Mohamed M. Badran

Itraconazole-hydroxypropyl-β-cyclodextrin loaded deformable liposomes: In vitro skin penetration studies and antifungal efficacy using Candida albicans as model

The study aimed to develop novel ITZ-loaded deformable liposomes (DL) in presence of hydroxypropyl-β-cyclodextrin (HPβCD) (DL-CD) to enhance antifungal activity. These formulations have been reported as conceivable vesicles to deliver drug molecules to the skin layers. The efficiency of the prepared systems was compared with conventional liposomes (CL) and ITZ solution. The developed liposomes were characterized for particle size, entrapment efficiency (EE %), deformability, stability, and morphology of the vesicles. In addition, ex vivo penetration and antifungal activity were evaluated. It was found that the presence of HPβCD played a significant role in reducing the vesicle size to nano range. The deformability study and TEM images revealed that membrane deformability of DL and DL-CD was much higher than that of CL. Moreover, DL-CD enhanced the amount of ITZ in SC and deeper skin layers compared to DL and CL. The antifungal activity of ITZ-loaded deformable liposomes remained intact compared to ITZ solution. It can be concluded that deformable liposomes in the presence of HPβCD may be a promising carrier for effective cutaneous delivery of ITZ.

Evaluation of Skin Permeation and Analgesic Activity Effects of Carbopol Lornoxicam Topical Gels Containing Penetration Enhancer

The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31u2009μg/cm2/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation.

Utilizing Pluronic F‐127 and Gelucire 50/13 Solid Dispersions for Enhanced Skin Delivery of Flufenamic Acid

Strategy, Management and Health Policy Preclinical Research

Influence of the Flexible Liposomes on the Skin Deposition of a Hydrophilic Model Drug, Carboxyfluorescein: Dependency on Their Composition

This study focuses on the effect of different flexible liposomes containing sodium cholate, Tween 80, or cineol on skin deposition of carboxyfluorescein (CF). Size distribution, morphology, zeta potential, and stability of the prepared vesicles were evaluated. The influence of these systems on the skin deposition of CF utilizing rat skin as membrane model was investigated. Results showed that all of the investigated liposomes had almost spherical shapes with low polydispersity (PDIu2009<u20090.3) and particles size range from 83 to 175u2009nm. All liposomal formulations exhibited negative zeta potential, good drug entrapment efficiency, and stability. In vitro skin deposition data showed that flexible liposomes gave significant deposition of CF on the skin compared to conventional liposomes and drug solutions. This study revealed that flexible liposomes, containing cineole, were able to deliver higher amount of CF suggesting that the hydrophilic drugs delivery to the skin was strictly correlated to the vesicle composition.

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin–chitosan nanogels (PR–CNG–ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR–CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR–CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR–CNG–ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR–CNG–ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR–CNG–ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR–CNG–ER are promising drug carriers to target liver cancer.

Effect of terpene liposomes on the transdermal delivery of hydrophobic model drug, nimesulide: Characterization, stability and in vitro skin permeation

This study evaluates the ability of the terpenes incorporated in liposomes on thexa0in vitroxa0skin delivery of hydrophobic model drug, nimesulide (NE). To this purpose, so-called terpene liposomes (TPs), which are composed of phospholipid and three types of terpene, citral, limonene and cineole. The obtained formulations were characterized in terms of size distribution, zeta potential and morphology. The efficiency of TPs on skin delivery of NE was studied usingxa0in vitroxa0Franz diffusion cells and abdominal rat skin in comparison with conventional liposomes and ethanolic solutions of NE. Results showed that all the used TPs had spherical structures with negative zeta potential, low polydispersity (PDI < 0.2), nanometric size range (z-average no more than 150 nm). TPs improved the entrapment efficiency (EE%) and gave good physical stability.xa0In vitroxa0skin permeation data showed that TPs were able to give a significant improvement of NE permeation through the rat skin in comparison with conventional liposomes and drug solution. Moreover, the TPs prepared with limonene were also able to deliver a higher amount of NE than the other formulation, thus suggesting that NE delivery to the skin was strictly correlated to type of terpenes incorporated liposomes. n n xa0 n n Key words:xa0Nimesulide, terpene liposomes,xa0in vitroxa0skin permeation.

Simvastatin-loaded nanostructured lipid carriers attenuate the atherogenic risk of erythrocytes in hyperlipidemic rats

&NA; This study aimed to investigate the effect of simvastatin (SV) loaded nanostructured lipid carriers (SV loaded NLCs) on atherogenic index (AI), erythrocytes membrane lipid and antioxidant/pro‐oxidant status in hyperlipidemic rats. SV loaded NLCs were successfully prepared with desired nano‐particles size, spherical shape, high encapsulation efficiency (EE %) and sustained SV release. The results of biological studies revealed that administration of SV loaded NLCs to rats increased SV bioavailability compared to SV suspension. Intraperitoneal injection of tyloxapol as hyperlipidemic agent induces a significant increase of plasma AI, uric acid, lipid peroxidation and protein oxidation. While, plasma total antioxidant capacity and paraoxonase‐1 activity were significantly decreased. Moreover, tyloxapol induced‐hyperlipidemia increases erythrocytes membrane cholesterol and deteriorates erythrocytes antioxidant enzyme activity, GSH/GSSG ratio and NO level However, the propagation of erythrocytes pro‐oxidant activity and hemolysis was observed. On the contrast, the treatment of these rats with SV loaded NLCs improved the measured parameters compared to rats received SV suspension and hyperlipidemic rats. The predominant effect of SV loaded NLCs may be attributed to the enhancement of absorption, prolonged duration and improvement of bioavailability of SV. Accordingly, SV loaded NLCs showed advantageous effects on the blood lipid levels and atherogenic risk of erythrocytes in hyperlipidemic conditions compared to SV suspension. Graphical abstract Figure. No caption available.

Erythrocyte nanovesicles: Biogenesis, biological roles and therapeutic approach: Erythrocyte nanovesicles

Nanovesicles (NVs) represent a novel transporter for cell signals to modify functions of target cells. Therefore, NVs play many roles in both physiological and pathological processes. This report highlights biogenesis, composition and biological roles of erythrocytes derived nanovesicles (EDNVs). Furthermore, we address utilization of EDNVs as novel drug delivery cargo as well as therapeutic target. EDNVs are lipid bilayer vesicles rich in phospholipids, proteins, lipid raft, and hemoglobin. In vivo EDNVs biogenesis is triggered by an increase of intracellular calcium levels, ATP depletion and under effect of oxidative stress conditions. However, in vitro production of EDNVs can be achieved via hypotonic treatment and extrusion of erythrocyte. NVs can be used as biomarkers for diagnosis, monitoring of therapy and drug delivery system. Many therapeutic agents are suggested to decrease NVs biogenesis.

Multifunctional carbamazepine loaded nanostructured lipid carrier (NLC) formulation

Graphical abstract Figure. No Caption available. Abstract Carbamazepine is a valuable pharmacological agent prescribed in treatment of epilepsy and trigeminal neuralgia. Poor bioavailability, successive dose adjustments and reported long term toxic effects are the main hurdles associated with carbamazepine oral administration. Bees wax containing NLC formulations were developed using high shear homogenization/sonication technique to overcome drug limitations. Formulations were successfully produced and evaluated for both in vitro and in vivo assessments. Results showed particles in nanometric range with negative surface charge and satisfying encapsulation efficiencies (from 93.1 ± 7.6 to 95.7 ± 5.6%). In vitro release studies revealed biphasic pattern and faster release was accompanied with higher bees wax concentration. Interaction between drug and NLC components was assessed using infrared and thermal analysis. Using validated chromatographic analytical method, selected formulation showed good pharmacokinetic profile depriving from plasma fluctuation with 2.27‐fold and 1.83‐fold improved bioavailability compared to conventional drug suspension and Tegretol™ suspension respectively. It also showed stronger anticonvulsant activity, with respect to conventional drug suspension, in terms of seizure latency, frequency and duration. Toxicity studies revealed undetectable liver or testicular toxicity in biochemical, histological and immunohistochemical investigations verifying its superiority above other investigated formulations. Collectively, results indicate potential suitability of NLC system to effectively and safely deliver carbamazepine orally.

Crosstalk of Nanosystems Induced Extracellular Vesicles as Promising Tools in Biomedical Applications

Hybrid vesicles are considered as a bridge between natural nanosystems (NNSs) and artificial nanosystems (ANSs). NNSs are extracellular vesicles (EVs), membranous, bio-formed endogenously, which act as endogenous cargoes, and reflecting cellular dynamics. EVs have cellular tropism, permeate tight junctions, and are non-immunogenic. EVs are used as tools in the development of diagnostic and therapeutic agents. ANSs can induce biogenesis of hybrid vesicles as promising smart diagnostic agents, and innovative drug cargoes. EVs can encapsulate small molecules, macromolecules, and ANSs. The manipulation of EVs during biogenesis was suggested for engineering hybrid EVs. This review article highlights the role of ANSs in the biogenesis of NNSs, and introduces hybrid nanosystems research.