Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis.

In the present study, tissue distribution and the therapeutic effect of topically applied cyclosporine A (CsA)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly(lactic acid) (mPEGhexPLA) nanocarriers (ApidSOL) on experimental autoimmune uveitis (EAU) were investigated. The CsA-loaded mPEGhexPLA nanocarrier was tolerated well locally and showed no signs of immediate toxicity after repeated topical application in mice with EAU. Upon unilateral CsA treatment, CsA accumulated predominantly in the corneal and sclera-choroidal tissue of the treated eye and in lymph nodes (LN). This regimen reduced EAU severity in treated eyes compared to PBS-treated controls. This improvement was accompanied by reduced T-cell count, T-cell proliferation, and IL-2 secretion of cells from ipsilateral LN. In conclusion, topical treatment with CsA-loaded mPEGhexPLA nanocarriers significantly improves the outcome of EAU.

Self-assembling polymeric nanocarriers to target inflammatory lesions in ulcerative colitis.

We have developed a self-assembling polymeric nanocarrier to deliver the potent immunosuppressive drug Cyclosporine A (CsA) to inflammatory lesions in ulcerative colitis (UC) patients. Our nanocarrier has a high drug loading capacity and efficiently targets its CsA payload to the diseased tissue after local administration. Tissue drug levels were several orders of magnitude higher in animals suffering from a trinitrobenzene-sulfonic acid (TNBS) - induced colitis, compared to healthy control animals; no drug was detectable in the plasma, underlining the localized delivery strategy. An efficient reduction in inflammation score was obtained with a CsA dose of 1mg/mL. Therapeutic efficacy was comparable to 5-aminosalicylic acid (5-ASA), the positive control treatment in the TNBS-induced colitis model. Repetitive treatment of healthy animals with CsA nanocarriers for seven days was well tolerated with no alterations in colon histology.

Improved topical delivery of tacrolimus: A novel composite hydrogel formulation for the treatment of psoriasis.

We have developed a composite hydrogel for improved topical delivery of the poorly soluble drug Tacrolimus (TAC) to psoriasis lesions. TAC is efficiently solubilized in methoxy poly- (ethylene glycol) hexyl substituted poly-(lactic acid) (mPEGhexPLA) based nanocarriers. For convenient and patient-friendly topical administration, TAC loaded polymeric nanocarriers were incorporated in a Carbopol® based hydrogel, to yield a composite hydrogel formulation (TAC composite hydrogel). TAC composite hydrogel was designed to have superior pharmaceutical formulation properties, delivery efficiency and local bioavailability, compared to currently available paraffin-based TAC ointments. Composite hydrogel formulations had good local tolerance and showed no signs of immediate toxicity after repeated topical administration in healthy mice. Skin delivery of TAC composite hydrogel in an imiquimod-induced psoriasis mouse model was found to be twice as high as for the commercial formulation Protopic™, used as benchmark. TAC composite hydrogel showed significant improvement in the in vivo and histopathological features of the imiquimod-induced psoriasis model.