Candesartan Cilexetil (CC) is a prodrug widely used in the treatment of hypertension and heart failure, but it has some limitations, such as very poor aqueous solubility, high affinity to P-glycoprotein efflux mechanism, and hepatic first-pass metabolism. Therefore, it has very low oral bioavailability. In this study, glyceryl monostearate (GMS) and Capryol™ 90 were selected as solid and liquid lipids, respectively, to develop CC-NLC (nanostructured lipid carrier). CC was successfully encapsulated into NLP (CC-NLC) to enhance its oral bioavailability. CC-NLC was formulated using a hot homogenization-ultrasonication technique, and the physicochemical properties were characterized. The developed CC-NLC formulation was showed in nanometric size (121.6 ± 6.2 nm) with high encapsulation efficiency (96.23 ± 3.14%). Furthermore, it appeared almost spherical in morphology under a transmission electron microscope. The surgical experiment of the designed CC-NLC for absorption from the gastrointestinal tract revealed that CC-NLC absorption in the stomach was only 15.26% of that in the intestine. Otherwise, cellular uptake study exhibit that CC-NLCs should be internalized through the enterocytes after that transported through the systemic circulation. The pharmacokinetic results indicated that the oral bioavailability of CC was remarkably improved above 2-fold after encapsulation into nanostructured lipid carriers. These results ensured that nanostructured lipid carriers have a highly beneficial effect on improving the oral bioavailability of poorly water-soluble drugs, such as CC.

The current study inspects the screening of the formulation components further, evaluates the physicochemical properties of the nanostructured lipid carriers (NLCs) for the antihypertensive drug as Candesartan Cilexetil (CC). The sequence screening of all excipients required for the preparation of NLCs should be performed. Firstly, the solubility of CC in different solid and liquid lipids is the major parameter for the selection of the best one. Precirol® ATO 5, Compritol ® 888 ATO and Glyceryl Monostearate (GMS) were showed the maximum solubility of the CC (1000±4.12 mg, 1500±4.15 mg and 1750±3.16 mg), respectively. Hence, they were selected as the solid lipids for the development of NLCs. Liquid lipids Transcutol® HP (30±2.21 mg/ml), Labrasol® ALF (25±1.32 mg/ml) and CapryolTM 90 (18±1.34 mg/ml) were observed to have good affinity for the drug on systematic screening of different liquid lipids. However, Precirol® ATO 5 was found to has good physical compatibility with Transcutol® HP, Compritol ATO 888 was found to has high physical miscibility with Labrasol® ALF and last GMS was appeared in good affinity and compatibly with CapryolTM 90. Hence, the following binary lipid mixtures (Precirol® ATO 5 - Labrasol® ALF), (Compritol® 888 ATO-Transcutol® HP) and (GMS - CapryolTM 90) were selected for the preparation of NLCs. The liquid–solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (55-59 0C). Lutrol F-68, Lutrol F-127, Cremophore EL and Cremophore® RH. In addition to, the combination of (Lutrol® F68:Cremophore® EL) and (Lutrol® F127: Cremophore® RH) were selected as the main surfactants for the preparation of NLCs formulations because of its good emulsification efficacy and homogeneity for the solid-liquid lipid mix. The prepared formulations were investigated for the different quality issues. All designed formulations observed in nanometer size of particles ranged from (408.9±11.5 to 114.6±8.3 nm) with high encapsulation efficiency around 99%. Also, the obtained results revealed that the ZP of the various formulations was consistently negative surface charge in between ((-13 ±2.3 to27.3±3.7 mV). Finally, formula number nine of CC (CC-NLC9) which composed of GMS (solid lipid), CapryolTM 90 (liquid lipid) and Lutrol® F127: Cremophore® RH (surfactants combination) was selected as the best formulation after the rank order for further investigations in the next work.  Peer Review History: UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Name: Dr. Mohammed Abdel-Wahab Sayed Abourehab Affiliation: Umm Al-Qura University;  Makkah Al-Mukarramah, Saudi Arabia E-mail: maabourehab@uqu.edu.sa   Name: Dr.  Maha Khalifa Ahmed Khalifa    Affiliation: Al-Azhar Universit - Cairo, Egypt E-mail: mahakhalifa.ahmed@hotmail.com   Name: Dr. Evren Alğin Yapar Affiliation: Turkish Medicines and Medical Devices Agency, Turkiye E-mail: evren.yapar@yahoo.com Comments of reviewer(s): Similar Articles: FORMULATION AND CHARACTERIZATION OF TOPICAL NANO EMULGEL OF TERBINAFINE A REVIEW ON GOLD NANOPRTICLES SYNTHESIS AND CHARACTERIZATION FORMULATION AND EVALUATION OF ELASTIC LIPOSOMES OF DECITABINE PREPARED BY ROTARY EVAPORATION METHOD

Objectives: The aim of the study was to develop a proniosomal carrier system that is capable of efficiently delivering entrapped glimepiride over an extended period of time for the treatment of type 2 diabetes. Methods: Proniosomal gels were developed based on span 60 with and without cholesterol. The entrapment efficiency of drug inside niosomes developed from hydration of the proniosomes gel was also characterized. The in vitro release and skin permeation of glimepiride from various proniosomes gel formulations were investigated. The stability studies were performed at 4°C and at room temperature. Results: The maximum entrapment efficiency was obtained when the cholesterol concentration was 10% of total lipid (90.02%). In vitro release through mixed cellulose ester membrane showed sustained release of drug from proniosomes gels. In vitro drug permeation across rabbit skin revealed improved drug permeation and higher transdermal flux with proniosomes gels compared to hydro-alcoholic gel of drug. Also, good physical stability was also achieved with proniosomes gels. Kinetics of in vitro skin permeation showed diffusion model of drug release from formulations. Conclusion: The study proved that the concentration of cholesterol had great influence on the properties of proniosomes gels. Hence, proniosomes preparation containing 10% cholesterol can significantly increase trans-epidermal flux and prolong the release of glimepiride. Cite this article-Elsaied EH, Dawaba HM, Ibrahim EA, Afouna MI. Investigation of proniosomes gel as a promising carrier for transdermal delivery of Glimepiride.

Objective: The objective of this current study is to fabricate ocuserts to control the drug release from chosen bioadhesive polymeric matrixes to enhance patient compliance. Ciprofloxacin HCl (CFX HCl) was selected as a model drug.Methods: Different bioadhesive polymers with different film forming capabilities namely Hydroxy Propyl Methyl Cellulose (HPMC K4M), Poly Vinyl Alcohol (PVA), Sodium Carboxy Methyl Cellulose (Na CMC), Hydroxy Propyl Cellulose (HPC), Sodium Alginate (Na Alg.), pullulan and Xanthan Gum (XG) in different ratios were used in fabricating ocuserts using solvent-casting technique. Propylene Glycol (PG) was used as a plasticizer to facilitate the fabrication process. Characterization tests of the developed ocuserts were performed as well as bioadhesive tests and in vitro release studies of the incorporated drug. The obtained results were analysed using different release kinetic models. Stability of the selected ocuserts was investigated at 40±0.5 °C and 75±5% Relative Humidity (RH) for three months’ storage period. In vivo ocular irritation test was performed to investigate the safety of the formula in rabbits’ eyes as well as to test the release profile and thus to estimate In vitro In vivo correlation.Results: All the prepared ocuserts showed the uniformity of film characterization and bioadhesion strength ranged from 240±66 and 158±52dyne/cm2. Selected formula from the in vitro release study tested for in vivo study showed the slow release of ciprofloxacin drug up to 24 h with no signs of eye irritancy. Results for In vitro In vivo correlation showed an excellent correlation with R2 value of 0.9982.Conclusion: PVA based ocuserts proven to be a promising once-daily, effective and safe ocular delivery system of the drug.

In recent years, Span 60 based nanovesicles have been the object of growing scientific attention as an alternative potential drug delivery system to conventional liposomes. Surface modification of nanovesicles can adjust the drug release rate and the affinity for the target site. The aim of present work was firstly to study the effects of different PEGylated edge activator (Myrj 52 and Myrj 59) on Span 60 based nanovesicles. Nanovesicles were prepared using Span 60 alone or in combination with Myrj 52 (polyethylene glycol 2000 monostearate) or Myrj 59 (polyethylene glycol 4400 monostearate) by employing the ethanol injection method. Myrj 52and Myrj 59 are hydrophilic nonionic surfactants were used to modify the surface of the developed vesicles. Dynamic light scattering was used to determine the size, zeta potential and polydispersity index of the nanovesicles formulation. The vesicles were also characterized for entrapment efficiency and in vitro release. In current work, the modified nanovesicles size (ranging from 54.32 to 141.7 nm), zeta potential (ranging from -5.67 to -27.1 mV) and polydispersity index (ranging from0.248 to 0.531) indicated that the surface modified nanovesicles vesicles are a homogenous and mono-disperse nanovesicles dispersions. The non-modified nanovesicles are showed higher particles size (>2 times) compared to modified nanovesicles. The modified nanovesicles were showed entrapment efficiency ranging from 36.42 to 78.13 %. All the modified nanovesicles showed accepted in vitro release of TN from nanovesicles (>70% released after 8 h), followed Higuchi models as drug release mechanism. In conclusion, these surface modified nanovesicles could be used as a potential drug carrier for a variety of drugs.

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Background: Chitosan, a naturally occurring polymer, has interesting applications in the field of drug delivery due to its plentiful advantages as biodegradability, biocompatibility and nontoxic nature. Nigella sativa essential oil is unstable, volatile, and insoluble in water and these problems confine its usage in developing new medicines. Objective: This study focuses on developing a chitosan-based nanocarrier for the encapsulation of Nigella Sativa essential oil. By using Quality by design outline, the quality target product outline, critical quality attributes and critical material attributes were defined by knowledge and risk-based procedures. Method: According to defined critical material attributes, Optimization software (Statgraphics XVII) was used to study the effect of the processing parameters. The processing parameters identified and fixed first with a “One factor at a time” approach. Various physicochemical characterization techniques were performed. Results: As a result, the ratio of chitosan to benzoic acid (2:1) along with the stirring rate (4000 rpm) produced minimum-sized particles (341 nm) with good stability. The anti-bacterial activity study using Staph. Aureus strain proved that the optimized nanoparticles were more efficacious than the pure oil based on the diameter of inhibition zone obtained (diameter =5.5 cm for optimized formula vs diameter = 3.6 cm for pure oil). Furthermore, MTT (methyl thiazolyl-diphenyl-tetrazolium bromide) assay was performed to compare the in vitro cytotoxicity using two different cell lines (i.e. HCT 116 for colorectal carcinoma and PC3 for prostatic cancer). It was found that in both cell lines, the optimized nanoparticles had noteworthy antiproliferative properties illustrated by determining the concentration at which 50% of growth is inhibited (IC50). The optimized nanoparticles showed lower IC50 (17.95 ±0.82 and 4.02 ±0.12μg/ml) than the bare oil IC50 (43.56 ±1.95 and 29.72 ±1.41μg/ml).

Curcumin (C), a natural anticancer agent suffers extremely low aqueous solubility and rapid systemic elimination, therefore, the aim from the present study was to develop and optimize biocompatible, biodegradable solid lipid nanoparticles containing curcumin (CSLNs) using Solvent Injection Method. The components selected to develop the SLNs were Glycerol MonoStearate (GMS; the lipidic carrier), Poloxamer 407 (P407; Surfactant) and Ethanol (solvent for the drug and the lipidic carrier). The combination and ratios for the optimization process were carried out using 2 3 full-factorial designs. The experimental design runs (8 formulations H1-H8) were prepared and the design dependent responses (assessment of particle size, Entrapment Efficiency % and the in vitro release study) were characterized. The developed formulae showed a nanometric particle size range (203.0-345.0nm), high Entrapment Efficiency % (62.77-87.42 %) and prolonged release over 24 hr periods (55.97-89.64 %). These results were analyzed using JMP ® 10 software and its analytical tools were used to draw Pareto charts and the interactions plots. On the basis of the software analysis, formulation H9 with a desirability factor of 0.582 was selected as the optimized formulation and was evaluated for the dependent responses. Formulation H9 showed a particle size of 249.1 nm, 74.51 % Entrapment efficiency, 85.72 % in vitro release over 24 hr and these results suggested that the solid lipid nanoparticles formulations could be a promising method to sustain the release of curcumin.