What About the Rheological Properties of PRP/Microfat Mixtures in Fat Grafting Procedure?

BACKGROUND: Fat grafting has emerged as a reference procedure in daily plastic surgery practice. Unpredictable fat resorption is the main clinical problem. For this purpose, the addition of PRP to enhance fat revascularization is now an easy and popular procedure. However, no consensus exists regarding the respective volume of fat and PRP used to obtain the ideal mixture. This study investigated the rheological properties of microfat mixed with different proportions of PRP. Results obtained were compared with commercialized hyaluronic acid fillers. METHODS: Microfat and PRP preparations were performed using standardized techniques. Lipoaspirate residue and blood were obtained from six patients undergoing aesthetic facial microlipofilling. Elastic modulus G' and tan δ (proportion of elasticity versus fluidity) were obtained for the following conditions: microfat alone and microfat mixed with 10, 30 or 50% of PRP. RESULTS: An expected decrease in elastic modulus was observed by adding increase volumes of PRP. Two groups of products with different rheological properties were considered based on statistical differences highlighted regarding the value of G'. Mean tan δ varied from 0.20 ± 0.04 (microfat alone) to 0.28 ± 0.08 (50% microfat/50% PRP). Microfat mixed with 10% of PRP presents consistency comparable to stiffer fillers, whereas microfat mixed with 30 or 50% corresponds to softer fillers. CONCLUSION: Rheological differences were highlighted given the proportion of PRP added to the microfat. Further studies assessing the impact of increased doses of platelets in microfat/PRP mixtures on clinical outcomes should also be investigated. Our findings will help clinicians to choose a mixture that meets their specific needs for a given indication. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

An innovative floating gastro retentive dosage system: formulation and in vitro evaluation.

Over the years, different formulation technologies intended for gastro retentive dosage delivery were investigated and patented. The aim of this study was to develop an innovative floating gastro retentive dosage form (GRDF). The developed technology induces a low-density dosage form containing high active pharmaceutical ingredient (API) concentration by using a hydrophobic dusty powder excipient under specific conditions. The new dosage form was obtained by state of the art wet granulation manufacturing process. An experimental design using a discrete variable and four mixture variables was conducted in order to optimize API concentration and buoyancy of the new dosage form. An apparatus was developed to measure the apparent density of floating tablet. The GRDF was characterized for apparent density, buoyancy, porosity and dissolution using in vitro experimentations.

In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation.

Drug resistance is a major cause of treatment failure in cancer chemotherapy, including that with the extensively prescribed antimetabolite, 5-fluorouracil (5-FU). In this study, we tried to reverse 5-FU resistance by using a double-punch strategy: combining 5-FU with a biochemical modulator to improve its tumoural activation and encapsulating both these agents in one same stealth liposome. Experiments carried out in the highly resistant, canonical SW620 human colorectal model showed a up to 80% sensitisation to 5-FU when these cells were treated with our liposomal formulation. Results with this formulation demonstrated 30% higher tumoural drug uptake, better activation with increased active metabolites including critical-5-fluoro-2-deoxyuridine-5-monophosphate, superior inhibition (98%) of tumour thymidylate synthase, and subsequently, higher induction of both early and late apoptosis. Drug monitoring showed that higher and sustained exposure was achieved in rats treated with liposomal formulation. When examined in a xenograft animal model, our dual-agent liposomal formulation caused a 74% reduction in tumour size with a mean doubling in survival time, whereas standard 5-FU failed to exhibit significant antiproliferative activity as well as to increase the lifespan of tumour-bearing mice. Taken collectively, our data suggest that resistance to 5-FU can be overcome through a better control of its intratumoural activation and the use of an encapsulated formulation.

[Mechanisms and treatment of psoriasis]. / Mécanismes et traitements du psoriasis.

Psoriasis is a common dermatosis that affects 3-5% of the European population. Current treatments offer considerable clinical benefits, but their use is limited due to tolerance problems. Recent years have seen the development of new treatments, used separately or in combination to improve the chronic lesions caused by this disease. T cells play an important role in the pathogenesis of psoriasis. Various techniques target the T cells and the immunological mechanisms involved in their activation. In 2005, treatment of psoriasis is directed essentially towards immunological pathways.

The evaluation of cosmetic and pharmaceutical emulsions aging process using classical techniques and a new method: FTIR.

The purpose of this paper is to show how the utilization of Fourier Transform Infrared (FTIR) spectroscopy can be interesting in stability studying of cosmetic or pharmaceutical "oil in water" (O/W) emulsions. In this study temperature storage tests were performed to accelerate the aging process and evaluate the stability of five emulsions. Emulsions were analyzed by FTIR and classical methods (conductivity, viscosity, pH, texture analysis) in order to determine a method that would enable predicting the emulsion's stability. During the aging process, modifications of chemical functions are measured by FTIR (using spectrometric indices), such modifications included: a decrease of unsaturation index, an increase of carbonyl index and a broadening of the carbonyl band. This band was deconvoluted to evaluate the contribution of different species in the broadening phenomenon, which seems to be caused by the appearance of free fatty acids. Conductimetry seems to be the most sensitive technique to assess physical modifications during emulsion's aging. Concerning the most unstable emulsions, a progressive increasing of conductivity was observed several months before the emulsion destabilizes. Consequently, FTIR and conductimetry are two complementary techniques. Conductimetry is a useful technique to predict emulsion destabilization while FTIR allows the measurement of chemical modifications and helps to understand the chemical mechanisms which occur during the oxidation.

Texture optimization of water-in-oil emulsions.

The aim of this research is to demonstrate the effect of variations in certain parameters of the oily phase (OP) in water-in-oil (W/O) emulsions on rheological and texture properties of finished products. The formulated emulsions were selected according to an optimal experimental procedure. The applied variations were nature of the OP, its volume fraction, the hydrophilic-lipophilic balance (HLB) value, and the surfactant proportion. Results are presented for the followed tests carried out on the emulsions: texture analysis, rheology, and particle size analysis. The oils used in the study were sweet almond oil, liquid paraffin, maize oil, cyclomethicone, dimethicone, and wheat germ oil. The resulting data demonstrate a notable influence of the volume fraction oil on hardness, viscosity, adhesiveness, and cohesiveness of W/O emulsions. Emulsion hardness and viscosity increased as the OP percentage increased; this effect being even more pronounced for the vegetable oils. In contrast, emulsion adhesiveness and cohesiveness decreased as the volume fraction oil increased. The HLB value of the surfactant mixture of the emulsion also influenced hardness, adhesiveness, and elasticity, increasing or decreasing as HLB value did.

EPR study of gamma induced radicals in amino acid powders.

To better understand the composite character of amino acids EPR spectra, the radiolysis and reactions which occurred after irradiation of amino acids, a comparative EPR study of a few simple amino acids has been made in order to identify qualitatively and quantitatively the different radiation-induced radicals in amino acid powders. A spin-trapping methodology has been developed and carried out on irradiated glycine, alanine and valine.

Electron paramagnetic resonance of radicals induced in drugs and excipients by radiation or mechanical treatments.

Radiation as well as mechanical treatments induced in drugs and excipients radicals, which can be studied by electron paramagnetic resonance. A special attention is pointed about the use of electron paramagnetic resonance (EPR) to bring the proof whether or not a drug has been irradiated or not. We also discuss of other methods (thermoluminescence (TL), gas phase chromatography (GPC)) which can be used to bring the same proof in case of irradiated drugs, excipients and cosmetic products.

Stress relaxation studies of granules as a function of different lubricants.

Viscoelastic properties of granules may be studied using stress relaxation. The effect of viscoelastic properties of different lubricants, namely magnesium stearate (Mgst), talc and precirol, on granule compaction properties was examined using texture analyzer TA-XT2i at low pressure. Normalized compact curves of stress relaxation have been discussed in relation to some parameters (flowability, porosity, viscoelasticity as well as particle size). The literature shows that viscoelasticity is always present and it produces an accompanying plastic deformation.This study revealed that bonding in compacted granules lubricated with Mgst was higher than those in compacts lubricated with the other two lubricants being studied. When studying the partial porosity of granule beds, we see that this is the result of stored energy, like the tablet case and the problem of its capping. The small stress relaxation due to talc or precirol suggested that these materials deformed principally by energy storage. However, a qualitative characterization of Mgst as tablet lubricant would be that it avoids the accumulation of stress in the compact that causes the problem of capping due to the entrapped air and therefore facilitates the optimization of pharmaceutical manufacturing. It has been possible to normalize stress relaxation using the Wischert model, represented by the sum of several exponentials, according to the nature of the lubricant. The use of texture analyzer TA-XT2i was considered to be a good technique for the evaluation of the stress relaxation of solid particles in the compression process at low pressure. It permitted the observation that viscoelasticity is influenced by the lubricant used. The brittle fracture index, like Carr's index values, has been correlated with the viscoelastic characteristics of granules.

In-vitro comparative study of buccal mucoadhesive performance of different polymeric films.

A comparison of the buccal mucoadhesive performance of different polymeric films was carried out using texture analyzer TA-XT2i. A large range of putative polymers differing in their chemical nature, molecular structure as well as hydration status was used. The used polymeric films were classified in rank order of buccal mucoadhesive performance, namely carbopol 971P>polycarbophil>Carrrageenan type lambda > Sodium carboxymethylcellulose. Swelling state as well as tensile strength of the used polymeric films was used as measuring parameters of mucoadhesive interaction. These two approaches gave two opposite orders of performance between CMC and Carrrageenan type lambda after a contact time of 15 min. However the measurement of the viscoelastic moduli of the hydrogels gave the same ranking order of mucoadhesive performance after the same contact time. In reference to the previous works, we noted the importance of the molecular weight, the density of charges, the composition of which the chains of molecules are capable to arrange themselves in a network like form, thus those which are characterized by a tan delta<1 (i.e network formation), are those which develop the best synergism with the mucus because of the reinforcement of an established link. The goal of this study is to assess the buccal mucoadhesive performance aiming to optimize the design of drug delivery via buccal mucoadhesive polymeric films

Hot melt coating technology: influence of Compritol 888 Ato and granule size on chloroquine release.

The tangential spray technique was used to coat chloroquine granules with Compritol 888 Ato in a fluidized bed (Glatt GPCG-1,1). After validation of the assay method for chloroquine, dissolution tests were carried out on four size fractions obtained from the same batch of granules. The dissolution profiles obtained showed differences in the rate of release between one fraction and another, despite the fact that each of these fractions had been coated with the same quantity of wax. This suggests that the rate of release of the chloroquine may be adjusted by controlling the size of the granules. Furthermore these dissolution profiles were characterized by a rapid release phase followed by a slow release phase. Examination of the surfaces of the granules from the various size fractions under a scanning electron microscope revealed that Compritol did not form a continuous film but existed rather as a lipid environment around the granule. This lipid environment was made up of solidified droplets of the wax which had become piled up on the surface of the granule. Compression of the granules produced tablets which remained intact until chloroquine dissolution was complete. This undicated that the active substance diffused across the Compritol matrix generated during compression. Determination of the dissolution kinetics using the Higuchi model demonstrated the diffusion release mechanism.

Comparative tablet and rheological properties of new microcrystalline cellulose: direct compression and wet granulation methods.

The overall objective of this study was to compare the rheological properties and tablet characteristics of two new varieties of celluloses (Vivacel 101 and 102), recently produced and commercialized, with the classical varieties of celluloses (Avicel and Elcema). The results showed no significant differences in the rheological properties of Vivacel and Avicel, while significant differences were found between the two celluloses and Elcema. Furthermore, there were no statistically significant differences in the disintegration times and Td values of Vivacel and Avicel. In conclusion, it was found that these new celluloses offer all the known advantages of Avicel.

Controlled-release behavior of diphenhydramine hydrochloride loaded neutral microgranules and coated using ethylcellulose water dispersion.

The development of a loading method of a water-soluble drug using aqueous binding solution to produce microgranules that were then coated with an aqueous ethylcellulose dispersion to sustain drug release is described. The results, in terms of drug used, showed that besides the fluidized bed parameters, the amount of drug dissolved in the binder solution plays an important role in obtaining a satisfying result during the spraying process. Thus, it seems necessary to determine the critical concentration above which the material started to adhere to the interior of the fluidization column, and the possibility of drug layering onto carrier material is aggravated. ANOVA of the time parameter for release of 63.2% of total drug (td) value showed significant influence of ethylcellulose (Aquacoat ECD-30) and dibutyl sebacate concentration on diphenhydramine hydrochloride (DPH) release. The dissolution rate decreased with an increase in polymer concentration. The diffusional exponent n of the Peppas equation indicated that the DPH release kinetic was non-Fickian but approached Fickian diffusion, particularly at higher coating levels.

Evidence for a tissue-specific induction of cutaneous CYP2E1 by dexamethasone.

We studied in mouse the effect of topical application of dexamethasone or salicylic acid, on CYP2E1 and CYP3A expression (proteins and/or mRNA) in liver and skin. Dexamethasone was also administered by intraperitoneal injection. Topical application or intraperitoneal injection of dexamethasone increased cutaneous CYP2E1 (8 and 4-fold respectively) whereas the hepatic level of this isoform showed a slight decrease and hepatic CYP3A expression was increased (3-fold). Cutaneous CYP2E1 was increased (3-fold) after topical treatment by salicylic acid. This compound had no effect on hepatic CYP3A and CYP2E1 expression. Cutaneous CYP3A (protein and mRNA) was not detectable in all groups (control or treated animals). Dexamethasone and salicylic acid increased cutaneous CYP2E1 mRNA level (2.5 and 1.4-fold respectively). In conclusion, dexamethasone and salicylic acid induced cutaneous CYP2E1 protein and mRNA level. Cutaneous CYP2E1 induction by dexamethasone is a tissue-specific process.