Formulation development of lipid nanoparticles: Improved lipid screening and development of tacrolimus loaded nanostructured lipid carriers (NLC).

Lipid nanoparticles are well-known nanocarriers for improved drug delivery. Their formulation development typically involves three formulations steps. In the first part a suitable lipid mixture which enables a high loading capacity and high encapsulation efficacy of the active needs to be identified (lipid screening). In the second step suitable stabilizers that enable the production of small-sized lipid nanoparticles with narrow size distribution and sufficient physical stability need to be identified (stabilizer screening, optimization of production parameters) and in the third step the biopharmaceutical efficacy needs to be evaluated. Based on the results obtained the formulations will require further optimization. The classical formulation development of lipid nanoparticles and especially the classical lipid screening is tedious. Therefore, in this study, a novel approach for the lipid screening that was based on the determination of the Hansen solubility parameters was evaluated and the results obtained were compared to the results from the classical model. Tacrolimus was used as a model drug. Results showed that both lipid screenings led to similar results, indicating that the new approach can be used for future developments. The optimized formulation was composed of a lipid matrix system that contained waxes, triglycerides and monoacylglycerols with various carbon chain lengths (C8, C10, C16, C18) and enabled an encapsulation efficiency of ~99%. The stabilizer screening showed that surfactants with high HLB values, lower molecular weight, and shorter alkyl chain length tended to form smaller particles with narrower size distribution and better physical stability. The most suitable surfactant was found to be a caprylyl/capryl glucoside (Plantacare® 810), a PEG-free stabilizer, that is extremely mild for atopic skin. It led to particle sizes of about 200 nm and a zeta potential well above |30| mV. The optimized formulation contained 0.1% tacrolimus and possessed good physical stability. In conclusion, an optimized method for the selection of lipids that results in a limited number of experiments could be established and tacrolimus loaded lipid nanoparticles with similar drug load as a marketed formulation was successfully developed in this study.

Segmental vitiligo: a randomized controlled trial to evaluate efficacy and safety of 0.1% tacrolimus ointment vs 0.05% fluticasone propionate cream.

BACKGROUND: Segmental vitiligo is a small subset of vitiligo which responds very well to surgical therapy, but the role of medical treatment is not very well defined. AIM: To compare the efficacy and safety of 0.1% tacrolimus ointment versus 0.05% fluticasone propionate cream in patients of segmental vitiligo. METHODS: A randomized control trial was conducted in a tertiary care hospital on 60 consecutive patients with segmental vitiligo. Patients with segmental vitiligo exclusively or along with focal vitiligo, untreated or had not taken any topical treatment in previous 1 month or systemic treatment in previous 2 months, from May 2005 to January 2007, were block randomized into two groups. Children <5 years, pregnant and lactating women, and patients with known hypersensitivity to either drug and with associated multiple lesions of vitiligo were excluded. Group A (n = 29) patients were treated with tacrolimus 0.1% ointment twice daily and group B (n = 31) patients were treated with 0.05% of fluticasone cream once daily for 6 months. Response and side effects were recorded clinically and by photographic comparison. RESULTS: Nineteen patients treated with tacrolimus and 21 patients treated with fluticasone completed the treatment with median repigmentation of 15% and 5%, respectively, at 6 months (P = 0.38). Transient side effects limited to the application site were observed. CONCLUSIONS: Both tacrolimus and fluticasone propionate produce variable but overall unsatisfactory repigmentation in segmental vitiligo.

Type 1 leprosy reversal reaction treated with topical tacrolimus along with systemic corticosteroids.

An 11-year-old black Haitian boy presented with borderline lepromatous leprosy and was treated with rifampicin, dapsone, and clofazimine. After 4 months he developed a severe type 1 reversal reaction without nerve involvement. He was started on prednisolone (1 mg/kg daily). After 4 weeks of treatment with corticosteroids, his condition did not improve and the lesions remained painful. The patient was given a therapeutic trial with twice daily application of topical tacrolimus 0.1% ointment. The result was a dramatic improvement in the skin lesions. The patient's condition was maintained by topical tacrolimus therapy, with healing of all skin lesions. The prednisolone dose was then tapered to zero over a period of 12 weeks. To the best of our knowledge, this is the first report of the efficacy of topical tacrolimus in the treatment of type 1 leprosy reaction.