PREPARATION AND EVALUATION OF ANTHRALIN BIODEGRADABLE NANOPARTICLES AS A POTENTIAL DELIVERY SYSTEM FOR THE TREATMENT OF PSORIASIS

Objective: Anthralin is one of the most effective drugs in psoriasis management. However, its side effects and unfavourable physicochemical properties limit its clinical use. Therefore, the objective of this study was to prepare and evaluate poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-b-PCL) nanoparticles as a potential delivery system for anthralin.Methods: PEG-b-PCL nanoparticles were prepared by the co-solvent evaporation method and evaluated using a variety of techniques. The effect of drug/polymer weight feed ratio on the nanoparticle size, drug loading capacity and encapsulation efficiency were studied. Drug release kinetics were studied using the dialysis bag method. Nanoparticle size was measured using dynamic light scattering and confirmed by transmission electron microscopy measurements.Results: PEG-b-PCL formed spherical nanoparticles having a diameter of 40 to 80 nm based on the polymer and level of drug loading. The size observed by TEM measurements was slightly smaller than that obtained by DLS due nanoparticle dryness during measurement. Drug loading capacity increased with increasing the drug/polymer ratio and a maximum loading of ~25% was obtained. Anthralin encapsulation in the nano particles resulted in ~120-fold increase in its aqueous solubility. Anthralin was released from the nanoparticles over a prolonged period of time where ~ 45% was released in 48 h.Conclusion: These results confirm the utility of PEG-b-PCL nanoparticles in enhancing the aqueous solubility and sustaining the release of athralin. Therefore, they might be used as a potential delivery system for the treatment of psoriasis.Â

SELF-ASSEMBLING HYDROGELS BASED ON Î’-CYCLODEXTRIN POLYMER AND POLY (ETHYLENE GLYCOL) BEARING HYDROPHOBIC MOIETIES FOR PROTEIN DELIVERY

Objective: The development of injectable and stable hydrogels for protein delivery is a major challenge. Therefore, the objective of this study was to evaluate the potential of polymerized β-CD for the formulation of stable hydrogels suitable for loading and release of bioactive agents and to investigate the mechanism of hydrogel formation. Methods: Hydrogels based on the inclusion complexation of polymerized β-cyclodextrin and cholesterol terminated poly(ethylene glycol) polymers were formed by rehydration of a lyophilized mixture of both polymers. The mechanism of hydrogel formation was investigated via isothermal titration calorimetry, fluorescence spectroscopy and dynamic light scattering measurements. The release behavior of bovine serum albumin (BSA) as a model protein from the modified gels was explored. Results: Rheological analysis demonstrated that the prepared hydrogels had a viscoelastic behavior even at elevated temperature (> 37 ˚C). There are two competing mechanisms for hydrogel formation. The first mechanism is the inclusion complexation between cholesterol moieties and β-CD cavities. The second one is the self association of cholesterol modified PEGs. β-CD had the ability to dissociate the PEG-cholesterol associations. The quantitative and complete release of BSA was observed within 4 weeks. Conclusion: The polymerized form of β-CD, rather than native β-CD is essential for the formation of stable hydrogels. These results were supported by the ability of the modified hydrogel system for loading and release of BSA, making such hydrogel systems promising devices in drug delivery applications

Enhanced skin deposition and delivery of voriconazole using ethosomal preparations.

Despite its broad-spectrum antifungal properties, voriconazole has many side effects when administered systemically. The aim of this work was to develop an ethosomal topical delivery system for voriconazole and test its potential to enhance the antifungal properties and skin delivery of the drug. Voriconazole was encapsulated into various ethosomal preparations and the effect of phospholipid and ethanol concentrations on the ethosomes properties were evaluated. The ethosomes were evaluated for drug encapsulation efficiency, particle size and morphology and antifungal efficacy. Drug permeability and deposition were tested in rat abdominal skin. Drug encapsulation efficiency of up to 46% was obtained and it increased with increasing the phospholipid concentration, whereas the opposite effect was observed for the ethanol concentration. The ethosomes had a size of 420–600 nm and negative zeta potential. The particle size of the ethosomes increased by increasing their ethanol content. The ethosomes achieved similar inhibition zones against Aspergillus flavus at a 2-fold lower drug concentration compared with drug solution in dimethyl sulfoxide. The ex vivo drug permeability through rat abdominal skin was ∼6-fold higher for the ethosomes compared with the drug hydroalcoholic solution. Similarly, the amount of drug deposited in the skin was higher for the ethosomes and was dependent on the ethanol concentration of the ethosomes. These results confirm that voriconazole ethosomal preparations are promising topical delivery systems that can enhance the drug antifungal efficacy and improve its skin delivery

Bees visiting the broad bean (Vicia faba L.) and the impact of border planting on their abundance and the yield improvement in Ismailia, Egypt:

Incorporating flowering plants into cropping systems has the potential to actively enhance pollination and crops yields. This study evaluated whether the introduction of border planting affects bee visitation and yield of a broad bean (Vicia faba L.). Experiments were carried out in 2018 and 2019 in Ismailia, Egypt.  Bee visitation and broad bean yields were compared between plots with and without border planting. Results showed that open flowers achieved higher yields than netted flowers. Apis mellifera L. was the dominant visitor, followed by four solitary bee species, Chalicodoma siculum (Rossi), Colletes lacunatus Dours, 1872, Andrena ovatula and Xylocopa pubescens (Kirby, 1802).  The addition of border planting was associated with a significant increase in the abundance of all five bee visitors and the associated yields. Findings showed that flowering border plants adjacent to broad bean can actively enhance pollination services and yields of this commercially valuable crop, whilst helping to conserve vulnerable bee populations

Rutin Nanocrystals with Enhanced Anti-Inflammatory Activity: Preparation and Ex Vivo/In Vivo Evaluation in an Inflammatory Rat Model

Rutin is a polyphenolic flavonoid with an interestingly wide therapeutic spectrum. However, its clinical benefits are limited by its poor aqueous solubility and low bioavailability. In an attempt to overcome these limitations, rutin nanocrystals were prepared using various stabilizers including nonionic surfactants and nonionic polymers. The nanocrystals were evaluated for particle size, zeta potential, drug entrapment efficiency, morphology, colloidal stability, rutin photostability, dissolution rate, and saturation solubility. The selected nanocrystal formulation was dispersed in a hydrogel base and the drug release kinetics and permeability through mouse skin were characterized. Rutin’s anti-inflammatory efficacy was studied in a carrageenan-induced rat paw edema model. The nanocrystals had a size in the range of around 270–500 nm and a polydispersity index of around 0.3–0.5. Nanocrystals stabilized by hydroxypropyl beta-cyclodextrin (HP-β-CD) had the smallest particle size, highest drug entrapment efficiency, best colloidal stability, and highest drug photostability. Nanocrystals had around a 102- to 202-fold and 2.3- to 6.7-fold increase in the drug aqueous solubility and dissolution rate, respectively, depending on the type of stabilizer. HP-β-CD nanocrystals hydrogel had a significantly higher percent of drug released and permeated through the mouse skin compared with the free drug hydrogel. The cumulative drug amount permeated through the skin was 2.5-fold higher than that of the free drug hydrogel. In vivo studies showed that HP-β-CD-stabilized rutin nanocrystals hydrogel had significantly higher edema inhibition compared with the free drug hydrogel and commercial diclofenac sodium gel. These results highlight the potential of HP-β-CD-stabilized nanocrystals as a promising approach to enhance drug solubility, dissolution rate, and anti-inflammatory properties

Enhanced skin deposition and delivery of voriconazole using ethosomal preparations.

Despite its broad-spectrum antifungal properties, voriconazole has many side effects when administered systemically. The aim of this work was to develop an ethosomal topical delivery system for voriconazole and test its potential to enhance the antifungal properties and skin delivery of the drug. Voriconazole was encapsulated into various ethosomal preparations and the effect of phospholipid and ethanol concentrations on the ethosomes properties were evaluated. The ethosomes were evaluated for drug encapsulation efficiency, particle size and morphology and antifungal efficacy. Drug permeability and deposition were tested in rat abdominal skin. Drug encapsulation efficiency of up to 46% was obtained and it increased with increasing the phospholipid concentration, whereas the opposite effect was observed for the ethanol concentration. The ethosomes had a size of 420–600 nm and negative zeta potential. The particle size of the ethosomes increased by increasing their ethanol content. The ethosomes achieved similar inhibition zones against Aspergillus flavus at a 2-fold lower drug concentration compared with drug solution in dimethyl sulfoxide. The ex vivo drug permeability through rat abdominal skin was ∼6-fold higher for the ethosomes compared with the drug hydroalcoholic solution. Similarly, the amount of drug deposited in the skin was higher for the ethosomes and was dependent on the ethanol concentration of the ethosomes. These results confirm that voriconazole ethosomal preparations are promising topical delivery systems that can enhance the drug antifungal efficacy and improve its skin delivery

Liposomal and Ethosomal Gels for the Topical Delivery of Anthralin: Preparation, Comparative Evaluation and Clinical Assessment in Psoriatic Patients

To enhance anthralin efficacy against psoriasis and reduce its notorious side effects, it was loaded into various liposomal and ethosomal preparations. The nanocarriers were characterized for drug encapsulation efficiency, size, morphology and compatibility between various components. Optimum formulations were dispersed in various gel bases and drug release kinetics were studied. Clinical efficacy and safety of liposomal and ethosomal Pluronic®F-127 gels were evaluated in patients having psoriasis (clinicaltrials.gov identifier is NCT03348462). Safety was assessed by recording various adverse events. Drug encapsulation efficiency ≥97.2% and ≥77% were obtained for liposomes and ethosomes, respectively. Particle sizes of 116 to 199 nm and 146 to 381 nm were observed for liposomes and ethosomes, respectively. Fourier-Transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the absence of interaction between anthralin and various nanocarrier components. Tested gel bases showed excellent ability to sustain drug release. At baseline, the patients had a median Psoriasis Area and Severity Index (PASI) of 3.4 for liposomes and 3.6 for ethosomes without significant difference. After treatment, mean PASI change was −68.66% and −81.84% for liposomes and ethosomes, respectively with a significant difference in favor of ethosomes. No adverse effects were detected in both groups. Anthralin ethosomes could be considered as a potential treatment of psoriasis

Spironolactone-Loaded LeciPlexes as Potential Topical Delivery Systems for Female Acne: In Vitro Appraisal and Ex Vivo Skin Permeability Studies

Spironolactone (SP), an aldosterone antagonist with anti-androgen properties, has shown promising results in the treatment of female acne. However, its systemic side effects limit its clinical benefits. This study aimed to prepare and evaluate LeciPlexes for SP topical delivery. LeciPlexes were prepared by a one-step procedure and characterized using various techniques. Optimum LeciPlex preparation was incorporated into 1% methylcellulose gel and SP permeability was tested ex vivo in Sprague-Dawley rat skin. The maximum drug encapsulation efficiency obtained was 93.6 ± 6.9% and was dependent on the drug/phospholipid and surfactant/phospholipid ratios. A zeta potential of +49.3 ± 3.5 to +57.7 ± 3.3 mV and a size of 108 ± 25.3 to 668.5 ± 120.3 nm were observed for the LeciPlexes. FT-IR and DSC studies confirmed the incorporation of SP into the LeciPlexes through hydrophobic and hydrogen bonding interactions. SP release from the LeciPlex formulations was significantly slower than from the drug suspension. Cumulative SP permeated through rat skin from LeciPlex gel was about 2-fold higher than SP control gel. Cumulative SP deposited in the stratum corneum and other skin layers from the LeciPlex gel was about 1.8- and 2.6-fold higher than SP control gel, respectively. This new SP LeciPlex formulation is a promising carrier for the treatment of female acne