Percutaneous absorption of benzophenone-3 loaded lipid nanoparticles and polymeric nanocapsules: A comparative study.

For the last years, the increase of the number of skin cancer cases led to a growing awareness of the need of skin protection against ultraviolet (UV) radiations. Chemical UV filters are widely used into sunscreen formulations as benzophenone-3 (BP-3), a usually used broad spectrum chemical UV filter that has been shown to exercise undesirable effects after topical application. Innovative sunscreen formulations are thus necessary to provide more safety to users. Lipid carriers seem to be a good alternative to formulate chemical UV filters reducing their skin penetration while maintaining good photo-protective abilities. The aim of this work was to compare percutaneous absorption and cutaneous bioavailability of BP-3 loaded into solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanostructured polymeric lipid carriers (NPLC) and nanocapsules (NC). Particle size, zeta potential and in vitro sun protection factor (SPF) of nanoparticle suspensions were also investigated. Results showed that polymeric lipid carriers, comprising NPLC and NC, significantly reduced BP-3 skin permeation while exhibiting the highest SPF. This study confirms the interesting potential of NPLC and NC to formulate chemical UV filters.

Aqueous dispersions of organogel nanoparticles - potential systems for cosmetic and dermo-cosmetic applications.

OBJECTIVE: The preparation and physicochemical characterization of organogel nanoparticles dispersed in water have been developed. These systems could be employed as nanocarrier for cosmetic applications or as hydrophobic reservoirs for drug delivery. METHODS: Gelled particles of organic liquid and 12-hydroxystearic acid (organogelator) were obtained by hot emulsification (T>Tgel), with a surfactant (acetylated glycol stearate) and polymers (sodium hyaluronate and polyvinyl alcohol) as stabilizing agents, and cooling at room temperature (T

Ex vivo absorption of promestriene from oil-in-water emulsion into infant foreskin.

Hypospadias is a birth defect in which the urinary tract opening is not at the tip of the penis. Hypospadias surgery is frequently complicated by healing deficiencies. Topical treatments with oestrogens were reported to improve healing. In the present study, ex vivo percutaneous absorption of promestriene, a synthetic oestrogen resulting of the double esterification of estradiol was conducted as a pre-requisite for further clinical trial in infants. Penetration of promestriene into infant foreskin treated with commercial oil in water emulsion (10 µg mg(-1)) for 24 h was characterized showing controlled release properties enabling epidermal concentration more than six times higher than dermal concentration (4.13±2.46 mg g(-1) versus 0.62±0.84 mg g(-1), respectively). Furthermore, apparent promestriene fluxes into and through the skin (i.e., 1.5 µg cm(-2) h(-1) and<0.89 µg cm(-2) h(-1), respectively) were calculated from (i) drug amount retained into epidermis and dermis, or (ii) the limit of detection into the receptor fluid. In conclusion, less than 2% of initial dose were absorbed within 24h which compared well with others steroids applied topically in colloidal systems.

Impact of intravenous lipid emulsion infusion on the stratum corneum barrier function in patients receiving parenteral nutrition.

The importance of the lipid matrix of stratum corneum (SC) in epidermal barrier function is well documented. Intravenous lipid emulsions (ILE) provide essential fatty acids (EFAs), main components of the SC lipid matrix. The objective of this study was to investigate the influence of ILE upon SC barrier function. The skin barrier was assessed by measuring transepidermal water loss (TEWL). Patients receiving lipid-containing parenteral nutrition (LCPN) were compared to patients receiving lipid-free PN (LFPN). In addition, a before/after LCPN introduction study was set up to limit the influence of inter-individual variability. Twenty-six patients receiving LCPN and seven patients receiving LFPN were included. Median age was not significantly different between the two groups. The TEWL of the LCPN group (9.05 g/m2/h) was significantly lower than the TEWL of the LFPN group (12.1 g/m2/h; Wilcoxon test: p = 0.016). The relative variation of TEWL before and after ILE treatment of 5 studied patients was 21.29 ± 10.28 %. ILE improve epidermal barrier function when compared to lipid-free parenteral treatments. Results of the before/after study confirm this conclusion and the usefulness of ILE intake for preventing excessive TEWL. SC barrier function improvement could be a choice criterion between the different ILE generations, in particular in burn patients and premature neonates.

Commonly used UV filter toxicity on biological functions: review of last decade studies.

Sunscreens provide broad-spectrum UV skin protection and contain more often UV filter combinations. Their efficacy reducing skin photo carcinogenesis and photo ageing is widely documented. However, there are many concerns about UV filter safety. Organic UV filters were the first targeted by scientist concerns, as they were showed to trigger skin allergic reactions. Inorganic UV filters were then at the heart of scientist debate especially because of their nanometric size. Over the last years, many studies have been published tending to highlight that organic as well as inorganic UV filters could lead to variable side effects after sunscreen application. However, these studies are still very controversial due to different experimental conditions and models. This review reveals that complementary studies using standardized methods are mandatory before ascertaining that UV filters threaten human health.

Assessment of sodium hyaluronate gel as vehicle for intracameral delivery of cefuroxime in endophthalmitis prophylaxis.

Sodium cefuroxime is a second-generation cephalosporin widely used at 10mg/mL for endophthalmitis prophylaxis after cataract surgery. Sodium cefuroxime solution is usually conditioned in pre-filled syringes then frozen for storage. In the present study, 0.2% sodium hyaluronate gel, natural extracellular polymer used in wound healing, was compared to conventional saline solution (0.9% sodium chloride) as drug delivery systems for cefuroxime loading in pre-filled syringes. Therefore, the temperature (4 and 25 degrees C) and time of storage (up to 21 days) varied in order to appreciate both cefuroxime and vehicle stability. Furthermore, the kinetics of drug release from both hyaluronate gel and saline solution were compared since in vitro sets of dialysis experiments. Results indicated that cefuroxime loaded in either saline solution or hyaluronate hydrogel was found stable in pre-filled syringes stored at 4 degrees C for 21 days, whereas cefuroxime degradations products appeared from the 2nd day of storage at 25 degrees C. Both drug delivery systems were found bioequivalent, although statistically slower cefuroxime dialysis was evidenced by using sodium hyaluronate vehicle. Noteworthy, cefuroxime concentration in drug delivery systems during dialysis experiment remained greater than the minimum inhibitory concentrations reported for resistant strains. In conclusion, the present stability and release study confirmed that sodium hyaluronate hydrogel is a promising vehicle for cefuroxime intracameral delivery in endophthalmitis prophylaxis.

Simultaneous characterization of oxygen transport into and through porcine skin exposed to oxygen-saturated water.

Oxygen delivery to the skin is a promising approach for treatment of dermatological diseases (e.g. ischemic wound healing). However, characterization of oxygen transport into and through the skin exposed to oxygen carrier formulations has not been reported. In the present study, we developed an original lab-made static diffusion cell mounted with porcine skin enabling the assessment of oxygen uptake into the skin (i.e., oxygen penetration) and passage through the skin (i.e., oxygen permeation). Oxygen penetration and permeation were recorded by using an optical probe implanted into the skin tissue and a Clark-type electrode plunged into the receptor solution of the diffusion cells. Permeability parameters (i.e., maximal and steady-state flux; permeability coefficient) of oxygen were determined after a 2-hour application of oxygen-saturated water to either the skin surface (exogenous delivery) or the dermis (endogenous delivery). Similar experiments were performed by using intact or stripped skin in order to appreciate the role of the stratum corneum as oxygen barrier. Exogenous delivery of oxygen to skin tissue was found more effective than endogenous delivery through intact and stripped skin. However, exogenous oxygen permeation was found smaller than that determined from endogenous delivery. The upper layers of the skin would constitute a potential oxygen reservoir created by the high solubility of oxygen in epidermal lipids. Therefore, oxygen carrier formulations might significantly improve the oxygen status in the skin for further biological effects.

Characterization of rabbit ear skin as a skin model for in vitro transdermal permeation experiments: histology, lipid composition and permeability.

AIM: The aim of this work was to characterize rabbit ear skin in view of its use in transdermal permeation experiments. METHOD: The characterization included histological analysis of the tissue, qualitative and quantitative analysis of stratum corneum (SC) lipids, differential scanning calorimetry and permeation experiments (caffeine, nicotinamide, progesterone). As a reference, pig ear skin was used. RESULTS: The results obtained show that rabbit ear skin has a similar SC thickness compared to pig skin although the viable epidermis has a different structure. The lipid composition of rabbit SC was similar to pig SC but was characterized by a lower content of ceramides and a higher content of cholesterol esters and triglycerides. In terms of permeability, rabbit ear skin was 4-7 times less permeable to hydrophilic compounds, probably because of the higher lipophilicity of its SC. The permeability to progesterone was comparable between isolated pig epidermis and rabbit ear skin. CONCLUSION: Overall, the results obtained in this work support the usefulness of rabbit ear skin as barrier for skin penetration studies, for both lipophilic and hydrophilic permeants.

Gastroretentive dosage forms: overview and special case of Helicobacter pylori.

The challenge to develop efficient gastroretentive dosage forms began about 20 years ago, following the discovery of Helicobacter pylori by Warren and Marshall. In order to understand the real difficulty of increasing the gastric residence time of a dosage form, we have first summarized the important physiologic parameters, which act upon the gastric residence time. Afterwards, we have reviewed the different drug delivery systems designed until now, i.e. high-density, intragastric floating, expandable, superporous hydrogel, mucoadhesive and magnetic systems. Finally, we have focused on gastroretentive dosage forms especially designed against H. pylori, including specific targeting systems against this bacterium.

Discriminant analysis as a tool to identify compounds with potential as transdermal enhancers.

Structure-activity relationships were sought for 73 enhancers of hydrocortisone permeation from propylene glycol across hairless mouse skin. Enhancers had chain lengths (CC) from 0 to 16 carbon atoms, 1 to 8 H-bonding atoms (HB), molecular weight 60 to 450, log P (calculated) -1.7 to 9.7 and log S (calculated) -7.8 to 0.7. These predictive properties were chosen because of their ready availability. Enhancement ratio (ER) was defined as hydrocortisone transferred after 24 h relative to control. Values for the ER ranged from 0.2 to 25.3. Multiple regression analysis failed to predict activity; ER values for the 'good' enhancers (ER > 10) were underestimated. Simple guidelines suggested that high ER was associated with CC > 12 and HB 2-5. This was refined by multivariate analysis to identify significant predictors. Discriminant analysis using CC, HB, and molecular weight correctly assigned 11 of the 12 'good' enhancers (92%). The incorrectly assigned compound was a known, idiosyncratic Br compound. Seventeen of the 61 'poor' enhancers (28%) were incorrectly assigned but four could be considered marginal (ER > 8). The success of this simple approach in identifying potent enhancers suggested its potential in predicting novel enhancer activity.

Characterization of transport of chlorhexidine-loaded nanocapsules through hairless and wistar rat skin.

Nanocapsules appear a promising approach as a drug system for topical application. However, the transport mechanism of nanocapsule-associated drug through the skin is still being questioned. In the present study, the transport of chlorhexidine-loaded poly(epsilon-caprolactone) nanocapsules through full-thickness and stripped hairless rat skin was investigated in static-diffusion cell. The chlorhexidine permeation profiles fitting the Fickian diffusion model showed that the drug encapsulation reduced the percutaneous drug absorption through stripped skin. Possible nanocapsule transport within skin conducts was suggested from the analysis of permeation parameters and confirmed by confocal laser microscopy studies. Furthermore, the chlorhexidine permeation and drug release data were highly correlated, suggesting that the magnitude of percutaneous absorption was controlled by the diffusion across the polymeric carrier. The behavior of nanocapsules at the skin interface was investigated by contact angle and surface tension measurements. The small 'wetting' of the nanocapsule on the stratum corneum surface preserved the mechanical integrity of the carrier characterized by a high specific surface at the skin interface. The flexibility of the nanocapsules assured a satisfying bioadhesion to the skin, whereas the rigidity of the carrier limited the molecular 'spill' into the skin and controlled the drug delivery to the skin.

Kinetics of chlorhexidine on intact skin following a single application.

Residual chlorhexidine concentrations were measured after application of a single dose on the skin of 22 healthy volunteers. Dosage by high-pressure liquid chromatography in the skin cleansers revealed that the residual concentrations were higher than chlorhexidine MICs for most organisms of the resident skin flora and some responsible for hand-borne infections, even 24 h after application.

[Determination of an intrinsic value of diffusion coefficient of active principle in polymeric matrix for the formulation of a controlled release system]. / Détermination d'une valeur intrinsèque du coefficient de diffusion d'un principe actif dans une matrice polymérique en vue de la formulation d'un système à libération contrôlée.

The study of diffusion in a polymeric system often poses difficult experimental problems, notably when the rate of release is determined in a liquid receptor phase which can interact with the system. In this publication, we propose two experimental methods to determine the diffusion coefficient by a gel-gel kinetic release study, in which the receptor is a same gel unloaded initially. The first method is based on the use of radioactive tracers and a multi-channel radioactivity counter to obtain, at different times, the concentration profiles in the diffusion medium. The theoretical model is given for a gel donor with the concentration C0 of diffusing molecules is below or above the solubility Cs. The second method is based on the measurement of the displacement of solubility front during the diffusion within the system in the case C0 > Cs. The theoretical model shows that this displacement is a function of square root of t. For illustration, two experimental determinations of testosterone diffusion coefficient on the one hand in a silisic acid gels and on the other hand in an acrylic acid gels are given.