were prepared by thin film hydration technique employing soybean phosphatidyl choline (SPC) and different bile salts. After being subjected to different methods of characterization, SM-loaded bilosomes were investigated for their hepatoprotective activity, in CCl4 hepatointoxicated rat model. The developed SM dispersions exhibited an entrapment efficiency ranging from 21.80 ± 2.01 to 84.54 ± 2.51% and a particle size diameter in the nanometric dimensions (413 ± 96.9 to 686.9 ± 62.38 nm), with a negative zeta potential values (<-45 mV). In vitro release study revealed a lower cumulative amount of drug released from the developed formulae, compared to free drug. Ex vivo intestinal uptake study, performed using confocal laser scanning calorimetry, revealed the superiority of bilosomal uptake compared to that of liposomes. In vivo studies revealed an enhanced hepatoprotective effect of SM-loaded bilosomes/liposomes compared to free drug. These results were in good correlation with histopathological examination. These findings support the potential use of bilosomes for improving the hepatoprotective activity of SM via oral administration.

Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection.

BACKGROUND & AIMS: HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment. METHODS: We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance. RESULTS: Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner. CONCLUSIONS: This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance.

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.

Cationic Polymeric Nanoparticles for Improved Ocular Delivery and Antimycotic Activity of Terconazole.

Terconazole (TCZ) is a broad-spectrum antifungal triazole that is particularly active against Candida species, but its poor water solubility hinders its ocular absorption and restricts its application. This study aims to fabricate TCZ-loaded cationic polymeric nanoparticles to enhance the ocular delivery and antimycotic activity of terconazole. TCZ-loaded nanoparticles were developed by nanoprecipitation method employing Eudragit RLPO®. They were characterized by entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), morphology, Fourier transform infrared spectroscopy (FT-IR), and X-ray powder diffraction (XRPD). In-vitro antimycotic activity was evaluated by measuring zone of inhibition (ZI), minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The developed nanoparticles were spherical with moderate to high EE% (44.03-71.14%), a nanometric PS (49.41-78.72 nm), and a positively charged ZP (≥ +21.47). In-vitro release studies revealed sustained release of drug up to 24 h. FT-IR of TCZ-loaded nanoparticles revealed distinctive peaks for Eudragit RLPO® and Poloxamer-188, with disappearance of the TCZ characteristic peaks. XRPD revealed the amorphous state of TCZ within the polymer matrix. Mucoadhesive studies proved the mucoadhesive property of the developed TCZ nanoparticles. In-vitro antimycotic studies, assessed by ZI, MIC and MFC, revealed enhanced antimycotic activity of TCZ-loaded nanoparticles against Candida albicans, relative to plain TCZ. No irritation or abnormal changes to the rabbits' eyes for plain and medicated polymeric nanoparticles were found by the in-vivo Draize test. These findings reveal that the cationic polymeric nanoparticles can be regarded as a potential drug delivery system for enhancing the ocular antimycotic activity of TCZ.

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.

Enhanced corneal permeation and antimycotic activity of itraconazole against Candida albicans via a novel nanosystem vesicle.

The objective of this study was to investigate the potential of spanlastics as an ophthalmic delivery system to improve the corneal permeability and antimycotic activity of itraconazole (ITZ). Spanlastics containing edge activators, including Tween 20 or 80, were produced by modified ethanol injection method and exhibited a particle size of approximately 287 nm and an entrapment efficiency of more than 88%. Less than 13% ITZ was released from spanlastics over 6 h compared to 35% from conventional niosomes. Spanlastics exerted a 1.34-fold increase in the amount of ITZ permeated through excised bovine cornea after 24 h compared to conventional niosomes. Antimycotic study revealed a significant (p < 0.05) increase in the zone of inhibition of Candida albicans culture demonstrated by spanlastics compared to ITZ powder at the same concentration level (10 mg). In vivo Draize test showed no signs of acute ocular toxicity upon application of the selected spanlastic formulation to the rabbit eye. Results revealed that spanlastics loaded with itraconazole could be a potential nanosystem in ocular drug delivery systems.

Prioritizing High-Risk Practices and Exploring New Emerging Ones Associated With Hepatitis C Virus Infection in Egypt.

BACKGROUND: The aim of this study was to identify and prioritize the risky behaviors and explore the newly emerging pi related to Egyptian habits that may lead to HCV transmission. METHODS: From January 2011 until January 2012, a case control study matched on socio demographic factors was conducted comparing 540 hepatitis C patients and their contacts who were HCV serologically negative (102 subjects). They were randomly selected from six governorates representing Upper Egypt, Lower Egypt, Middle and Canal regions. The questionnaire covered demographic data, risk exposures, behaviors, and practices for HCV infection. Focus group discussions were done with groups of professionals in Hepatology to discuss the observed emerging risk practices in Egypt. RESULTS: In univariate analysis, invasive medical procedures, wound stitches, illiteracy and marriage were significantly associated with HCV infection. Among women, delivery at home by traditional birth attendant was associated with 3 times (OR=2.91, CI=1.23-6.98) and 4 times (OR=3.94, CI=1.44-11.35) increase in HCV risk than delivery at hospital and by doctors respectively. Among males, shaving at barbershops was associated with 2 fold increase in the risk of infection (OR=2.6, CI=1.44-4.89). Newly observed emerging risk practices were: sharing scarves' pins by veiled women in same houses, sharing loofah for personal cleaning and sharing toothpaste among family members. CONCLUSION: Increasing risk of HCV infection in Egypt reinforces the need for strict implementation of effective HCV prevention programs according to the prevailing risk behaviours.