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With particulate systems topical CPA treatment may be an additional therapeutic option for acne and other diseases of the pilosebaceous unit.

Solid lipid nanoparticles (SLNs) can enhance drug penetration into the skin, yet the mechanism of the improved transport is not known in full. To unravel the influence of the drug-particle interaction on penetration enhancement, 3 glucocorticoids (GCs), prednisolone (PD), the diester prednicarbate (PC) and the monoester betamethasone 17-valerate (BMV), varying in structure and lipophilicity, were loaded onto SLNs. Theoretical permeability coefficients (cm/s) of the agents rank BMV (–6.38) ≧ PC (–6.57) > PD (–7.30). GC-particle interaction, drug release and skin penetration were investigated including a conventional oil-in-water cream for reference. Both with SLN and cream, PD release was clearly superior to PC release which exceeded BMV release. With the cream, the rank order did not change when studying skin penetration, and skin penetration is thus predominantly influenced by drug release. Yet, the penetration profile for the GCs loaded onto SLNs completely changed, and differences between the steroids were almost lost. Thus, SLNs influence skin penetration by an intrinsic mechanism linked to a specific interaction of the drug-carrier complex and the skin surface, which becomes possible by the lipid nature and nanosize of the carrier and appears not to be derived by testing drug release. Interestingly, PC and PD uptake from SLN even resulted in epidermal targeting. Thus, SLNs are not only able to improve skin penetration of topically applied drugs, but may also be of particular interest when specifically aiming to influence epidermal dysfunction.

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In the field of topical application without or with little systemic side-effects to reach antiinflammatory or anti-androgeneous effects, nanoparticles as carriers for drugs as betamethason-17-valerate, prednicarbate, prednisolone, RU 58841-myristate or cyproterone acetate have proven to enhance the transdermal delivery. This enhancement is closely connected to the interaction of the drug molecules with the lipid carrier systems, i.e. incorporation into the carriers or attachment to their surfaces. Whereas the techniques to measure the penetration profiles in the cutaneous region of the skin are well established in the case of fluorescence microscopy applied to thin slices of epidermis or being established in the case of multiphoton microscopy to monitor this fluorescence, the methods for the investigation of the type of interaction between drugs and carrier systems are relatively new: In the case of electron spin resonance the sample volumes have to be restricted to capillary sizes to avoid parelectric losses in the microwave cavities, in the case of the novel method of parelectric spectroscopy we are free from such restrictions. The application of the latter method will be presented here in detail concerning the underlying theory, the experimental aspects as well as the algorithms to extract the parameters of interest from the measured samples. As samples we restrict ourselves to solid lipid nanoparticles coated with different surfactants as carriers for drug-, dye-or spinlabel molecules.

Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin penetration, solid lipid nanoparticles (SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.5 ± 0.1%. For improved preclinical evaluation, we combined tissue engineering with clinically used keratin-18 quantification. Three doses of 10^-3 mol/l OxBu, dissolved in phosphate-buffered saline as well as loaded to SLN, were effective on reconstructed NMSC. Tumour response and apoptosis induction were evaluated by an increase in caspase-cleaved fragment of keratin-18, caspase-7 activation as well as by reduced expression of matrix metallopeptidase-2 and Ki-67. OxBu efficacy was superior to equimolar 5-fluorouracil solution, and thus the drug should be subjected to the next step in preclinical evaluation.