Preparation, characterization, and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis.

Cyclosporine (CYC), a calcineurin inhibitor acts specifically on T-cells and is one of the most effective treatment options for psoriasis. Systemic administration of the drug has been associated with dose-dependent toxic effects, while its topical delivery is a challenging task due to unfavourable physicochemical properties of drug. The aim of the present study is to develop and evaluate the efficacy of topical liposomal gel containing CYC loaded cationic liposomal nanocarriers in imiquimod induced psoriatic plaque model. Liposomes composed of DOTAP and cholesterol was formulated by different liposomal preparation techniques. Optimized liposomal carriers prepared by ethanol injection method were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Cationic liposomes with particle size of 111 ± 1.62 nm, PDI of 0.27 ± 0.08, entrapment efficiency of 93 ± 2.12%, and zeta potential of 41.12 ± 3.56 mV were obtained. Drug loaded liposomal gels showed shear thinning behaviour, which is suitable for topical application. Topical application of CYC liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumour necrosis factor-α, IL-17, and IL-22. In conclusion, the developed liposomal carrier of CYC was found to be effective and can find application in treatment of psoriasis.

Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis.

Thymoquinone (TMQ) is reported with good anti-psoriatic activity; however, the hydrophobicity, poor aqueous solubility, light and pH sensitive nature of TMQ hinder its delivery to target site. To address these delivery challenges of TMQ, lipospheres were explored. The topical use of lipospheres offers an effective mean of penetration along with stability and scalability. TMQ lipospheres of particle size below 70 nm were prepared and evaluated. These lipospheres resulted in deeper skin penetration, slow release and skin compatibility. Anti-inflammatory and anti-psoriatic potential of lipospheres was determined using in vitro cell lines and imiquimod induced psoriatic plaque model. Cell lines studies indicated reduction in the level of nitric oxide and IL-2, IL-6, IL-1ß, TNF-α, whereas in vivo results indicated improvement in the phenotypic, histopathological features and reduced level of IL-17 and TNF-α in psoriatic skin. These results suggest the potential of TMQ lipospheres in the management of psoriasis.

Nanocrystal-based gel of apremilast ameliorates imiquimod-induced psoriasis by suppressing inflammatory responses.

Apremilast is 'difficult-to-deliver' in stratum corneum and viable layers (viable epidermis, dermis) owing to its modest lipophilicity and poor aqueous solubility, respectively. The objective of the present research was to develop apremilast nanocrystal-based gel for enhanced anti-psoriatic efficacy for the treatment of psoriasis. Nanosuspension was generated by wet media milling with a mean particle size of 200 nm. In-vivoefficacy of nanocrystal-based gels was evaluated in the imiquimod-induced psoriatic plaque model. Nanocrystal-based gel (1% and 3% w/w) improved phenotypic, histopathological features of psoriatic skin and attenuated splenic hypertrophy, psoriasis area severity scoring. Enzyme-linked immunosorbent assay was performed to evaluate levels of psoriatic biochemical markers indicating a significant decrease in the concentration of cytokines such as IL-23, IL-17A, IL-6 and TNF-α by nanocrystal-based gels (1% and 3% w/w) over disease induced group. Skin irritation study revealed that nanocrystal-based gel was significantly less irritating than the positive control. These results suggest that nanocrystal-based gel of apremilast can be an effective strategy for the management of psoriasis.

Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis.

Psoralen in combination with ultraviolet A radiation (PUVA) is an FDA recommended therapy for clinical application in the management of severe recalcitrant psoriasis. Psoralen acts by intercalation of DNA and upon exposure to UV-A, it forms monoadducts which in turn induce apoptosis. Poor skin deposition, weak percutaneous permeability of psoralen and adverse effects of severe burning, blisters, pigmentation associated with conventional topical psoralen vehicles hinders the therapeutic efficacy and safety of topical PUVA. The aim of the present study is to formulate psoralen loaded liposomal nanocarriers for enhanced skin penetration, safety and efficacy of topical PUVA in psoriasis. Two different liposomal compositions i.e., cationic liposomes composed of DC-Chol, cholesterol and anionic liposomes composed of egg lecithin, cholesterol, tetramyristoyl cardiolipin were prepared for the topical delivery of psoralen. Liposomal carriers were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Both liposomes were prepared with particle size of nearly 100nm. Zeta potential and entrapment efficiency of cationic liposomes were +25.8mV, 75.12% and anionic liposomes were -28.5mV, 60.08% respectively. Liposomal dermal distribution demonstrated higher penetration of both liposomal carriers over solution. Similarly, skin permeation study indicated 5 fold increase in permeation of psoralen with liposomal carriers. Topical application of psoralen liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumor necrosis factor-α, IL-17 and IL-22. In conclusion, the developed liposomal carriers of psoralen were found to be promising and can find application for optimal safety and efficacy of topical PUVA in psoriasis.

Tacrolimus and curcumin co-loaded liposphere gel: Synergistic combination towards management of psoriasis.

Psoriasis is an autoimmune skin disorder characterized by hyper proliferation and poor differentiation of keratinocytes. It significantly affects patient's quality of life. This study reports the anti-psoriatic efficacy of tacrolimus and curcumin loaded liposphere gel formulation. Poor solubility, poor skin penetration and erratic absorption are some problems associated with the topical delivery of these drugs. To overcome these problems, lipospheres containing combination of tacrolimus and curcumin was prepared with a particle size of nearly 50nm and incorporated into a gel for topical application. Liposphere gel showed slow release of both the drugs and shear thinning behaviour that is desirable property of topical formulation. Further, dermal distribution study using dye loaded formulation suggested penetration of dye into skin layers. The therapeutic efficacy of tacrolimus and curcumin loaded liposphere gel was assessed on imiquimod induced psoriatic plaque model, and the level of expression of psoriatic biochemical markers was evaluated using enzyme-linked immunosorbent assay. Results indicated improvement in the phenotypic and histopathological features of psoriatic skin treated with tacrolimus and curcumin loaded liposphere gel. There was reduction in the level of TNF-α, IL-17 and IL-22 compared to imiquimod group. These results corroborate the premise that liposphere gel containing combination of tacrolimus and curcumin can be an effective strategy for the treatment of psoriasis.