EFECTO DE UN SURFACTANTE NO IONICO EN LA PERMEABILIDAD DE BUTORFANOL A TRAVES DE MUCOSA NASAL EQUINA

Implementation of intranasal administration for the delivery of drugs with site of action into the central nervous system, such as butorphanol, became a potential choice in equine medicine. In this study, using Franz-diffusion cells the in vitro permeation rate through respiratory and olfactory equine nasal mucosa of two butorphanol formulations was estimated and compared. Both formulations had the same composition, was the exception for formulation 2, that contained 2, 5 x 10 -4 M of a non-ionic surfactant (tween 80). Butorphanol administered dose was 24, 4 mg/cm2. Plots of the cumulative amounts of butorphanol against time were constructed, where maximum flux values at the steady state (Jss), apparent permeability coefficients (Kp) and lag-time (tlag) were estimated. The Jss and Kp show that permeation of butorphanol through olfactory mucosa is different than respiratory mucosa. Moreover, Jss for formulation 2 was higher than formulation 1 in both anatomical areas, probably for the effect of the surfactant. The present results are promising to carry on with the development of formulation of butorphanol for intranasal administration.

Topical Delivery of Niacinamide to Skin Using Hybrid Nanogels Enhances Photoprotection Effect

Niacinamide (NIA) has been widely used in halting the features of ageing by acting as an antioxidant and preventing dehydration. NIA’s physicochemical properties suggest difficulties in surpassing the barrier imposed by the stratum corneum layer to reach the target in the skin. To improve cutaneous delivery of NIA, a hybrid nanogel was designed using carrageenan and polyvinylpyrrolidone polymers combined with jojoba oil as a permeation enhancer. Three different types of transethosomes were prepared by the thin-film hydration method, made distinct by the presence of either an edge activator or a permeation enhancer, to allow for a controlled delivery of NIA. Formulations were characterized by measurements of size, polydispersity index, zeta potential, encapsulation efficiency, and loading capacity, and by evaluating their chemical interactions and morphology. Skin permeation assays were performed using Franz diffusion cells. The hybrid hydrogels exhibited robust, porous, and highly aligned macrostructures, and when present, jojoba oil changed their morphology. Skin permeation studies with transethosomes-loaded hydrogels showed that nanogels per se exhibit a more controlled and enhanced permeation, in particular when jojoba oil was present in the transethosomes. These promising nanogels protected the human keratinocytes from UV radiation, and thus can be added to sunscreens or after-sun lotions to improve skin protection.

Assessment of the Effect of Structural Modification of Ibuprofen on the Penetration of Ibuprofen from Pentravan® (Semisolid) Formulation Using Human Skin and a Transdermal Diffusion Test Model

The effect of transdermal vehicle (Pentravan®) on skin permeability was examined for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with new L-valine alkyl esters [ValOR][IBU]. The percutaneous permeation across the human skin and transdermal diffusion test model (Strat-M® membranes) of ibuprofen and its structural modification were measured and compared using Franz diffusion cells. For comparison, the penetration of ibuprofen from a commercial product was also investigated. The cumulative amount of drug permeated through human skin at the end of the 24 h study was highest for ibuprofen derivatives containing propyl (C3), isopropyl (C3), ethyl (C2), and butyl (C4) esters. For Strat-M®, the best results were obtained with the alkyl chain length of the ester from C2 to C5. The permeation profiles and parameters were appointed, such as steady-state flux, lag time, and permeability coefficient. It has been shown that L-valine alkyl ester ibuprofenates, with the propyl, butyl, and amyl chain, exhibit a higher permeation rate than ibuprofen. The diffusion parameters of analyzed drugs through human skin and Strat-M® were similar and with good correlation. The resulting Pentravan-based creams with ibuprofen in the form of an ionic pair represent a potential alternative to other forms of the drug-containing analgesics administered transdermally. Furthermore, the Strat-M® membranes can be used to assess the permeation of transdermal preparations containing anti-inflammatory drugs.

Electrospun Nanofiber and Cryogel of Polyvinyl Alcohol Transdermal Patch Containing Diclofenac Sodium: Preparation, Characterization and In Vitro Release Studies

Transdermal drug delivery systems (TDDS) have drawn more interest from pharmaceutical scientists because they could provide steady blood levels and prevent the first-pass metabolism over a longer period. Polyvinyl alcohol (PVA) has been widely used in this application due to its biocompatibility, non-toxicity, nanofiber and hydrogel-forming ability. Despite those benefits, their morphology would easily be destroyed by continuous water absorption and contribute to burst drug release due to its hydrophilicity. The aim of this study was to prepare the diclofenac sodium (DS)-medicated dual layer PVA patch using a combination of electrospinning and cryogelation (freeze–thaw) methods to improve the physicochemical properties and drug compatibility and investigate the release of the DS-medicated dual layer PVA patch. Morphological observations using scanning electron microscopy (SEM) verified the polymer−polymer interaction between both layers, whereas Fourier transform infrared (FTIR) spectroscopy has demonstrated the compatibility of DS in PVA matrix up to 2% w/v of PVA volume. The DS loads were found amorphously distributed efficaciously in PVA matrix as no visible spectra of DS–PVA interaction were detected. The DS-medicated dual layer PVA patch with a thicker nanofiber layer (3-milliliter running volume), three freeze–thaw cycles and 2% DS loading labeled as 2%DLB3C show the lowest swelling capacity (18.47%). The in vitro assessment using Franz diffusion cells showed that the 2%DLB3C indicates a better sustained release of DS, with 53.26% of the DS being released after 12 h. The 2%DLB3C owned a flux (Jss) of 0.256 mg/cm2/h and a permeability coefficient (Kp) value of 0.020 cm/h. Thus, the results demonstrate that DS-medicated dual layer PVA patches prepared via a combination of electrospinning and cryogelation are capable of releasing drugs for up to 24 h and can serve as a drug reservoir in the skin, thereby extending the pharmacologic effects of DS.

Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery—Starting Points and Recent Developments

During the last decades, several technologies were developed for testing drug delivery through the dermal barrier. Investigation of drug penetration across the skin can be important in topical pharmaceutical formulations and also in cosmeto-science. The state-of- the-art in the field of skin diffusion measurements, different devices, and diffusion platforms used, are summarized in the introductory part of this review. Then the methodologies applied at Pázmány Péter Catholic University are shown in detail. The main testing platforms (Franz diffusion cells, skin-on-a-chip devices) and the major scientific projects (P-glycoprotein interaction in the skin; new skin equivalents for diffusion purposes) are also presented in one section. The main achievements of our research are briefly summarized: (1) new skin-on-a-chip microfluidic devices were validated as tools for drug penetration studies for the skin; (2) P-glycoprotein transport has an absorptive orientation in the skin; (3) skin samples cannot be used for transporter interaction studies after freezing and thawing; (4) penetration of hydrophilic model drugs is lower in aged than in young skin; (5) mechanical sensitization is needed for excised rodent and pig skins for drug absorption measurements. Our validated skin-on-a-chip platform is available for other research groups to use for testing and for utilizing it for different purposes.

Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes

The steady improvement and optimization of transdermal permeation is a constant and challenging pharmaceutical task. In this study the influence of poly(lactide-co-glycolide) (PLGA) nanoparticles on the dermal permeation of the anti-inflammatory drug flufenamic acid (FFA) was investigated. For this aim, different vehicles under non-buffered and buffered conditions and different skin models (human heat separated epidermis and reconstructed human epidermis equivalents) were tested. Permeation experiments were performed using static Franz diffusion cells under infinite dosing conditions. Already the presence of drug-free nanoparticles increased drug permeation across the skin. Drug permeation was even enhanced when applying drug-loaded nanoparticles. In contrast, buffered vehicles with different pH values (pH 5.4–7.4) revealed the influence of the pH on the permeation of FFA. The change of the surrounding pH of the biodegradable nanoparticulate system was demonstrated and visualized using pH-sensitive fluorescent probes. While a potential contribution of hair follicles could be ruled out, our data suggest that the enhanced permeation of FFA through human skin in the presence of PLGA nanoparticles is mediated by a locally decreased pH during hydrolytic degradation of this polymer. This hypothesis is supported by the observation that skin permeation of the weak base caffeine was not affected.

Nanemulsions of foodstuffs and their nutritiological and valleological characteristics

Annotation. The use of nanotechnology in the medical, food, pharmaceutical, biotechnology industries today is an important scientific progress and valuable human heritage. Nanoemulsion technology is an ideal method for the manufacture of encapsulating systems for functional compounds, as it prevents their biotechnological biodegradation and improves their functional availability in the cells of the body. The aim of the article is a scientific-theoretical and practical review of the nutritional and valeological properties of nanoemulsions, their use for encapsulation of various nutraceuticals, namely fat-soluble vitamin D. The in vitro experiment was performed using Franz diffusion cells to study the release of bioactive compounds from nanocarriers. The cytotoxicity of nanoemulsions was investigated by analyzing the proliferation of thiazolyl blue tetrazolium bromide (TTB) cells and nasal epithelial cells as an “in vitro” model. The article provides to characterize the nutritional and valeological properties of nanoemulsions and to experimentally investigate hydrogels based on nanoemulsions as biocarriers of vitaminized compounds. During the study, low- and high-energy nanoemulsions were created, which were used for encapsulation of vitamin D3 and biologically active supplement - curcumin. Loaded nanoemulsions are added to homopolymer and copolymer hydrogels based on polysaccharides and their combinations. Both nanoemulsions and hydrogels are structurally characterized to evaluate the effect of the composition on the emulsification process by their properties. The cytotoxic effect of nanoemulsions "in vitro" on the epithelium of nasal cells, which had a positive therapeutic effect, was studied. In the future, further exploration and research will investigate the use of nanoemulsions as biocarriers for other vitamins and bioactive substances.

Pengaruh Kombinasi Polimer Polivinil Pirolidon dan Etil Selulosa terhadap Karakteristik dan Uji Penetrasi Formulasi Transdermal Patch Ekstrak Bawang Dayak (Eleutherine palmifolia (L)

The transdermal patch can deliver the active substance with good bioavailability, then made formulations of such preparations from dayak onion extract, which has a compound content of flavonoids, with a combination of polymer PVP K30 and ethyl cellulose to produce transdermal patches with good physical evaluation and penetration. The research aims to carry out the effect and ideal formulation of transdermal patches of dayak onion extract with a combination of polymers PVP K30 and ethyl cellulose based on physical evaluation and penetration—manufacture of transdermal patches using the solvent evaporation method. Physical evaluation includes organoleptic testing, weight uniformity, thickness, folding resistance, and moisture testing. Then evaluate the penetration of the active substance using Franz diffusion cells. Analyze data with One Way ANOVA. The physical evaluation results of weight uniformity, patch thickness, folding resistance, and moisture test of transdermal patches on F1, F2, F3, and F4 meet the requirements. As for the results of penetration tests, F1, F2, F3, and F4 can be penetrated from 120 minutes to 180 minutes with the concentration of active substances that are linearly penetrated. The combination of polymers PVP K30 and ethylcellulose has affected the physical evaluation of transdermal patches of dayak onion extract. Based on the physical evaluation and penetration test in vitro obtained, the most optimal formula results are F3 with comparison PVP K30 and ethyl cellulose (100:300).

Effect of two surfactants on in vitro permeation of butorphanol through horse nasal mucosa

The aim of the present study was to evaluate the effect of two surfactants on in vitro permeation of butorphanol through equine nasal mucosa. Franz diffusion cells and equine nasal mucosa were used. Three formulations were developed based on citric acid, sodium citrate, sodium chloride, and butorphanol tartrate and administered at a 24.4 g cm-3 dose. Control formulation lacked any penetration enhancer. Formulation 1 (F1) had a cationic surfactant (cetrimonium bromide) and formulation 2 (F2) had a non-ionic surfactant (Tween 80). Statistically comparing flux values at the steady state (Jss), apparent permeability coefficient (Kp), and lag-time from control, F1 and F2 for the respiratory region does not show statistically significant differences (α= 0.05). However, statistically significant differences were found on the Jss and Kp, values from control, F1, and F2 in olfactory mucosa. A statistical analysis on the latter showed significant differences between the Jss values of F1 and F2 and between control and F2. Based on this, Tween 80 proved to be a promising excipient in developing intranasal butorphanol formulations in equines since it increases its passage through the nasal mucosa. These results are very promising to continue with the development of intranasal butorphanol formulation in equines.

Development of a novel nanoemulgel formulation containing cumin essential oil as skin permeation enhancer

Essential oils have been proposed as promising non-toxic transdermal permeation enhancers. Their use is limited because of their low water solubility. The use of nanotechnology-based strategies is one of the ways to overcome this limitation. This study aimed to explore the transdermal permeation enhancing capability of cumin essential oil in nanoemulgel systems containing diclofenac sodium. Cumin essential oil nanoemulsion was produced by high-pressure homogenization technique. The formulation was optimized by changing HLB values in a range of 9.65–16.7 using different surfactant mixtures, namely, Tween 20, Tween 80, and Span 80. Preparations were characterized by polydispersity index, droplet size, and zeta potential. Nanoemulsion with concentrations of 2 and 4% essential oil was incorporated into 0.75% Carbopol gel matrix to make nanoemulgel formulation, and its permeation enhancing effect was performed through Franz diffusion cells. Antinociceptive activities of the formulations were measured in thermal (tail-flick) and chemical (formalin) models of nociception in mice. Characterization exhibited that at HLB value of 9.65, the smallest particle size (82.20 ± 5.82 nm) was formed. By increasing the essential oil percentage in the nanoemulgel from 1 to 2%, the permeation of diclofenac increased from 28.39 ± 1.23 to 34.75 ± 1.07 µg/cm2 at 24 h. The value of permeation from the simple gel (21.18 ± 2.51 µg/cm2) and the marketed product (22.97 ± 1.92 µg/cm2) was lower than the formulations containing essential oil. Nanoemulgel of diclofenac containing essential oil showed stronger antinociceptive effects in formalin and tail-flick tests than simple diclofenac gel and marketed formulation. In conclusion, the study proved that nanoemulgel formulation containing cumin essential oil could be considered as a promising skin enhancer to enhance the therapeutic effect of drugs. Graphical abstract