Diffusion Cell Experiments Research Articles

Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques

ObjectiveTo analyze the interactions between different structural types of volatile oil components (VOCs) and skin lipid molecules, and investigate the mechanism of volatile oil in Chinese materia medica (VOCMM) as penetration enhancers. MethodsIn this study, 210 different structural types of VOCs were selected from the VOCMM penetration enhancer database, and the molecular docking experiments were conducted with three main lipid molecules of skin: ceramide 2 (CER2), cholesterol (CHL), and free fatty acid (FFA). Each VOC was docked individually with each lipid molecule. Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular structures. Nine specific pathogen-free (SPF) Sprague Dawley (SD) rats were randomly divided into Control, Nootkatone, and 3-Butylidenephthalide groups for in vitro percutaneous experiments, with three rats in each group. The donor pool solutions were 3% gastrodin, 3% gastrodin + 3% nootkatone, and 3% gastrodin + 3% 3-butylidenephthalide, respectively. The penetration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin (Q12, μg/cm2). Results(i) Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA, and hydrogen bonded to the head group of CER2. Among them, sesquiterpene oxides showed the most pronounced binding affinity to CER2. The VOCs with 2 − 4 rings (including carbon rings, benzene rings, and heterocycles) demonstrated stronger binding affinity for three skin lipid molecules compared with the VOCs without intramolecular rings (P < 0.01). (ii) According to the cluster analysis, most of the VOCs that bond well to CER2 had 2 − 3 intramolecular rings. The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner. The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding. (iii) The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60 ± 25.09 μg/cm2, and the transdermal absorption of gastrodin was significantly increased in Nootkatone group (Q12 = <styled-content style-type="number">5503.00</styled-content> ± <styled-content style-type="number">1080.00</styled-content> μg/cm2, P < 0.01). The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group (Q12 = 495.40 ± 56.98 μg/cm2, P > 0.05). (iv) The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. ConclusionThe interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper. This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers, and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.

Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC50) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA). All tested formulations exceeded the IC50 values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05). All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.

Numerical study of doxorubicin transdermal delivery for breast cancer treatment using microneedles.

The lack of in vivo studies on the delivery of doxorubicin within human skin, especially the absence of data on the doxorubicin diffusion coefficient, has made understanding its transdermal delivery kinetics challenging. In this study, as a first step, governing equations and finite element methods were employed to reproduce Franz diffusion cell experiment in human cadaver skin. The application of this experiment representative model with a fitting method resulted in approximate values for the diffusivity of doxorubicin across various skin layers. The estimated values were used later to conduct a comprehensive examination of doxorubicin administration for breast tumor treatments. In a 2D axisymmetric model using Fick's Law and then a microneedles array 3D model, crucial parameters effects on delivery efficiency were examined, such as the microneedle tip diameter, tip-to-tip distance, and tumor depth. As highlighted by the findings of this study, these parameters have an impact on the effectiveness of doxorubicin delivery for treating breast tumors. The focus of this research is on the potential of numerical methods in biomedical engineering, which addresses the urgent need for data on doxorubicin diffusion in human skin and offers valuable insights into optimizing drug delivery strategies for enhanced therapeutic outcomes.

Arc-poration improves transdermal delivery of biomolecules.

To increase skin permeability, various transdermal delivery techniques have been developed. However, due to the stratum corneum as a skin barrier, transdermal delivery remains limited. In this study, we evaluated efficacy and safety of arc-poration as a novel technique disrupting the stratum corneum. Optical images and histological analysis using reconstituted human skin and porcine skin showed that the treatment of arc-poration created micropores with an average diameter of approximately 100 μm only to the depth of the stratum corneum, but not viable epidermis. In addition, the Franz diffusion cell experiment using reconstituted human skin showed a remarkable increase in permeability following pretreatment with arc-poration. Clinical results clearly demonstrated the enhancement of the skin-improving effect of cosmetics by pretreatment of arc-poration in terms of gloss, hydration, flakiness, texture, tone, tone evenness, and pigmentation of skin, without causing abnormal skin responses. The concentration of ozone and nitrogen oxides generated by arc-poration was below the permissible value for the human body. Arc-poration can increase skin permeability by creating stratum corneum-specific micropores, which can enhance the skin-improving effect of cosmetics without adverse responses.

Essential Oils Distilled from Colombian Aromatic Plants and Their Constituents as Penetration Enhancers for Transdermal Drug Delivery.

The study aimed to determine the enhanced effects of essential oils (EOs) and plant-derived molecules (PDMs) as penetration enhancers (PEs) for transdermal drug delivery (TDD) of caffeine. A 1% w/w solution of eight EOs and seven PDMs was included in the 1% caffeine carbopol hydrogel. Franz diffusion cell experiments were performed using mice with full-thickness skin. At various times over 24 h, 300 μL of the receptor were withdrawn and replaced with fresh medium. Caffeine was analyzed spectrophotometrically at 272 nm. The skin irritation effects of the hydrogels applied once a day for 21 days were investigated in mice. The steady-state flux (JSS) of the caffeine hydrogel was 30 ± 19.6 µg cm-2 h-1. An increase in caffeine JSS was induced by Lippia origanoides > Turnera diffusa > eugenol > carvacrol > limonene, with values of 150 ± 14.1, 130 ± 47.6, 101 ± 21.7, 90 ± 18.4, and 86 ± 21.0 µg cm-2 h-1, respectively. The Kp of caffeine was 2.8 ± 0.26 cm h-1, almost 2-4 times lower than that induced by Lippia origanoides > Turnera diffusa > limonene > eugenol > carvacrol, with Kp values of 11 ± 1.7, 8.8 ± 4.2, 6.8 ± 1.7, 6.3 ± 1.2, and 5.15 ± 1.0 cm h-1, respectively. No irritating effects were observed. Lippia origanoides, Turnera diffusa, eugenol, carvacrol, and limonene improved caffeine's skin permeation. These compounds may be as effective as the PE in TDD systems.

Salt Transport in Crosslinked Hydrogel Membranes Containing Zwitterionic Sulfobetaine Methacrylate and Hydrophobic Phenyl Acrylate.

Produced water is a by-product of industrial operations, such as hydraulic fracturing for increased oil recovery, that causes environmental issues since it includes different metal ions (e.g., Li+, K+, Ni2+, Mg2+, etc.) that need to be extracted or collected before disposal. To remove these substances using either selective transport behavior or absorption-swing processes employing membrane-bound ligands, membrane separation procedures are promising unit operations. This study investigates the transport of a series of salts in crosslinked polymer membranes synthesized using a hydrophobic monomer (phenyl acrylate, PA), a zwitterionic hydrophilic monomer (sulfobetaine methacrylate, SBMA), and a crosslinker (methylenebisacrylamide, MBAA). Membranes are characterized according to their thermomechanical properties, where an increased SBMA content leads to decreased water uptake due to structural differences within the films and to more ionic interactions between the ammonium and sulfonate moieties, resulting in a decreased water volume fraction, and Young's modulus increases with increasing MBAA or PA content. Permeabilities, solubilities, and diffusivities of membranes to LiCl, NaCl, KCl, CaCl2, MgCl2, and NiCl2 are determined by diffusion cell experiments, sorption-desorption experiments, and the solution-diffusion relationship, respectively. Permeability to these metal ions generally decreases with an increasing SBMA content or MBAA content due to the corresponding decreasing water volume fraction, and the permeabilities are in the order of K+ > Na+ > Li+ > Ni2+ > Ca2+ > Mg2+ presumably due to the differences in the hydration diameter.

Combined Dopamine and Grape Seed Extract-Loaded Solid Lipid Nanoparticles: Nasal Mucosa Permeation, and Uptake by Olfactory Ensheathing Cells and Neuronal SH-SY5Y Cells

We have already formulated solid lipid nanoparticles (SLNs) in which the combination of the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) was supposed to be favorable for Parkinson's disease (PD) treatment. In fact, GSE supply would reduce the PD-related oxidative stress in a synergic effect with DA. Herein, two different methods of DA/GSE loading were studied, namely, coadministration in the aqueous phase of DA and GSE, and the other approach consisting of a physical adsorption of GSE onto preformed DA containing SLNs. Mean diameter of DA coencapsulating GSE SLNs was 187 ± 4 nm vs. 287 ± 15 nm of GSE adsorbing DA-SLNs. TEM microphotographs evidenced low-contrast spheroidal particles, irrespective of the SLN type. Moreover, Franz diffusion cell experiments confirmed the permeation of DA from both SLNs through the porcine nasal mucosa. Furthermore, fluorescent SLNs also underwent cell-uptake studies by using flow cytometry in olfactory ensheathing cells and neuronal SH-SY5Y cells, evidencing higher uptake when GSE was coencapsulated rather than adsorbed onto the particles.

Novel episcleral implants of sunitinib can depress ocular neovascularization under ex‐vivo conditions

AbstractBackground: Current management of posterior segment disease such as Age‐related Macular degeneration (AMD) and Diabetic Macular Edema (DME) is by monthly Intravitreal injections of Anti‐VEGF agents (IVT). IVT therapy suffers from various serious drawbacks such as highly invasive procedure and risk of ocular tissue damage. Moreover, Lower response rate of Anti‐VEGF agents in patients also demands development of novel alternative therapies. One of the major challenge of posterior segment drug delivery is selection of suitable in‐vivo models for pharmacokinetic and therapeutic screening due to highly localized nature of eye leading limited choices animals that resemble human ocular anatomy. Hence we aim to novel episcleral implant platform for posterior segment drug delivery along with using suitable ex‐vivo assays for therapeutic estimation of developed drug delivery systems.Methods: The Implants loaded with sunitinib malate were fabricated using a polymeric blend of gelatin and polyglycerol sebacate (PGS) by electrospinning technique. The effect of polymer blending and drug loading on morphology and in‐vitro drug release profile by scanning electron microscopy and shaking incubator drug release method. Further, the effect of electrospinning and polymer blending on mucoadhesion was studied by mucin agar plate method. Transscleral drug permeation and the secondary depot formation of sunitinib following episcleral application were studies Franz diffusion cell experiment. The biocompatibility of implant was tested on ARPE‐19 cells and the effect of treatment on cell morphology was studied by crystal violet staining. The therapeutic efficacy of episcleral implants was tested by ex‐vivo choroidal angiogenesis assay.Results: The electrospinning process lead to development of highly porous and flexible implants. It was found that polymer blending has profound effect on the morphology as well as in vitro drug release of implants. The addition of PGS lead to thinner fibres within implant and it also lead to sustained release of sunitinib over the period of one week. The drug loading did not has proficient effect on the morphology of implants; however, higher loading lead to sustained release of sunitinib over the release period. The electrospinning process lead to enhanced mucoadhesion that could possibly due to increased surface area and improved contact angle. The implants were found to be biocompatible and did not alter the morphology of ARPE‐19 cells upon treatment as observed by crystal violet staining. The drug release samples of implants in cell culture media were tested upon ex‐vivo rat choroidal angiogenesis assay where it was observed that the release samples were able to suppress the ocular neovascularization significantly when compared with untreated samples.Conclusions: We can conclude that sunitinib loaded episcleral implants could be a promising alternative for management of disease with posterior segment neovascularization such as AMD and DME. The polymer blending of different polymers along with electrospinning technique could aid in development of novel episcleral implants with sustained release of medicinal agents. The electrospun implant platform could also be used for anterior segment drug delivery as well. Finally ex‐vivo rat choroidal angiogenesis assay could be a great tool for therapeutic screening of ocular drug delivery systems.

Collaborative permeation of drug and excipients in transdermal formulations. In vitro scrutiny for ethanol:limonene combinations

Enhancement of skin permeation of drugs is affected by the simultaneous co-permeation of excipients that hinder the predictivity of in vitro tests. The collaborative effects of two permeation enhancers (ethanol and d-limonene) of a lipophilic drug (alprazolam) have been simultaneously assessed in human skin under different in vitro conditions: integrated setups of diffusion cell experiments with selective concentration gradients of permeants (asymmetric) or without (symmetric) have been combined with coadministration dosages (all-in-one) at different concentrations or short-time skin pretreatment to scrutiny this mutual performance.Findings: Drug permeation is increased under moderated supersaturation but reaches a stationary level above 33 % of its solubility. Ethanol in absence of a concentration gradient increases ca.5 times basal drug permeation. Limonene until 20 % permeates human skin proportionally to its donor concentration but its effect does not depend on ethanol in symmetric conditions and is based on skin imbibition rather than on a carry-on effect. Simultaneous permeation of ethanol and limonene reaches a stationary state after 1.5 h, enough time to achieve maximal enhancement of alprazolam permeation. Additive enhancement is based on ethanol solubilisation maximized by skin saturation of terpene. Complementary analyses of skin disruption published in the literature are in line with these assessments and consolidate them.

Design and development of an automated experimental setup for ion transport measurements.

The ion transport measurements using various ion-exchange membranes (IEMs) face several challenges, including controllability, reproducibility, reliability, and accuracy. This is due to the manual filling of the solutions in two different reservoirs in a typical diffusion cell experiment with a random flow rate, which results in the diffusion through the IEM even before turning on the data acquisition system as reported so far. Here, we report the design and development of an automated experimental setup for ion transport measurements using IEMs. The experimental setup has been calibrated and validated by performing ion transport measurements using a standard nanoporous polycarbonate membrane. We hope that the present work will provide a standard tool for realizing reliable ion transport measurements using ion-exchange membranes and can be extended to study other membranes of various pore densities, shapes, and sizes.

Hydroxyl Group-Targeted Conjugate and Its Self-Assembled Nanoparticle of Peptide Drug: Effect of Degree of Saturation of Fatty Acids and Modification of Physicochemical Properties.

PurposeTo conjugate different degree of saturation of C18 fatty acids (stearic acid, oleic acid, and linoleic acid) with the hydroxyl groups of leuprolide acetate (LEU acetate) and to investigate the controlled release and enhanced permeability through self-assembled nanoparticles (L18FNs).MethodsYamaguchi esterification with benzoyl chloride and DMAP (4-Dimethylaminopyridine) allowed the conjugation of the fatty acid to the hydroxyl group of LEU. The three conjugates were then designated as stearic acid-conjugated LEU, LSC, oleic acid-conjugated LEU, LOC, and linoleic acid-conjugated LEU, LLC, respectively. The conjugates (L18FCs) were purified using preparative HPLC (Prep-HPLC) and identified through various instrumental analyses.ResultsThe zeta potential, particle size, and morphology of each L18FNs were evaluated. In the case of LSNs, the zeta potential value was relatively low and the particle size was larger than LONs and LLNs owing to the higher hydrophobicity of saturated fatty chain, while the LLNs showed a higher zeta potential and smaller particle size. In human plasma, LLC showed the fastest degradation rate with the highest accumulative drug release. The permeability of L18FNs was analyzed through the Franz diffusion cell experiment, confirming that the degree of saturation of fatty acids affects the permeability of LFNs. While the permeability of LSNs was not significantly enhanced due to higher particle size after nanonization, LONs and LLNs increased 1.56 and 1.85 times in permeation, respectively, compared to LEU.ConclusionUtilization of different degree of saturation of fatty acids to conjugate a peptide drug could provide pharmaceutical versatility via self-assembly and modification of physicochemical properties.

Bletilla striata polysaccharide microneedle for effective transdermal administration of model protein antigen.

Traditional vaccination relies on subcutaneous injection or intramuscular injection, which requires professional medical personnel and is accompanied by the risk of needle-related diseases and injuries. Therefore, to promote immunization coverage and reduce costs, it is necessary to provide a new method of vaccine administration. Dissolving microneedle (DMN) has been proposed as an alternative to hypodermic needles, providing prospects for self-inoculation and increasing immunogenicity by directly targeting skin dendritic cells. This study reported the successful preparation and characterization of Bletilla striata polysaccharide microneedles (BMNs) and investigated the potential of this natural material-based DMN as a vaccine carrier. The prepared BMNs exhibited more excellent mechanical properties and stability compared with microneedles made of hyaluronic acid and polyvinyl alcohol. BMNs had good cell compatibility, low bacterial skin permeability, slight irritation to the skin, and no infection or inflammation in the body. In addition, as shown by circular dichroism, the molecular structure of the antigen ovalbumin (OVA) loaded in BMN did not change during storage for 21days. The Franz diffusion cell experiment showed 76.74% of OVA was released to the skin within 3h. These encouraging findings indicate that the BMNs can be a promising tool for effective vaccine delivery.

Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection.

Ungual formulations are regularly tested using human nails or animal surrogates in Franz diffusion cell experiments. Membranes sometimes less than 100 µm thick are used, disregarding the higher physiological thickness of human nails and possible fungal infection. In this study, bovine hoof membranes, healthy or infected with Trichophyton rubrum, underwent different imaging techniques highlighting that continuous pores traversed the entire membrane and infection resulted in fungal growth, both superficial, as well as in the membrane’s matrix. These membrane characteristics resulted in substantial differences in the permeation of the antifungal model substance bifonazole, depending on the dosage forms. Increasing the thickness of healthy membranes from 100 µm to 400 µm disproportionally reduced the permeated amount of bifonazole from the liquid and semisolid forms and allowed for a more pronounced assessment of the effects by excipients, such as urea as the permeation enhancer. Similarly, an infection of 400-µm membranes drastically increased the permeated amount. Therefore, the thickness and infection statuses of the membranes in the permeation experiments were essential for a differential readout, and standardized formulation-dependent experimental setups would be highly beneficial.

Modelling of solute transport and microbial activity in diffusion cells simulating a bentonite barrier of a spent nuclear fuel repository

Microbial sulfate reduction possesses a potential risk for the long-term safety of spent nuclear fuel repositories because under expected repository conditions sulfide is the main corroding agent for copper and copper-coated steel canisters foreseen in the Scandinavian disposal concepts. It is thus essential to understand and quantify the processes and factors impacting microbial sulfide production within and around compacted bentonite, which is planned to be used as a buffer material in many repository concepts. In the present study reactive transport modelling was applied to increase the understanding of diffusion cell experiments, which brought sand layers with or without inoculated microorganisms in contact with compacted and saturated bentonites of different mineralogy. Model results obtained for a sodium bentonite from Wyoming and a calcium bentonite from Bulgaria gave strong evidence for the activation of bentonite indigenous microorganisms, at least in zones of a reduced density close to the bentonite/sand interface. For all experiments, the calculations indicated that after an initial phase of favourable conditions, microbial activity was limited by the (bio-)availability of organic carbon. In the Bulgarian bentonite, characterized by a very low gypsum content, the model furthermore suggested some intermediate control of microbial sulfate reduction by sulfate availability. The present study thus demonstrated the rapid evolution of a transport limited system in settings where zones of microbial activity are in contact with highly compacted microbially-inactive bentonite. Gypsum dissolution calculated and determined experimentally for the Wyoming bentonite indicated significant gypsum dissolution in the first 2 cm from the interface during 450 days. The reactive transport model applied successfully in this study for the description of an experimental system followed the conceptual models for microbial sulfate reduction in repository settings. The results obtained offer insights regarding the mechanism and magnitude of biogeochemical reactions that might occur in the vicinity of the bentonite buffer surrounding the waste canister and in so doing, may be relevant for the near field of HLW repositories.

Higher-voltage asymmetric-electrolyte metal-air batteries

Higher-voltage asymmetric-electrolyte metal-air batteries

Permeability coefficients and vapour pressure determination for fragrance materials.

This study aims to correlate new experimental data relevant to the description of the combined evaporation/permeation process of a perfume applied onto the skin. The vapour pressure data were measured by thermogravimetric analysis (TG-DTA). The Antoine constants and the Clarke and Glew parameters were determined for the same set of fragrance molecules to describe its low vapour pressures at new temperature ranges. The permeability coefficient of a set of 14 fragrance molecules in ethanolic solution was determined by Franz diffusion cell experiments, using porcine skin. The samples were analysed by gas chromatography with a flame ionization detector (GC/FID) and high-performance liquid chromatography with UV visible detector (HPLC/UV). A QSAR model was proposed to correlate the experimental data. The Antoine constants were determined and presented low standard deviations. The Clarke and Glew physically significant parameters were obtained along with its statistical analysis. The fitting is good since the magnitude order is in accordance with the literature, associated with the low correlation between the estimated parameters and low standard deviations. The presented correlation, based on a mixture using only ethanol as solvent, showed better results than previous QSAR models with a standard relative deviation ( of 0.190, a standard error (SE) of 0.397 and a determination coefficient (R2 ) of 0.7786. The dataset is still small compared to larger and more general QSAR models; however, it is much more specific as to the type of solvent and class of materials studied. This work represents an advance for the modelling of the perfume diffusion process since it specifies important properties that until then had been treated in a more general way.

Impact of low ionic strength on DGT sampling with standard APA gels: Effect of pH and analyte

Only a limited and scattered knowledge is currently available on the conditions leading to the occurrence of sampling alteration at low ionic strength (<10−3 mol L−1) with DGT (diffusive gradients in thin films technique). In this study, the role of the pH and the charge of the analyte were comprehensively evaluated with DGT equipped with APA (polyacrylamide with agarose-derivative crosslinker) diffusive gels and ZrO or Chelex binding phases. The sampling of four cations (CdII, CuII, NiII and PbII) and two anions (AsV and CrVI) was compared for pH 4, 6 and 8 at common (10−2 mol L−1) and low (10−4 mol L−1) ionic strengths. Results showed that the sampling was modified at low ionic strength only in the most acidic condition (pH 4) for both anions and cations with an opposite incidence: cations' sampling was halved whereas anions’ sampling was increased. Furthermore, cations sampling alteration was similarly reproduced using diffusion cell experiments, which requires only the APA gel, indicating that the binding layer does not participate in the low ionic strength effect. The intensity of DGT sampling modification was consistent with a prediction based on Donnan partitioning of analytes at gel/solution interface for several valences (from -I to + III). All these results strongly suggest that the APA diffusive gels carry positive charges that create a Donnan effect at low ionic strength. Since no ionic strength effect could be evidenced at pH 6 and 8, it can be reasonably assumed that this effect occurs only marginally for DGT deployments in most natural waters.

FORMULATION AND EVALUATION OF METFORMIN HCL RELEASE FROM TOPICAL PREPARATION USING TWO DIFFERENT TYPES OF MEMBRANE

Objective: Present study was carried to formulate and evaluate the transdermal ointment containing the metformin HCl active ingredient and to assess their Physicochemical studies.&#x0D; Methods: Metformin HCl ointment was prepared with various thymol oil concentrations. Ointments were assessed with different characterizations; Physical appearance, viscosity, pH, drug content, Consistency, homogeneity, consistency. Differential scanning calorimetry analysis, XRD studies. It was used in vitro via using Franz cells along with the use of two membranes i.e. Nylon and cellulose membrane.&#x0D; Results: SEM and XRD studies showed that there were no physical and chemical interactions between excipients and drug. All the formulations showed good physicochemical characteristics. The formulation showed different releases. It was observed that nylon had better release properties as compared to cellulose.&#x0D; Conclusion: In the study conducted here, it was observed that Nylon membrane showed better discriminating power to compare among the formulation. This indicates that it has gotten prime importance to watch the effect of the membrane upon the release pattern of the various formulations. In order to improve the formulation, we can use in vitro diffusion cell experiments of transdermal drug delivery.

A novel composite of micelles and hydrogel for improving skin delivery of hydrocortisone and application in atopic dermatitis therapy

Transdermal drug delivery is an attractive and potentially more effective method of localized and systemic treatment with minimal side effects and greater safety than current techniques. However, a limitation of drug delivery through the skin is the presence of the stratum corneum, which inhibits the development of clinical applications. Furthermore, in order to achieve better therapeutic outcomes, a number of traditional topically-applied preparations have high drug concentrations which can lead to skin irritation and formation of lesions. The use of safer and milder hydrocortisone (HC) cream for the treatment of moderate to severe atopic dermatitis (AD) is not considered due to its low potency and poor absorption through the skin, even at a dose of 1%. Therefore, in the present study, a composite of HC-loaded micelles and carbomer hydrogel was designed to enhance transdermal HC transport to improve topical therapy of AD. Franz diffusion cell experiments indicated that this composite significantly increased the skin permeation rate and cumulative quantity of HC transferred, which were greater than a 9-fold and 50-fold increase relative to HC cream, respectively. In addition, the composite system was demonstrated to rapidly and effectively ameliorate inflammatory symptoms on an AD-like mouse model and greatly reduce skin irritation and adverse systemic effects compared to HC cream. As described above, the novel HC formulation was a feasible strategy to provide safe and effective treatment in AD therapy.

Controlled grafting of polymer brush layers from porous cellulosic membranes

Dense polymer brushes on porous supports present powerful routes toward fouling-resistant coatings and ultra-thin, mechanically-stable selective layers. However, characterization of polymer chains grafted from nonideal, planar substrates often relies on indirect methods to determine the length, density, and location of polymeric brushes. In this study, we explore new methods to control and characterize the properties of polymer brush layers. Starting from hand-cast cellulose films and commercial cellulose membranes, we use surface-initiated atom transfer radical polymerization to graft polymeric chains. We tailor brush density and simultaneously stabilize the support by varying the proportions of initiator and crosslinker esterified to the cellulose substrate. On films with grafted polyacrylic acid (PAA) chains, we use the silver-binding method to determine brush density. We analyze brush growth behavior by directly cleaving chains from the surface of films for analysis by size exclusion chromatography, uniquely observing the divergence of two distinct populations of differing length beyond a certain molecular weight. Such behavior would be important to consider if the alignment of block copolymer layers is absolutely necessary in an application. By controlled contact of polymerization solution with the top surface, we show that brush growth can be partially directed to the top surface for asymmetric cellulose membranes with relatively low molecular weight cutoffs. In a semi-quantitative method to locate brush growth, depleted uranium was bonded to grafted PAA chains, and targeted emission x-ray spectroscopy was conducted for comparison of uranium content in various regions. Finally, we used our developed methods and findings to inform the synthesis of homopolymer and diblock copolymer brush layers, which we then used as selective layers in pressure-driven filtration and diffusion cell experiments.