Franz Diffusion Cells Research Articles

Transdermal delivery of captopril using poly(vinyl pyrrolidone)/poly(vinyl alcohol)-based dissolving and hydrogel-forming microneedles: A proof of concept

Captopril (CAP) is an angiotensin-converting enzyme (ACE) inhibitor that has been widely used to treat hypertension. Oral administration of CAP has been associated with bioavailability and frequency issues, affecting patient compliance. Thus, it is essential to investigate an alternative route for overcoming those problems, namely transdermal. Microneedles is a promising strategy to enhance skin permeation of hydrophilic drugs, such as CAP. This research aimed to develop poly(vinyl pyrrolidone)/poly(vinyl alcohol)-based dissolving microneedles (DMN) and hydrogel-forming microneedles (HFMN) with film reservoirs for delivering CAP transdermally. HFMNs were manufactured using poly(vinyl pyrrolidone) K-29/32 (PVP K-29/32), poly(vinyl alcohol) (PVA), and citric acid anhydrous. CAP was formulated into DMNs and film reservoirs (FD). CAP-loaded DMNs were manufactured using PVP K-29/32 and PVA. Meanwhile, CAP-containing FDs were prepared using PVP K-29/32, PVP K-90, and glycerol. The manufactured polymeric microneedles were evaluated in terms of their mechanical properties and the ability to deliver CAP in an in vitro study using Franz diffusion cells. Based on the in vitro studies, both HFMNs integrated with FDs (FD-1) and DMN-1 successfully delivered the CAP with the cumulative amount of drug permeated were 9.90 ± 0.31 mg and 7.49 ± 0.17 mg, respectively. Results revealed that both HFMN and DMN were able to deliver more than 50 % of CAP loaded. This research presents a novel insight, for the first time, by showcasing DMNs and HFMN as promising approaches for delivering CAP transdermally.

Foams Set a New Pace for the Release of Diclofenac Sodium.

Medicated foams have emerged as promising alternatives to traditional carrier systems in pharmaceutical research. Their rapid and convenient application allows for effective treatment of extensive or hirsute areas, as well as sensitive or inflamed skin surfaces. Foams possess excellent spreading capabilities on the skin, ensuring immediate drug absorption without the need for intense rubbing. Our research focuses on the comparison of physicochemical and biopharmaceutical properties of three drug delivery systems: foam, the foam bulk liquid, and a conventional hydrogel. During the development of the composition, widely used diclofenac sodium was employed. The safety of the formulae was confirmed through an in vitro cytotoxicity assay. Subsequently, the closed Franz diffusion cell was used to determine drug release and permeation in vitro. Ex vivo Raman spectroscopy was employed to investigate the presence of diclofenac sodium in various skin layers. The obtained results of the foam were compared to the bulk liquid and to a conventional hydrogel. In terms of drug release, the foam showed a rapid release, with 80% of diclofenac released within 30 min. In summary, the investigated foam holds promising potential as an alternative to traditional dermal carrier systems, offering faster drug release and permeation.

Development of favipiravir dry powders for intranasal delivery: An integrated cocrystal and particle engineering approach via spray freeze drying

The therapeutic potential of pharmaceutical cocrystals in intranasal applications remains largely unexplored despite progressive advancements in cocrystal research. We present the application of spray freeze drying (SFD) in successful fabrication of a favipiravir-pyridinecarboxamide cocrystal nasal powder formulation for potential treatment of broad-spectrum antiviral infections. Preliminary screening via mechanochemistry revealed that favipiravir (FAV) can cocrystallize with isonicotinamide (INA), but not nicotinamide (NCT) and picolinamide (PIC) notwithstanding their structural similarity. The cocrystal formation was characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy, and unit cell determination through Rietveld refinement of powder X-ray analysis. FAV-INA crystalized in a monoclinic space group P21/c with a unit cell volume of 1223.54(3) Å3, accommodating one FAV molecule and one INA molecule in the asymmetric unit. The cocrystal was further reproduced as intranasal dry powders by SFD, of which the morphology, particle size, in vitro drug release, and nasal deposition were assessed. The non-porous flake shaped FAV-INA powders exhibited a mean particle size of 19.79 ± 2.61 μm, rendering its suitability for intranasal delivery. Compared with raw FAV, FAV-INA displayed a 3-fold higher cumulative fraction of drug permeated in Franz diffusion cells at 45 min (p = 0.001). Dose fraction of FAV-INA deposited in the nasal fraction of a customized 3D-printed nasal cast reached over 80 %, whereas the fine particle fraction remained below 6 % at a flow rate of 15 L/min, suggesting high nasal deposition whilst minimal lung deposition. FAV-INA was safe in RPMI 2650 nasal and SH-SY5Y neuroblastoma cells without any in vitro cytotoxicity observed. This study demonstrated that combining the merits of cocrystallization and particle engineering via SFD can propel the development of advanced dry powder formulations for intranasal drug delivery.

MALDI-TOF imaging analysis of benzalkonium chloride penetration in ex vivo human skin.

Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that is used as an antiseptic. BZK is classified as a quaternary ammonium compound composed of molecules of several alkyl chains of differing lengths, that dictate its effectiveness towards different microbes. As a result, BZK has become one of the most used preservatives in antibacterial solutions. Despite its widespread use, it is not clear whether BZK penetrates human skin. To answer this question, BZK treated skin was analyzed using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry imaging. Solutions containing BZK and differing excipients, including citric acid, caprylyl glycol, and vitamin E, were applied ex vivo to excised human skin using Franz diffusion cells. Treated skin was embedded in gelatin and sectioned prior to MALDI-TOF imaging. BZK penetrates through the epidermis and into the dermis, and the penetration depth was significantly altered by pH and additives in tested solutions.

Preparation and Evaluation of Liposomes Containing Ethanol and Propylene Glycol as Carriers for Nicotine.

Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations. This study focused on the preparation of stable nicotine-encapsulated ethosomes. During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy. When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13 ± 1.40), smallest particle size (106.0 ± 11.0) nm, maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotineencapsulated ethosomes (ethanol: PG = 5:5, w/w) were an efficient and stable transdermal delivery system. The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.

Triptolide-Loaded Solid Lipid Nanogel: Preparation and In-Vitro Evaluation

In order to topically deliver triptolide (TPL), we sought to develop and characterize solid lipid nano-particles based gel (SLNs-gel) before we investigated its inhibitory activity on HaCaT cells. Preparation of TPL-loaded SLNs (TPL-SLNs) was performed with a method involving melt-emulsion ultra-sonication and solidification at low temperature. The determined characteristics of TPL-SLNs were particle size (PS), encapsulation efficiency (EE), zeta potential (ZP), microscopic mor phology and release of TPL In-Vitro. After TPL-SLNs have been formulated into gel, we used the Franz diffusion cell method to evaluate the skin permeation and penetration characteristics of TPL-SLNs-gel on rat’s skin. Imaging results showed that particles of TPL-SLNs were homogeneous and well-dispersed. Meanwhile, the PS and ZP of TPL-SLNs were 89.21 ± 9.68 nm and −41.3 ± 6.23 mV, respectively, with EE being 89.3%. Also, we observed a significant improvement in pattern of In-Vitro TPL release from TPL-SLNs compared to free TPL. Furthermore, the cumulative penetration of TPL-SLNs-gel was higher (5.28 times) compared to free TPL. Besides, TPL-SLNs-gel demonstrated substantial higher cytostatic activity on HaCaT cells comparable to both free TPL and TPL-SLNs. Altogether, it is evident that a delivery system like SLNs-gel can potentially increase the transdermal bioavailability of TPL for effective inhibition of proliferous HaCaT cells

Predicting skin permeation-enhancing effect of fixed oils using saturated to unsaturated fatty acid ratio content

Background: Transdermal drug delivery is non-invasive and advantageous as it improves patient compliance.
 Objective: This study evaluated the effect of varying ratios of saturated to unsaturated fatty acids in fixed oils on the permeation of ibuprofen across pig dorsal skin.
 Methods: The solubility of ibuprofen in soybean oil, theobroma oil, and shea butter (fixed oils) was evaluated and in vitro skin permeation studies were conducted using Franz diffusion cells.
 Results: A significant difference in permeability parameters, such as flux and effective skin permeability, in the different formulations was observed. Skin permeation depended on the ratio of saturated to unsaturated fatty acids. It also depended on the type and concentration of individual saturated and unsaturated fatty acids present in the fixed oils. The skin permeation of ibuprofen increased with an increasing ratio of palmitic acid (PA) to oleic acid (OA) concentrations. The highest flux was obtained in the theobroma oil formulation, with a PA:OA ratio of 0.78. The lowest flux was obtained in the shea butter formulation, with a PA:OA ratio of 0.09. The PA:OA ratio was 0.46 in the soybean oil formulation.
 Conclusion: These results suggest that the ratio of saturated to unsaturated fatty acids in fixed oils could be used as a model for predicting the rate of skin permeation of drugs in oil-based formulations. Depending on the desired rate of drug permeation, different combinations of the ratio of saturated to unsaturated fatty acids can be used in formulations for transdermal delivery.

Design of High-Payload Ascorbyl Palmitate Nanosuspensions for Enhanced Skin Delivery.

A high-payload ascorbyl palmitate (AP) nanosuspension (NS) was designed to improve skin delivery following topical application. The AP-loaded NS systems were prepared using the bead-milling technique, and softly thickened into NS-loaded gel (NS-G) using hydrophilic polymers. The optimized NS-G system consisted of up to 75 mg/mL of AP, 0.5% w/v of polyoxyl-40 hydrogenated castor oil (Kolliphor® RH40) as the suspending agent, and 1.0% w/v of sodium carboxymethyl cellulose (Na.CMC 700 K) as the thickening agent, in citrate buffer (pH 4.5). The NS-G system was embodied as follows: long and flaky nanocrystals, 493.2 nm in size, -48.7 mV in zeta potential, and 2.3 cP of viscosity with a shear rate of 100 s-1. Both NS and NS-G provided rapid dissolution of the poorly water-soluble antioxidant, which was comparable to that of the microemulsion gel (ME-G) containing AP in solubilized form. In an ex vivo skin absorption study using the Franz diffusion cell mounted on porcine skin, NS-G exhibited faster absorption in skin, providing approximately 4, 3, and 1.4 times larger accumulation than that of ME-G at 3, 6, and 12 h, respectively. Therefore, the high-payload NS makes it a promising platform for skin delivery of the lipid derivative of ascorbic acid.

Tocopherol succinate-loaded ethosomal gel synthesized by cold method technique: Deeper biophysical characterizations for translational application on human skin.

Tocopherols are well-known antioxidant and moisturizing agent. Tocopherol succinate (TS) are widely used in many skin products especially used in anti-aging and skin whitening product formulation. We previously reported the successful synthesis and preliminary characterizations of stable TS ethosomal gels (TSEG) (DOI: 10.1111/jocd.14907). Herein, we develop and further characterize TSEG to enhance the stability of the developed formulation with increased permeation through skin. Cold method technique was used to prepare TS ethosomes. The developed ethosomal vesicle size was 250 nm, which allowed TS to penetrate through the stratum corneum layer and act on melanocytes. For stability study was assessed by thermogravimetric analysis (TGA) by placing TSEG and unloaded/control ethosomal gel (CEG) at various temperature conditions, that is, 8°C, 25°C, 40°C, and 40°C ± 75% RH for 3 months. Organoleptic evaluation was done in terms of color, odor, and phase separation. Transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), x-ray diffraction spectroscopy (XRD), zeta potential (ZP) and particle size (PS) was used for TSEG physical characterizations. Invitro dissolution and ex-vivo permeation studies (using Franz diffusion cell) were performed for both TSEG and CEG formulations. Human women (N = 34) were used to evaluate invivo biophysical parameters including erythema, melanin, moisture content, sebum level, and skin elasticity. Developed formulation was highly thermostable during the 3 months. Erythema, melanin, and sebum level decreased while marked improvement (p < 0.05) in moisture content and elasticity have been observed for the developed TSEG. The developed TSEG formulation was found to be efficient, safe (no adverse effects observed), stable (at least for 3 months), and easy to use for topical application with improved skin complexation and skin integrity.

Preparation and characterization of novel mirabegron salts for sustaining dissolution and improving diffusion/permeability

Overactive bladder (OAB) is a disturbing and distressing condition associated with severe adverse consequences, such as depression, social isolation and participation restriction. Mirabegron (Mira.), used for the treatment of OAB is a BCS class-III drug that displays inconsistent bioavailability upon oral administration depending on dose, gender, and food intake. The present investigation aimed to synthesize sustained release/slow dissolving salts of Mira. to overcome its food intake dependent erratic bioavailability and to improve its permeability. The solvent evaporation method was used to prepare novel slow dissolving salts of Mira. by reacting it with various long-chain fatty acids (stearic acid, palmitic acid, myristic acid, and lauric acid). The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies suggested the genesis of a new crystalline phase due to a reaction between Mira. and fatty acids. Fourier-transform infrared spectroscopy (FTIR) and 1H Nuclear magnetic resonance (NMR) studies confirmed the transfer of proton between the primary amine group (-NH2) of Mira. and carboxylic acid group (-COOH) of fatty acids and thus the formation of salts. The prepared salts have significantly slower dissolution than Mira. in 6.8 pH phosphate buffer. The equilibrium solubility of prepared salts were lower than Mira in 6.8 pH phosphate buffer and water. The in-vitro diffusion study using the Franz diffusion cell proved better permeability of the prepared salts compared to Mira.

Immunopotentiating Polyphosphazene Delivery Systems: Supramolecular Self-Assembly and Stability in the Presence of Plasma Proteins.

Studies on the biological performance of nanomedicines have been increasingly focused on the paradigm shifting role of the protein corona, which is imminently formed once the formulation is placed in a complex physiological environment. This phenomenon is predominantly studied in the context of protein adsorption science, while such interactions for water-soluble systems remain virtually unexplored. In particular, the importance of plasma protein binding is yet to be understood for pharmaceuticals designed on the basis of supramolecular architectures, which generally lack well-defined surfaces. Water-soluble ionic polyphosphazenes, clinically proven immunoadjuvants and vaccine delivery vehicles, represent an example of a system that requires supramolecular coassembly with antigenic proteins to attain an optimal immunopotentiating effect. Herein, the self-assembly behavior and stability of noncovalently bound complexes on the basis of a model antigen─hen egg lysozyme─and polyphosphazene adjuvant are studied in the presence of plasma proteins utilizing isothermal calorimetry, asymmetric flow field flow fractionation, dynamic light scattering, and size exclusion chromatography methods. The results demonstrate that although plasma proteins, such as human serum albumin (HSA), show detectable avidity to polyphosphazene, the strength of such interactions is significantly lower than that for the model antigen. Furthermore, thermodynamic parameters indicate different models of binding: entropy driven, which is consistent with the counterion release mechanism for albumin versus electrostatic interactions for lysozyme, which are characterized by beneficial enthalpy changes. In vitro protein release experiments conducted in Franz diffusion cells using enzyme-linked immunoassay detection suggest that the antigen-adjuvant complex stability is not adversely affected by the presence of the most physiologically abundant protein, which confirms the importance of the delivery modality for this immunoadjuvant. Moreover, HSA shows an unexpected stabilizing effect on complexes with high antigen load─an important consideration for further development of polyphosphazene adjuvanted vaccine formulations and their functional assessment.

The Formulation of Dermato-Cosmetic Products Using Sanguisorba minor Scop. Extract with Powerful Antioxidant Capacities

There has been a significant increase in the use of botanical resources for the formulation of topical products designed for medicinal and cosmetic applications. Sanguisorba minor Scop., a botanical species, exhibits a variety of properties and has significant potential for applications in the field of cosmetics. The aim of this study was to formulate topical preparations, incorporating an extract derived from the plant S. minor Scop. comprising a combination of roots, leaves, and flowers. In the initial phase, a total of seven combinations were prepared using extracts derived from the roots, leaves, and flowers of S. minor Scop. (v/v/v). These combinations were subsequently subjected to evaluation for their antioxidant capacity using four distinct methods: 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), and Trolox equivalent antioxidant capacity (TEAC). An extract of plant organs in a ratio of 1:2:1 (v/v/v), which had a strong antioxidant capacity and demonstrated synergistic effects according to the DPPH, TEAC, and CUPRAC assays (with values of 1.58 ± 0.1, 1.18 ± 0.09, and 1.07 ± 0.07, respectively), was selected for inclusion in three dermato-cosmetic products (hydrogel, emulgel, and cream). All the prepared preparations were evaluated in terms of topical formulation attributes and organoleptic characteristics. The testing of dermato-cosmetic products included assessments of their topical formulation properties and organoleptic characteristics. The hydrogel, emulgel, and cream exhibited varying degrees of stretchability. In addition, a study was carried out to assess the in vitro release of polyphenols from the cosmetic formulations using a Franz diffusion cell system. The results showed that the emulgel containing the extract of S. minor Scop. had the highest and most significant release of polyphenols, with a release rate of 84.39 ± 1.01%. This was followed by the hydrogel and cream, which had release percentages of 80.52 ± 0.89 and 75.88 ± 0.88, respectively, over an 8 h period. Thus, for the first time in the literature, a topical cosmetic product with high antioxidant potential containing S. minor Scop. extract was developed and optimized.

Preparation and characterization of diclofenac transdermal patch using ethyl cellulose and polyvinyl alcohol by electrospinning

In recent years, the adverse effects linked to the oral administration of diclofenac, a non-steroidal anti-inflammatory drug (NSAID), have urged interest in exploring alternative administration routes, specifically transdermal drug delivery (TDD). Among the techniques emerging for creating nanoscale fibres suitable for TDD systems, electrospinning has attracted attention. The primary objective of this study was to formulate and evaluate nanofibers loaded with diclofenac diethylamine using ethylcellulose (EC) and polyvinyl alcohol (PVA) polymers. The influence of penetration enhancers, namely farnesol and nerolidol, on the properties of these fibres was investigated. Employing the electrospinning technique, nanofibers composed of EC or PVA polymers, with or without penetration enhancers, were fabricated, all maintaining a constant drug-to-polymer ratio. Mechanical strength and release kinetics from a cellophane membrane for the obtained nanofibers were investigated. A Franz diffusion cell was employed to determine the drug penetration rates through rat skin for selected fibre formulations. To gain insights into potential interactions and changes in the drug's solid state, FTIR spectroscopy, DSC, and XRD analyses were conducted. Microscopic examination unveiled that EC-based fibres exhibited homogeneity and lacked bead formations, albeit with larger diameters than other formulations. In contrast, both EC and PVA-based fibres displayed bead formations and nanometer-scale widths. The incorporation of penetration enhancers led to the production of uniform, bead-free nanofibers, with minor impacts on fiber size. EC fibres exhibited the lowest tensile strength and modulus of elasticity, but maximum flexibility. The addition of PVA and penetration enhancers contributed to enhanced fibre toughness and resistance to deformation. These alterations also positively influenced drug release rates, as observed in experiments conducted on cellophane membranes. Notably, when comparing drug release on rat skin to cellophane membranes, a slower initial release followed by a steeper slope was noted, attributed to the beneficial role of penetration enhancers on skin permeation. Analyzing results from DSC revealed the transition of the crystalline form of diclofenac diethylamine to an amorphous state within the nanofiber matrix which was also supported by XRD data. In light of these findings, electrospun nanofibers comprising a combination of EC and PVA polymers, alongside a penetration enhancer and diclofenac diethylamine, exhibit considerable promise for utilization as transdermal patches.

A bio-ionic liquid based self-healable and adhesive ionic hydrogel for the on-demand transdermal delivery of a chemotherapeutic drug.

The non-invasive nature and potential for sustained release make transdermal drug administration an appealing treatment option for cancer therapy. However, the strong barrier of the stratum corneum (SC) poses a challenge for the penetration of hydrophilic chemotherapy drugs such as 5-fluorouracil (5-FU). Due to its biocompatibility and capacity to increase drug solubility and permeability, especially when paired with chemical enhancers, such as oleic acid (OA), which is used in this work, choline glycinate ([Cho][Gly]) has emerged as a potential substance for transdermal drug delivery. In this work, we examined the possibility of transdermal delivery of 5-FU for the treatment of breast cancer using an ionic hydrogel formulation consisting of [Cho][Gly] with OA. Small angle neutron scattering, rheological analysis, field emission scanning electron microscopy, and dynamic light scattering analysis were used to characterize the ionic hydrogel. The non-covalent interactions present between [Cho][Gly] and OA were investigated by computational simulations and FTIR spectroscopy methods. When subjected to in vitro drug permeation using goat skin in a Franz diffusion cell, the hydrogel demonstrated sustained release of 5-FU and effective permeability in the order: [Cho][Gly]-OA gel > [Cho][Gly] > PBS (control). The hydrogel also demonstrated 92% cell viability after 48 hours for the human keratinocyte cell line (HaCaT cells) as well as the normal human cell line L-132. The breast cancer cell line MCF-7 and the cervical cancer cell line HeLa were used to study in vitro cytotoxicity that was considerably affected by the 5-FU-loaded hydrogel. These results indicate the potential of the hydrogel as a transdermal drug delivery vehicle for the treatment of breast cancer.

Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) as an insulin carrier in silk fibroin hydrogels for transdermal delivery via iontophoresis.

In this study, silk fibroin (SF) was utilized as the starting material to fabricate physically crosslinked hydrogels. Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) was synthesized and characterized as a drug carrier, with insulin as the model drug. PEDOT:PSS, with a high electrical conductivity of 1666 ± 49 S cm-1, interacted with insulin molecules via electrostatic interaction by replacing the dopant PSS molecules. Insulin-loaded PEDOT:PSS embedded in the SF hydrogel resulted in an increase in the degree of swelling, pore size, and mesh size of the hydrogel. In the in vitro release and release-permeation experiments, the amounts of insulin release and release-permeation were investigated using a modified Franz diffusion cell, under the effects of SF concentrations, electric fields, and pH values. The amounts of insulin release and release-permeation from the pristine SF hydrogel and the PEDOT:PSS/SF hydrogel followed the power laws with the scaling exponents close to 0.5, indicating the Fickian diffusion or the concentration gradient. Under electric fields, with or without PEDOT:PSS used as the drug carrier, the insulin amount and diffusion coefficient were shown to increase with the increasing electric field due to the electro-repulsive forces between the cathode and insulin molecules and SF chains, electroosmosis, and SF matrix swelling. The SF hydrogel and PEDOT:PSS as the drug carrier are demonstrated herein as new components in the transdermal delivery system for the iontophoretically controlled insulin basal release applicable to diabetes patients.

Scanning electrochemical microscopy for the differentiation of radical-induced degradation mechanisms in polymer electrolyte membranes.

In this work, a spatially resolved analytical method based on scanning electrochemical microscopy (SECM) to distinguish different degradation phenomena in polymer electrolyte membranes was developed. SECM was combined with a Franz diffusion cell to distinguish between radical-induced aging of a sulfonated tetrafluoroethylene based fluoropolymer-copolymer due to deactivation of the sulfonic acid groups followed by a decreased proton conductivity, and the radical-induced formation of cracks and holes in the polymer. The experiments were performed with ferrocyanide as redox mediator to detect holes and cracks, and protons (sulfuric acid) to determine the through-plane proton conductivity, respectively. A pristine Nafion™ membrane, a pristine Nafion™ membrane with an artificial pinhole and a Nafion™ membrane aged with Fenton's reagent were investigated to prove the measurement principle. It could be shown that holes and cracks can be reliably detected with this approach and discriminated from a change in proton conductivity. The presence of holes in the investigated aged membranes was confirmed by scanning electron microscopy, whereas the loss of sulfonate groups could be supported by infrared spectroscopy measurements.

3D printed personalized wound dressings using a hydrophobic deep eutectic solvent (HDES)-formulated emulgel.

Curcuminoids, known for their antibacterial, anti-inflammatory, and wound healing properties, face challenges in medical applications due to their limited water solubility, resulting in poor bioavailability and clinical efficacy. This study introduces a novel approach to formulating 3D printing ink for personalized wound dressings by utilizing hydrophobic deep eutectic solvents (HDES) to incorporate poorly water-soluble compounds from Curcuma longa (i.e., curcuminoids and ar-turmerone) into hydrogels. The use of HDES, comprising either acetic acid or octanoic acid combined with menthol in a 2 : 1 molar ratio, significantly improved the solubility of curcuminoid derivatives and ar-turmerone by approximately 10 to 600 times, depending on the intrinsic chemical polarities of each compound, compared to conventional extraction solvents (i.e., ethanol and water). By formulating an emulgel using HDES as the oil phase in a gelatin methacryloyl (GelMA) solution stabilized by a biocompatible surfactant, we achieved a 3D biocompatible printing ink with preserved rheological characteristics, enabling the production of personalized wound dressings using a custom-designed, syringe-based 3D printer. The emulgel constructs exhibited regulated swelling profiles, prolonged release of curcuminoids over 60 days as monitored by a Franz cell diffusion assay, and promoted human dermal fibroblast proliferation in vitro. Additionally, the emulgel components worked synergistically with curcuminoids to significantly enhance anti-biofilm activity against Staphylococcus aureus, offering an effective strategy to prevent wound infections. Our findings have demonstrated, for the first time, the formulation of biochemical ink for 3D printing harnessing HDES, providing a new pathway for developing advanced wound dressings with relatively high concentrations of poorly soluble plant bioactive compounds tailored for chronic wound management.

Acanthus mollis Formulations for Transdermal Delivery: From Hydrogels to Emulsions.

Topical formulations of Acanthus mollis L. leaf and the optimization of the release of their active compounds and their topical bioavailability were investigated for the first time. In vitro, the release of active compounds from three formulations-an oil-in-water cream and two hydrogels (Carbopol 940 and Pluronic F-127)-was determined using Franz diffusion cells. Detection and quantification of the compounds was performed via high-performance liquid chromatography with a photodiode array (HPLC-PDA). DIBOA, a bioactive compound of this medicinal plant, exhibited release kinetics of the Weibull model for the Carbopol and Pluronic F-127 formulation, identifying it as a potential active agent to optimize the topical distribution of the formulations. The implications extend to applications in inflammation treatment and tyrosinase inhibition, suggesting that it can make a significant contribution to addressing skin conditions, including melanoma and various inflammatory diseases.

Development of Topical Formulations Containing 20% of Coated and Uncoated Zinc Oxide Nanoparticles: Stability Assessment and Penetration Evaluation by Reflectance Confocal Laser Microscopy

The introduction of zinc oxide nanoparticles (ZnOn) in sunscreens solved the issue of poor spreadability of these formulations, which often left a white film on the skin. However, safety concerns have arisen regarding the topical application of ZnOn. Some studies employed commercial sunscreens to address the safety issues of the topical application of ZnOn; however, commercial formulations are often complex and contain a wide range of ingredients that could attenuate the potential damage caused by the ZnOn. Therefore, in this study we aimed to develop a simple stable formulation containing 20% of coated and uncoated ZnOn, characterize the formulations and the nanoparticles, and assess the skin penetration in a Franz diffusion cell. The Feret’s diameter for the uncoated and coated ZnOn was 137 nm and 134 nm, respectively. For the uncoated ZnOn the hydrodynamic size in water was 368 nm and for the coated ZnOn, the average hydrodynamic size in ethyl acetate was 135 nm. The incorporation of ZnOn led to formulations more consistent and easier to spread, as suggested by the lower work of shear and higher values of firmness, cohesiveness, consistency and index of viscosity compared with the vehicle. The stability assessment at 45 °C suggested that the formulations containing the ZnOn were stable for 30 days and the vehicle was stable for 90 days. The assessment of the skin penetration by reflectance confocal laser microscopy indicated that the ZnOn did not permeate into the deepest layers of the skin, but accumulated on the skin furrows, hair and hair follicles.

Magnetic nano composites for gallic acid delivery

A new magnetic layered double hydroxide (MLDH) composed of Fe, Mg, and Al was designed to improve gallic acid delivery to breast tumors. The metals formed the octahedrons within the layers, while the gallate ions were dissolved in the aqueous interlayer space. The drug loading was 30 %, determined with UV/Vis spectrophotometry. The material exhibited superparamagnetic behavior with a saturated magnetization of 5.5 emu/gr. This magnetic property enables the compound to be directed towards the therapeutic target using an external magnetic field, while the superparamagnetic attribute prevents the material from remaining magnetized in the body after the external magnetic field is removed. The diameter of the composites, measured from TEM images, was 110 nm: small enough for systemic circulation. For comparison, a conventional layered double hydroxide composed of Mg and Al was loaded with gallic acid and impregnated with Fe3O4 magnetic nanoparticles (LDH-NP). The drug loading was slightly lower (23 %), and the material demonstrated a combination of superparamagnetic and ferromagnetic behavior. However, the saturated magnetization was higher, 15 emu/gr for the superparamagnetic-like component and 13 emu/gr for the ferromagnetic-like component. From TEM images, the diameter of the composites was 57 nm. Drug release was studied with Franz diffusion cells. Both systems showed fast release at the lysosomal pH (4.8), but the MLDH avoids the release at the blood pH (7.4) more than the LDH-NP. Lastly, the systems were tested against breast cancer cells. After 48 h, the new composite demonstrated a 77 % reduction in cell viability, while the conventional composite impregnated with NPs showed a 66 % reduction. The designed Fe/Mg/Al magnetic nano composite loaded with gallic acid is easier to manufacture and holds promise for breast cancer treatments.