Co-loading of finasteride and baicalin in phospholipid vesicles tailored for the treatment of hair disorders.

Hair loss affects a large number of people worldwide and it has a negative impact on the quality of life. Despite the availability of different drugs for the treatment of hair disorders, therapeutic options are still limited and scarcely effective. An innovative strategy to improve the efficacy of alopecia treatment is presented in this work. Finasteride, the only oral synthetic drug approved by Unites States Federal Drug Administration, was loaded in phospholipid vesicles. In addition, baicalin was co-loaded as an adjuvant. Their effect on hair growth was evaluated in vitro and in vivo. Liposomes, hyalurosomes, glycerosomes and glycerol-hyalurosomes were manufactured by using a simple method that avoids the use of organic solvents. All the vesicles were small in size (∼100 nm), homogeneously dispersed (polydispersity index ≤0.27) and negatively charged (∼-16 mV). The formulations were able to stimulate the proliferation of human dermal papilla cells, which are widely used in hair physiology studies. The analysis of hair growth and hair follicles of C57BL/6 mice, treated with the formulations for 21 days, underlined the ability of the vesicles to improve hair growth by the simultaneous follicular delivery of finasteride and baicalin. Therefore, the developed nanosystems can represent a promising tool to ensure the efficacy of the local treatment of hair loss.

Development of antibiotic loaded biodegradable matrices to prevent superficial infections associated to total knee arthroplasty.

Development of a pharmaceutical form for the superficial infections related with arthroplasties would be helpful for clinical practice. In this context, we set out to evaluate ciprofloxacin and gentamicin elution from systems based on chitosan. Films and semisolid hydrogels containing chitosan alone (2%) or in combination with gelatin (6%) or different proportions (from 12% to 36%) of tetrakis-(hydroxymethyl)-phosphonium-chloride (THPC) were tested as delivery systems. Different antibiotic doses were assayed (0.5 mg/cm2,1 mg/cm2 and 2 mg/cm2). Antibiotic release was studied for each formulation. In vitro cytocompatibility studies and a simulation exercise for bioactivity evaluation were performed. Samples containing chitosan or chitosan-gelatin released the antibiotics at very high rates. On the contrary, ciprofloxacin released was kept for 6 days from THPC-chitosan films and hydrogels. From hydrogel formulations release could be changed by varying the percentage of THPC. The system containing 12%-THPC-chitosan with 2 mg/cm2 of ciprofloxacin showed that 100% of patient would be covered during 72 h post-surgery. The concentration of 12%-THPC did not show cytotoxicity in NIH3T3 mouse fibroblasts after 48 h. THPC is suitable as crosslinker for chitosan when ciprofloxacin is incorporated showing a sustained release during 6 days.

Sorbitol-penetration enhancer containing vesicles loaded with baicalin for the protection and regeneration of skin injured by oxidative stress and UV radiation.

Aiming at improving the protective effects of baicalin on the skin, new highly-biocompatible penetration enhancer containing vesicles (PEVs) were developed by modifying the base formulation of transfersomes with sorbitol, thus obtaining sorbitol-PEVs. An extensive evaluation of the physico-chemical features of both transfersomes and sorbitol-PEVs was carried out. Transfersomes were mainly close-packed, multi-compartment vesicles, while sorbitol-PEVs appeared mostly as single, spherical, unilamellar vesicles. All the vesicles were small in size (∼128 nm) and negatively charged (∼-67 mV), without significant differences between the formulations. The in vitro delivery of baicalin to intact skin showed an improved ability of sorbitol-PEVs to favour the deposition of the flavonoid into the whole skin. In addition, the vesicular formulations protected keratinocytes and fibroblasts from oxidative stress and UV radiation, and promoted cell proliferation and migration, which favoured the closure of skin wound. Cell uptake was promoted as well, especially when sorbitol-PEVs were used.

Baicalin and berberine ultradeformable vesicles as potential adjuvant in vitiligo therapy.

0.5-1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distribution, surface charge and entrapment efficiency were assessed. The ability of the vesicles to promote the permeation of the polyphenols was evaluated. The antioxidant and photoprotective effects were investigated in vitro using keratinocytes and fibroblasts. Further, the stimulation of melanin production and tyrosinase activity in melanocytes after treatment with the vesicles were assessed. Ultradeformable vesicles were small in size, homogeneously dispersed, and negatively charged. They were able to incorporate high amounts of baicalin and berberine, and promote their skin permeation. In fact, the polyphenols concentration in the epidermis was higher than 10%, which could be indicative of the formation of a depot in the epidermis. The vesicles showed remarkable antioxidant and photoprotective capabilities, presumably correlated with the stimulation of melanin production and tyrosinase activity. In conclusion, baicalin or berberine ultradeformable vesicles, and particularly their combination, may represent promising nanosystem-based adjuvants for the treatment of vitiligo symptoms.

A novel ultradeformable liposomes of Naringin for anti-inflammatory therapy.

Ultradeformable liposomes were formulated using naringin (NA), a flavanone glycoside, at different concentrations (3, 6 and 9mg/mL). Nanovesicles were small size (∼100nm), regardless of the NA concentration used, and monodisperse (PI<0.30). All formulations showed a high entrapment efficiency (∼88%) and a highly negative zeta potential (around -30mV). The selected formulations were highly biocompatible as confirmed by in vitro studies using 3T3 fibroblasts. In vitro assay showed that the amounts (%) of NA accumulated in the epidermis (∼10%) could explain the anti-inflammatory properties of ultradeformable liposomes. In vivo studies confirmed the higher effectiveness of ultradeformable liposomes respect to betamethasone cream and NA dispersion in reducing skin inflammation in mice. Overall, it can conclude that NA ultradeformable liposomes can be considered as a promising formulation for the treatment of skin inflammatory diseases.

Nanodesign of new self-assembling core-shell gellan-transfersomes loading baicalin and in vivo evaluation of repair response in skin.

Gellan nanohydrogel and phospholipid vesicles were combined to incorporate baicalin in new self-assembling core-shell gellan-transfersomes obtained by an easy, scalable method. The vesicles were small in size (~107 nm) and monodispersed (P.I. ≤ 0.24), forming a viscous system (~24 mPa/s) as compared to transfersomes (~1.6 mPa/s), as confirmed by rheological studies. Gellan was anchored to the bilayer domains through cholesterol, and the polymer chains were distributed onto the outer surface of the bilayer, thus forming a core-shell structure, as suggested by SAXS analyses. The optimal carrier ability of core-shell gellan-transfersomes was established by the high deposition of baicalin in the skin (~11% in the whole skin), especially in the deeper tissue (~8% in the dermis). Moreover, their ability to improve baicalin efficacy in anti-inflammatory and skin repair tests was confirmed in vivo in mice, providing the complete skin restoration and inhibiting all the studied inflammatory markers.

Inhibition of skin inflammation by baicalin ultradeformable vesicles.

The topical efficacy of baicalin, a natural flavonoid isolated from Scutellaria baicalensis Georgi, which has several beneficial properties, such as antioxidative, antiviral, anti-inflammatory and antiproliferative, is hindered by its poor aqueous solubility and low skin permeability. Therefore, its incorporation into appropriate phospholipid vesicles could be a useful tool to improve its local activity. To this purpose, baicalin at increasing concentrations up to saturation, was incorporated in ultradeformable vesicles, which were small in size (∼67nm), monodispersed (PI<0.19) and biocompatible, regardless of the concentration of baicalin, as confirmed by in vitro studies using fibroblasts. On the other hand, transdermal flux through human epidermis was concentration dependent. The in vivo results showed the significant anti-inflammatory activity of baicalin loaded nanovesicles irrespective of the concentration used, as they were able to reduce the skin damage induced by the phorbol ester (TPA) application, even in comparison with dexamethasone, a synthetic drug with anti-inflammatory properties. Overall results indicate that ultradeformable vesicles are promising nanosystems for the improvement of cutaneous delivery of baicalin in the treatment of skin inflammation.