Utilization of response surface design for development and optimization of rosuvastatin calcium-loaded nano-squarticles for hair growth stimulating VEGF and IGF production: in-vitro and in-vivo evaluation.

INTRODUCTION: Countless individuals experience negative emotions as hair loss pattern affects their self-esteem and well-being. Rosuvastatin calcium (Ca-RUV) was reported to stimulate the growth of the hair in the applied area, hence, it was selected as a potential hair loss treatment drug. SIGNIFICANCE: This study aims to develop and optimize (Ca-RUV) loaded squarticles (SQRs) and assess their ability to deliver and release Ca-RUV in the hair follicle for the promotion of hair growth. METHODS: A response surface design was utilized to study the effect of varying Pluronic® F68 (PF68) and the percentage of liquid lipids within the core of the SQRs and the effects of particle size, entrapment efficiency, and drug released percentage after 24 h (%Q24) were assessed. The optimized formula was subjected to DSC, XRD, and in-vivo evaluation in rats. RESULTS: SQRs stabilized by 0.8% PF68 and contained 37.5% liquid lipids showed an acceptable particle size (250 nm), drug entrapment efficiency (75%), and %Q24 (100%). The in-vivo studies illustrated the ability of the formula to regrow hair in animals after 10 days due to the elevation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) to their normal values and by 9% and 54%, respectively, relative to standard therapy minoxidil (5%). CONCLUSION: Thus, it can be concluded that the optimized formula of Ca-RUV loaded SQRs showed superior in-vivo results in the promotion of hair growth in a shorter period relative to the marketed product. Therefore, the formula can offer a viable option for the treatment of hair loss.

Chondroitin Sulphate-Chitosan polyelectrolyte complexes for etorocoxib transdermal delivery: in silico, in vitro and in vivo studies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects around 1% globally leading to joint inflammation and disability. Etorocoxib (ETR) is a potent COX-2 inhibitor traditionally used orally to alleviate RA induced inflammation, yet it causes hepatic side effects on prolonged use. This study aims for in silico optimization of ETR polyelectrolyte complex (PEC) utilizing chondroitin sulphate (CS) and chitosan (CH) for transdermal delivery to RA-inflamed joints with a synergistic anti-inflammatory action owing to CS. An artificial neural network (ANN) combined with 22 factorial design was used to optimize the PEC formula according to particle size (PS) and entrapment efficiency (%EE) by varying CS and CH concentrations. The optimum ETR PEC was incorporated in a gel and examined for its in vitro release, ex vivo permeation, in vivo inflammatory biomarkers, and histopathological evaluation in rats. The optimized formula (F3) with 0.1 CH% w/w and 0.5 CS %w/w showed a PS of 214.98 ± 17.24 nm, %EE 75.31 ± 1.67%, and enhanced in vitro release profile, ex vivo permeation and in vivo anti-inflammatory effect compared to ETR gel via suppressing the expression of IL-6, TNF-α, and TGF-ß pro-inflammatory cytokines as well as the additional anti-inflammatory effect of CS. In conclusion, ETR-PEC gel holds promise as transdermal therapy for managing RA-induced inflammation.

Efficient lung-targeted delivery of risedronate sodium/vitamin D3 conjugated PAMAM-G5 dendrimers for managing osteoporosis: Pharmacodynamics, molecular pathways and metabolomics considerations.

AIMS: This study aims at formulating combined delivery of Risedronate sodium (RIS) and Vitamin D3 (VITD3) for augmented therapeutic outcome against osteoporosis (OP) using deep lung targeted PAMAM-G5-NH2 dendrimers to minimize RIS gastrointestinal side effects and enhance both drugs bioavailability through absorption from the alveoli directly to the blood. METHODS: RIS-PAMAM-G5-NH2, VITD3-PAMAM-G5-NH2, and RIS/VITD3-PAMAM-G5-NH2 were prepared and evaluated in vitro for particle size (PS), zeta potential (ZP), %loading efficiency (%LE), morphology and FTIR. The efficacy of the RIS/VITD3-PAMAM-G5-NH2 compared to oral RIS was evaluated in OP-induced rats by comparing serum calcium, phosphorus, and computed bone mineral density (BMD) pre- and post-treatment. Additionally, a comprehensive metabolomics and molecular pathways approach was applied to find serum potential biomarkers for diagnosis and to evaluate the efficacy of inhaled RIS/VITD3-PAMAM-G5-NH2. KEY FINDINGS: RIS/VITD3-PAMAM-G5-NH2 was successfully prepared with a %LE of 92.4 ± 6.7 % (RIS) and 83.2 ± 4.4 % (VIT-D3) and a PS of 252.8 ± 34.1 adequate deep lung delivery. RIS/VITD3-PAMAM-G5-NH2 inhalation therapy was able to restore serum calcium, phosphorus, and BMD close to normal levels after 21 days of treatment in OP-induced rats. The WNT-signalling pathway and changes in the metabolite levels recovered to approximately normal levels upon treatment. Moreover, histone acetylation of the WNT-1 gene and miR-148a-3p interference proved to play a role in the regulation of the WNT-signalling pathway during OP progression and treatment. SIGNIFICANCE: Pulmonary delivery of RIS/VITD3-PAMAM-G5-NH2 offers superior treatment for OP treatment compared to the oral route. Molecular and Metabolic pathways represents key indicators for OP diagnosis and progression.

Stabilizing excipients for engineered clopidogrel bisulfate procubosome derived in situ cubosomes for enhanced intestinal dissolution: Stability and bioavailability considerations.

Clopidogrel bisulfate (CB) is a golden antiplatelet treatment, yet its benefits are limited by its low bioavailability (<50%) caused by poor intestinal solubility and absorption. The present study aims to improve CB intestinal solubility and absorption through developing a novel stable dry CB procubosomes tablets ready to disintegrate and re-disperse upon dilution in the GIT forming in situ CB cubosome nanoparticles while simultaneously overcome the poor stability of conventional cubosome dispersion at room temperature. Glyceryl monooleate based CB cubosome dispersion was prepared using Poloxamer 407 as surfactant, freeze dried using different stabilizing excipients (dextrose, mannitol and avicel) then compressed into procubosome tablets. The effect of excipient's physicochemical properties on the flowability, in vitro dissolution and stability at accelerated conditions (40 ±â€¯2 °C/75 ±â€¯5% RH) were evaluated. The prepared procubosomes exhibited an excipient type dependent dissolution profile where Avicel based procubosome tablet CF2 showed the highest in vitro dissolution profile among other excipients used during the freeze drying process. Upon transition to intestinal pH of 6.8 to mimic the drug absorption site, CF2 procubosome Avicel tablet, was able to preserve the enhanced CB release profile (99.6 ±â€¯6.92%) compared to commercial Plavix® where, CB dissolved % dropped dramatically to 79.1 ±â€¯2.45%. After storage for six months, CF2 retained the fresh tablet drug content of 98.5 ±â€¯5.82% and dissolution properties. Moreover, following oral administration in rabbits, CF2 showed higher relative bioavailability (153%) compared to commercial Plavix® with significant higher Cmax,shorter tmax, as well as enhanced antiplatelet activity.