Modification of the conformational skin structure by treatment with liposomal formulations and its correlation to the penetration depth of aciclovir.

The stratum corneum (SC), top layer of the epidermis, is comprised mostly of lipids that are responsible for the permeability properties of the SC and which protect the body from external agents. Changes in these skin microconstituents can be understood by instrumental methods such as attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. The present work shows that different types of analyzed skin, dermatomed abdominal porcine skin, pig ear skin, and human heat separated skin, influenced both the shape and the intensity of recorded spectra. The typical FTIR spectral bands of the conformation of the lipid aliphatic chains in the skin samples were altered after treatment with pure DPPC liposomes and chitosan (CS) coated DPPC liposomes, but not with aqueous CS-solution. The conformational change could be the reason for the variable permeability of the skin. This was confirmed by tape stripping on pig ear skin (imitating in vivo studies): the amount of aciclovir penetrating from polymer coated and polymer free liposomes was significantly higher under the skin surface in comparison with the aqueous CS-solution. Moreover, the addition of the polymer to liposomes induced a higher skin penetration than pure liposomes. One explanation might be the CS's stronger adhesion to the skin.

Improvement in physicochemical parameters of DPPC liposomes and increase in skin permeation of aciclovir and minoxidil by the addition of cationic polymers.

1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes were prepared by high-pressure homogeniser and coated with two cationic polymers, chitosan (CS) and for the first time Eudragit EPO (EU), respectively. Compared to the control liposomes, the polymeric liposomes showed greater physicochemical stability in terms of mean particle size and zeta potential at room temperature. In the present study, aciclovir and minoxidil have been used as hydrophilic and hydrophobic candidates. In the presence of the drugs, the polymeric liposomes still showed constant particle size and zeta potential. Influences of polymers and model drugs on thermotropic phase transition of DPPC liposomes were studied by micro-differential scanning calorimetry (microDSC). The influences on configuration of DPPC liposomes were investigated by Fourier transform infrared spectroscopy (FTIR). According to DSC results, cationic polymers had a stabilising effect, whereas aciclovir and minoxidil changed the physical properties of the DPPC bilayers by influencing the main phase transition temperature and erasing the pre-transition. The investigation of CO stretching bands of DPPC at 1736 cm(-1) in FTIR spectra showed that aciclovir has strong hydrogen bonding with CO groups of DPPC, whereas carbonyl groups were free in minoxidil presence. Moreover, the coating of liposomes with CS or EU led to higher skin diffusion for both drugs. This could be explained as an effect of positively charged liposomes to interact stronger with skin negatively charged surface and their possible interactions with structures below the stratum corneum.

Analysis of skin penetration of phytosphingosine by fluorescence detection and influence of the thermotropic behaviour of DPPC liposomes.

Phytosphingosine (PS) is a promising compound in skin formulations, considering its application in the treatment of acne and different inflammations as well as in the 'anti age' cosmetics. PS, as an active substance was incorporated in DPPC liposomes intended to standard diffusion experiments, where dermatomed porcine skin was mounted in FRANZ cells. The proved skin retention was about 5.5% (w/w) after 24h and about 6.8% (w/w) after 48 h of the applied PS amount, whereas only about 0.05% (w/w) and about 0.07% (w/w) PS, respectively, could be observed in the acceptor medium. To increase analytical sensitivity PS was derivatised by o-phtalaldehyde (OPA) reagent and analysed by HPLC with fluorescence detection. The higher amount of PS within the skin symbolised an interaction with lipid structures in skin. Further evaluation of this interaction was accomplished by applying microDSC studies of PS with DPPC as a model membrane. For this purpose liposomes were prepared by increasing PS content. The characteristic endothermic peak observed for the single system was shifted to a slightly higher temperature and broadened as the mole fraction of PS increased. This might be the effect of mixing of PS with DPPC. An addition of 10 mol% PS resulted in more than double sized particles pointing to a possible change in the liposomal shape.

Chitosan-tripolyphosphate nanoparticles as a possible skin drug delivery system for aciclovir with enhanced stability.

OBJECTIVES: The aim of the present study was to create a skin delivery system based on chitosan-tripolyphosphate nanoparticles for aciclovir with enhanced chemical stability. METHODS: Nanoparticles were formed spontaneously using ionotropic gelation with tripolyphosphate. Two different sizes of aciclovir-loaded nanoparticles were characterised in terms of zeta potential, particle size and polydispersity index. KEY FINDINGS: Standard diffusion experiments using Franz-type diffusion cells showed reasonable skin permeability that depended on particle size and chitosan content. The larger the nanoparticle, having a higher chitosan content, the better the aciclovir permeation through porcine skin. Differential scanning calorimetry studies showed a remarkable decrease in the typical transition temperature, indicating an interaction between skin lipid bilayer and the nanoparticles. Moreover, the chemical stability of aciclovir was significantly increased by the nanoparticle system. After the observation period of 5 weeks, aciclovir incorporated into nanoparticles had undergone photo-oxidation to a significantly lower extent than pure aqueous solution. This degradation product of aciclovir was analysed using LC/MS, and its identity established. CONCLUSIONS: These studies demonstrate that incorporation of aciclovir into chitosan-tripolyphosphate nanoparticles significantly improves its chemical stability. Moreover, skin diffusion studies in vitro showed improved permeation of aciclovir from the nanoparticle system, especially from nanoparticles with higher chitosan content.

Chitosan-glycolic acid: a possible matrix for progesterone delivery into skin.

BACKGROUND: Chitosan-EDTA is an interesting matrix for dermal delivery; however, the adhesiveness is too small. Therefore, the purpose of this study was to investigate chitosan-glycolic acid as possible dermal matrix for progesterone in comparison to chitosan-EDTA and carrageenan. METHOD: After preparation of the chitosan-glycolic acid salt and characterization by NMR and FTIR, tensile studies using porcine skin and rheology measurements as well as standard diffusion experiments using dermatomed porcine skin were performed. RESULTS: Results showed an improved skin adhesiveness of chitosan-glycolic acid and increased viscosity. Skin diffusion studies indicated the highest cumulative permeation of progesterone after 48 hours from chitosan-glycolic acid followed by carrageenan and chitosan-EDTA. A possible explanation might be a longer residence time on skin caused by the higher adhesiveness and with it higher progesterone skin permeation. CONCLUSION: Chitosan-glycolic acid can be recommended as a suitable polymer for hydrogels and an adhesive matrix for a transdermal application of progesterone exhibiting excellent skin adhesiveness and permeation properties.