Vesicular carriers containing phenylethyl resorcinol for topical delivery system; liposomes, transfersomes and invasomes

Topical administration of phenylethyl resorcinol(PR) has attracted much attention as skin lightening agent with potent anti-tyrosinase activity. Two novel types of elastic carriers were developed to overcome the limitation of PR as topical delivery by increasing the solubility, stability and decreasing skin irritation compared to conventional liposomes. In addition, it also promotes skin penetration of PR to reach deep skin layer at the target site. The lead formulations were obtained from the invasomes containing 1%(w/v) d-limonene mixed with 10%(v/v) absolute ethanol as the skin enhancer, and transfersomes containing 15%(w/w) sodium deoxycholate(SDC) as edge activator. All formulations gave a vesicle size < 500 nm, polydispersity index(PDI) < 0.3, high zeta potential, entrapment efficiency > 50%, and good stability on storage at 30 °C at 75% RH for 4 months. Transfersomes have a lower degree of deformability(6.63%) than invasomes(25.26%). In contrast, the liposomes as rigid vesicles do not show a deformable property. This characteristic affects the skin permeation, and thus, transfersomes with high elastic property provided a significantly higher cumulative amount, steady state flux( J ss) and permeability coefficient( K p) compared to other formulations. However, in vitro PR accumulation in full-thickness newborn pig skin demonstrated that the application of elastic carrier formulations gave significantly higher accumulation than liposomes, and gave anti-tyrosinase activity up to 80%. These results are straightforwardly related to the results of cellular level study. Transfersomes and invasomes showed higher tyrosinase inhibition activity and melanin content reduction when compared to liposomes in B16 melanoma cells. In addition, acute irritation test in rabbits confirmed that these formulations are safe for skin application. Therefore, elastic vesicle carriers have theefficiency to deliver PR into the deep skin in both quantity and effectiveness which are better than conventional liposomes and appropriate for a skin lightening product.

Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo

The aims of this study were to prepare novel transfersomes(TFs)for tacrolimus to treat atopic dermatitis,and to observe the therapeutic effects on mice atopic dermatitis,as compared to commercial tacrolimus ointment(Protopic
)and liposomes-gel.Different kinds of surfactantsdsodium cholate,Tween 80 and Span 80 were investigated to prepare TFs respectively.TFs-Tween 80 was selected as the optimal carrier owing to the best deformability and the highest drug retentions.Entrapment efficiency and diameter were also evaluated.The optimized TFs were further made into gel and in vitro drug release of TFs-gel after 24 h was higher than the commercial ointment.Cumulative drug release from TFs-gel after 12 h in vitro was 37.6%.The optimized TFs-gel illustrated remarkably highest drug skin retentions when compared with liposomes-gel and commercial ointment in vivo skin retention experiments.The amounts of tacrolimus in epidermis and dermis from TFsgel were 3.8 times and 4.2 times respectively as much as ointment,while liposomes-gel was only 1.7 times and 1.4 times respectively as compared to ointment.Topical application of TFs-gel displayed the best therapeutic effect on mice atopic dermatitis induced by repeated topical application of 2,4-dinitrofluorobenzene.Thus TFs displayed superior performance and effective skin target for topical delivery of tacrolimus.

Vesicular nanocarrier based treatment of skin fungal infections: Potential and emerging trends in nanoscale pharmacotherapy

Occurrence of skin fungal infections is increasing nowadays and their presence is more prominent in patients suffering from immunocompromised diseases like AIDS. Skin fungal infections are a major cause of visits by patients to dermatology clinics. Although, a large number of antifungal agents are available for treatment of skin fungal infections, but, their toxic profile and physicochemical characteristics reduce therapeutic outcome. When these antifungal agents are delivered topically using conventional formulations like creams and gels, they may cause various side effects like redness, burning, and swelling at the site of application. Therefore, various vesicular formulations(phospholipid based or non phospholipid based) have been explored by pharmaceutical scientists to treat skin fungal infections topically. Vesicular formulation explored for the purpose are liposomes, ethosomes, transfersomes, transethosomes, niosomes, spanlastics, oleic acid vesicles, and nanoparticles.These formulations show various advantages like bioavailability enhancement of bioactives,high skin permeation power, no side effects at application site, dosing frequency reduction,and sustained drug release. Therefore, in the present article, we have discussed about the utility of various vesicular nanocarrier systems to treat skin fungal infections.

Skin Retention Determination and Clinical Efficacy Evaluation of a Novel High Oil-Contained Hpr Transfersome Permeable Formulation

In order to increase the skin retention of HPR(Hydroxypinacone Retinoate),a novel high oil-contained HPR transfersome WL-HPR1130 was prepared.Conventional essence containing HPR was used as the control group,WL-HPR1130 essence was used as the experimental group,the skin retention of HPR were determined respectively.The anti-wrinkle efficacy of WL-HPR1130 essence was evaluated at the same time.The retention of HPR was 11.40μg/cm2 in the experimental group and 1.41μg/cm2 in the control group,which was 8.08 times higher than the control group.The wrinkles and fine lines were significantly reduced and smoothed after 2 and 4 weeks by experimental group sample.The average length,width and depth of wrinkles were decreased by 14.26%,18.31%,7.17%after 2 weeks,and were decreased by 29.39%,38.25%,8.60%after 4 weeks.The average length,width and depth of fine lines were decreased by 22.35%,12.60%,8.00%after 2 weeks,and were decreased by 27.10%,20.24%and 15.90%after 4 weeks,which has a significant visual changes.WLHPR1130,a novel high oil-contained HPR transfersome formulation,can significantly increase the retention of HPR in the skin.And the WL-HPR1130 essence have remarkable anti-wrinkle and smooth fine lines effects.

Vesicular drug delivery systems for oral absorption enhancement

Oral administration is the most acceptable route of drug delivery at this stage due to its convenience,safety,and non-invasiveness.However,drugs given orally are exposed to a complex gastrointestinal environment,causing a tremendous challenge for their successful absorption into the circulation.Over the past decades,researchers have developed various novel pharmaceutical technologies to improve oral absorption,among which the vesicular drug delivery system(like liposomes,niosomes and transfersomes)has received extensive attention.Encouragingly,there have been several investigations confirming the improved effect of vesicular drug delivery systems on oral drug absorption.Nevertheless,the clinical translation of oral vesicular drug delivery systems has been less impressive than implied by the positive results,and few vesicular formulations for oral use have been marketed yet.Against this background,this article provides an overview of the current applications and challenges associated with the vesicular delivery systems available for oral drug delivery,specifically liposomes,niosomes,transfersomes,chitosomes and bilosomes.The composition,formation mechanism,drug delivery advantages and application cases of these carriers in oral drug delivery are summarized.The possible mechanisms by which vesicular carriers enhance oral drug absorption are analyzed in terms of the in vivo process of oral drugs.Further,the challenges that oral vesicular carriers now face,such as safety,undefined in vivo fate,and scale-up production,are summarized,while possible strategies to deal with them are indicated.By reviewing the aforementioned,it can facilitate a more comprehensive knowledge of vesicular systems that can be used for oral drug delivery,providing a theoretical basis and reference for the design of oral formulations.

Reverse immune suppressive microenvironment in tumor draining lymph nodes to enhance anti-PD1 immunotherapy via nanovaccine complexed microneedle

The maturation of dendritic cells(DCs)and infiltration effector T cells in tumor-draining lymph node(tdLN)and tumor tissue are crucial for immunotherapy.Despite constructive progresses have been made with anti-programmed death-1(anti-PD1)checkpoint blockade for immunotherapy,the efficacy of PD1/PD-L1 therapy deserves to be improved.Here,we constructed a novel transfersomes based nanovaccine complexed microneedles to enhance anti-PD1 immunotherapy via transdermal immunization for skin tumor therapy.Transfersomes were functionalized with DCs targeting moietyαCD40,co-encapsulated with antigens and adjuvant poly I:C.Moreover,transdermal administration promoted accumulation in tumor-draining lymph nodes(tdLN),which could facilitate cellular uptake,activate DCs maturation and enhance Th1 immune responses.Using a mouse melanoma model,combined therapy of such nanovaccine complexed microneedles with pembrolizumab(αPD1)was able to enhance cytotoxic T lymphocytes activation,promote infiltration and reduce regulatory T cells frequency in tdLN and tumor tissues,which achieved reversion of the immunosuppressive microenvironment into immune activation.This study highlighted the potential of transfersomes based nanovaccines complexed microneedles as an attractive platform for tumor immunotherapy.