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.

Surfactant modulated interaction of hydrophobically modified ethoxylated urethane (HEUR) polymers with impenetrable surfaces.

HYPOTHESIS: The presence of surfactant modulates the surface-chemistry-specific interaction of hard colloidal particles (latex) with HEUR polymers, principally through introducing a preferential solution interaction rather than a competitive surface interaction; addition of surfactant leads to a preponderance of polymer/surfactant solution complexes rather than surface-bound complexes. EXPERIMENTS: A range of model formulations comprising a hexyl end-capped urethane polymer (C6-L-(EO100-L)9-C6), sodium dodecylsulfate (SDS) and a series of polystyrene-butylacrylate latices (PS-BA-L) have been characterised in terms of rheology, particle surface area (solvent relaxation NMR), polymer conformation (small-angle neutron scattering) and solution composition to build up a detailed picture of the distribution of the HEUR in the presence of both surfactant and latex. FINDINGS: There is very weak adsorption of C6-L-(EO100-L)9-C6 to only the most hydrophobic latex surface studied, an adsorption that is further weakened by the addition of low levels of surfactant. Macroscopic changes in the hydrophobic latex system may be interpreted in terms of bridging flocculation at low polymer concentrations. No adsorption of C6-L-(EO100-L)9-C6 is observed in the case of hydrophilic surfaces. In most cases, the observed behaviour of the ternary system (polymer/surfactant/particle) is highly reminiscent of the binary (polymer/surfactant) system at the appropriate composition, suggesting that the polymer/surfactant solution interaction is the dominant one.

Probing the interaction of nanoparticles with mucin for drug delivery applications using dynamic light scattering.

Drug delivery via the eye, nose, gastrointestinal tract and lung is of great interest as they represent patient-compliant and facile methods to administer drugs. However, for a drug to reach the systemic circulation it must penetrate the "mucus barrier". An understanding of the characteristics of the mucus barrier is therefore important in the design of mucus penetrating drug delivery vehicles e.g. nanoparticles. Here, a range of nanoparticles - silica, aluminium coated silica, poly (lactic-co-glycolic acid) (PLGA) and PEGylated PLGA - each with known but different physicochemical characteristics were examined in the presence of mucin to identify those characteristics that engender nanoparticle/mucin interactions and thus, to define "design rules" for mucus penetrating (nano)particles (MPP), at least in terms of the surface characteristics of charge and hydrophilicity. Dynamic light scattering (DLS) and rheology have been used to assess the interaction between such nanoparticles and mucin. It was found that negatively charged and hydrophilic nanoparticles do not exhibit an interaction with mucin whereas positively charged and hydrophobic nanoparticles show a strong interaction. Surface grafted poly (ethylene glycol) (PEG) chains significantly reduced this interaction. This study clearly demonstrates that the established colloid science techniques of DLS and rheology are very powerful screening tools to probe nanoparticle/mucin interactions.