Permeation Studies Research Articles

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action.Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42cm/h for rat skin, 13.64cm/h for mice skin, and 18.97cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Reusable and effective polyacrylic membranes for mecoprop and bentazon extractions

This study introduces reusable polyacrylic membranes, fabricated from commercially available monomers (1-vinyl-2-pyrrolidone and methylmethacrylate), as a promising approach for pesticide extraction. These membranes effectively remove the commonly used herbicides mecoprop (RE ≈ 99%) and bentazon (RE ≈ 95%) at low concentrations, which pose water contamination risks due to their water-soluble properties and leaf-level sorption. The membranes exhibit excellent manageability and resistance, allowing for safe handling without personal protective equipment. Additionally, the material is environmentally friendly and can be washed and reused for at least 4 cycles without a significant decrease in performance. Characterization techniques, including NMR, TGA, DSC, mechanical testing, N2 adsorption, and FTIR analysis, were used to investigate properties and assess the influence of the polymeric composition. The study focused on examining the lateral charged aminoethyl groups, which play a crucial role in sorbent-sorbate interactions. Sorption kinetics, isotherms, and permeation studies provided insights into the removal mechanism, efficiency, and permeability coefficients, revealing hydrophobic–hydrophobic interactions between the pesticides and the polymer. Molecular dynamics simulations revealed a scorpion-like conformation of the macromolecular chains surrounding the pesticides. These findings support the hydrophobic nature of the extraction mechanism and highlight the significant role of charged aminoethyl groups in facilitating this process.

Antibacterial Activity and Action Mechanism of Bacteriocin Paracin wx7 as a Selective Biopreservative against Vancomycin-Resistant Enterococcus faecalis in Fresh-Cut Lettuce

Fresh-cut vegetables are widely consumed, but there is no food preservative available to selectively inhibit vancomycin-resistant E. faecalis, which is a serious health menace in fresh-cut vegetables. To develop a promising food biopreservative, a bacteriocin, paracin wx7, was synthesized, showing selective inhibition against E. faecalis with MIC values of 4–8 μM. It showed instant bactericidal mode within 1 h at high concentrations with concomitant cell lysis against vancomycin-resistant E. faecalis. Its lethal effect was visualized in a dose-dependent manner by PI/SYTO9 staining observation. The results of an in vivo control experiment carried out on E. faecalis in fresh-cut lettuce showed that 99.97% of vancomycin-resistant E. faecalis were dead after 64 μM paracin wx7 treatment for 7 days without influencing total bacteria. Further, the action mechanism of paracin wx7 was investigated. Confocal microscopy showed that paracin wx7 was located both on the cell envelope and in cytoplasm. For the cell envelope, the studies of membrane permeability using SYTOX Green dyeing and DNA leakage revealed that paracin wx7 damaged the membrane integrity of E. faecalis. Simultaneously, it exhibited membrane depolarization after analysis using DiSC3(5). Damage to the cell envelope resulted in cell deformation observed by scanning electron microscopy. On entering the cytoplasm, the paracin wx7 induced the production of endogenous reactive oxygen species.

Using Polymers as Crystal Inhibitors to Prevent the Crystallization of the Rotigotine Patch

This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/w). SEM and XRD analysis revealed that the Soluplus and Soluplus-TPGS groups with a high concentration (80%, w/w) of ROT could be stored at room temperature for at least 90 days without crystallization. Moreover, the crystallization nucleation time and growth rate were utilized to assess the ability of Poloxamer 188, Soluplus, and TPGS to hinder the formation of ROT crystals and slow down its crystallization rate. Molecular docking results elucidated the intermolecular forces between ROT and different polymers, revealing their mechanisms for crystal inhibition. The ROT-Soluplus-TPGS combination exhibited the lowest binding free energy (−5.3 kcal/mol), indicating the highest binding stability, thereby effectively reducing crystal precipitation. In vitro skin permeation studies demonstrated that ROT patches containing crystal inhibitors exhibited promising transdermal effects. With increasing ROT concentration, the cumulative drug permeation substantially increased, while the lag time was notably reduced. This study offers novel insights for the development of ROT patches.

Chitosan-based buccal mucoadhesive bilayer tablets enhance the bioavailability of tizanidine hydrochloride by bypassing the first-pass metabolism

Tizanidine hydrochloride (TZN) is an antimuscarinic agent used in the treatment of pain-related spasms, multiple sclerosis, and stroke-related spasticity. It has low oral bioavailability (40 %) due to excessive first-pass metabolism in the liver. The aim of this project was to enhance the systemic bioavailability of TZN by developing buccal mucoadhesive bilayer tablet formulations using chitosan salts with molecular weights of 136 kDa (7 cP) and 169 kDa (10 cP). Structural characterisation of chitosans and their salts was performed by FTIR, 1H NMR, DSC, TGA, and XRD analyses. Soluble chitosan salts, chitosan glutamate and chitosan chloride, for the adhesive layer, and insoluble ethyl cellulose for the impermeable backing layer were selected as polymers to fabricate the buccal tablets by direct compression method. The tablets containing TZN demonstrated high swelling and good mucoadhesion characteristics as well as released all the drug within 8 h. While TC10, formulated with 10 cP chitosan chloride, showed the highest swelling properties, TG10, prepared with 10 cP chitosan glutamate, exhibited the highest mucoadhesion. Chitosan glutamate tablets (TG7 and TG10) demonstrated better mucoadhesive characteristics and stability than chitosan chloride ones (TC7 and TC10) in the buccal medium based on the results of swelling and drug release studies. The permeability studies performed by Franz diffusion cell demonstrated that the amount of TZN passing through the bovine buccal mucosa was between 13.4 and 14.4 %. Stability studies conducted at 5 ± 2 °C, 25 ± 2 °C and 40 ± 2 °C for 6 months showed that no changes in the content uniformity and pH were observed. The in vivo comparative bioavailability studies in female New Zealand rabbits were performed and TZN-containing buccal mucoadhesive bilayer tablets fabricated with both chloride (TC10) and glutamate (TG10) salts of chitosan demonstrated three times higher bioavailability than the commercial TZN product (Sirdalud® oral tablet) administered by the gastrointestinal route.

P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations’ potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

Effect of chemical penetration enhancers on the transdermal delivery of olanzapine in human skin in vitro

This research study involves the development of an olanzapine (OLZ) formulation using various chemical penetration enhancers (CPEs) for transdermal delivery. The aim of this study was to obtain the initial data needed about the effects of various CPEs on the skin permeation of OLZ. The effects of the selected CPEs were examined by studying the permeation profiles of OLZ from formulations applied to human cadaver skin samples. A control formulation of OLZ in propylene glycol (PG) was prepared and compared against formulations containing chemical penetration enhancers. Five different CPEs (oleic acid (OA), cineole (Cin), isopropyl alcohol (IPA), Tween 80 (T80), and N-methyl pyrrolidone (NMP)) at 5% w/w were individually added to the formulation containing OLZ in PG. The in vitro permeation study was carried out using vertical Franz diffusion cells mounted with human cadaver skin. Samples from the receptor compartment of the cell were collected at 2 h, 4 h, 8 h, 12 h, and 24 h at room temperature. The amount (µg/cm2) of permeated drug (OLZ) was measured using a validated HPLC method, and the percentage (%) of OLZ permeated was calculated. Based on the data obtained, different CPEs were found to have a significant impact on OLZ permeability compared to the control formulation. The most effective chemical penetration enhancer was shown to be 5% w/w OA with a 3.3-fold increase in enhancement ratio (ER). The rank of order for the highest concentration of OLZ permeated from each of CPE containing formulation was as follows: OA > Cin > IPA > T80 > NMP. The most effective chemical penetration enhancer was OA but the cytotoxic study using human fibroblast cells suggests that OA may not be safe due to its cytotoxic effects.

Berberine HCl and diacerein loaded dual delivery transferosomes: Formulation and optimization using Box-Behnken design

Introduction: Berberine is a poorly water-soluble alkaloid compound showing significant anti-inflammatory characteristics. It reduces the levels of pro-inflammatory and inflammatory cytokines, including tumour necrosis factor (TNF-????, IFN-????) and interleukin (IL-23, IL-12, and IL-23). Diacerein significantly reduces the splenomegaly associated with psoriasis. It downregulates the production of TNF-α and IL-12. Method: This study reported the development of transferosomes containing berberine HCl and diacerein using a film hydration method followed by optimization using a Box-Behnken design. Sodium deoxycholate was used as an edge activator. The impact of independent variables (amount of phosphatidylcholine, amount of edge activator, and sonication cycles) on dependent variables (particle size and entrapment efficiency) was examined. The optimized formulation was characterized for polydispersity index, vesicle size, entrapment efficiency, ζ potential, spectral analysis like Fourier transform infrared, thermal analysis, X-ray diffraction, deformability, transmission electron microscopy, antioxidant assay, in-vitro release, and ex-vivo skin permeation studies. Results: The optimized formulation had a particle size of 110.90±2.8 nm with high entrapment efficiency (89.50±1.5 of berberine HCl and 91.23±1.8 of diacerein). Deformability, polydispersity index, ζ potential, and antioxidant activity of the optimized formulation were 2.44, 0.296, -13.3, and 38.36 %, respectively. Optimized transferosomes exhibited 82.093±0.81 % and 85.02±3.81 % release of berberine HCl and diacerein after 24 h of dissolution study. The transdermal flux of optimized formulation was 0.0224 µg cm-2 h-1 (2.24 cm h-1 permeation coefficient) and 0.0462 µg cm-2 h-1 (4.62 cm h-1 permeation coefficient), respectively, for berberine HCl and diacerein. Raman analysis of treated pig skin confirmed that the transferosomes can permeate the skin. No change in the skin condition or irritation was observed in BALB/c mice. Formulation stored at 4 and 25±2 °C / 60±5 % relative humidity was stable for 3 months. Conclusions: Thus, the results demonstrated successful optimization of the transferosomes for the efficient topical delivery of berberine HCl and diacerein in the effective management of psoriasis.

3D DLP-printed cannabinoid microneedles patch and its pharmacokinetic evaluation in rats.

The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system. CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile. Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P < .0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P < .05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control). Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system.

Tailoring of Bilosomal Nanogel for Augmenting the Off-Label Use of Sildenafil Citrate in Pediatric Pulmonary Hypertension.

Pediatric pulmonary hypertension is a serious syndrome with significant morbidity and mortality. Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension. In this study, bile salt-stabilized nanovesicles (bilosomes) were screened for their efficacy to enhance the transdermal delivery of the phosphodiesterase type 5 inhibitor, sildenafil citrate, in an attempt to augment its therapeutic efficacy in pediatric pulmonary hypertension. A response surface methodology was implemented for fabricating and optimizing a bilosomal formulation of sildenafil (SDF-BS). The optimized SDF-BS formulation was characterized in terms of its entrapment efficiency (EE), zeta potential, vesicle size, and in vitro release profile. The optimized formula was then loaded onto hydroxypropyl methyl cellulose (HPMC) hydrogel and assessed for skin permeation, in vivo pharmacokinetics, and pharmacodynamic studies. The optimized SDF-BS showed the following characteristic features; EE of 88.7 ± 1.1%, vesicle size of 185.0 + 9.2 nm, zeta potential of -20.4 ± 1.1 mV, and efficiently sustained SDF release for 12 h. Skin permeation study revealed a remarkable improvement in SDF penetration from bilosomal gel compared to plain SDF gel. In addition, pharmacokinetic results revealed that encapsulating SDF within bilosomal vesicles significantly enhanced its systemic bioavailability (∼3 folds), compared to SDF oral suspension. In addition, pharmacodynamic investigation revealed that, compared to plain SDF gel or oral drug suspension, SDF-BS gel applied topically triggered a significant elevation (p < 0.05) in cGMP serum levels, underscoring the superior therapeutic efficacy of SDF-BS gel. Conclusively, bilosomes can be viewed as a promising nanocarrier for transdermal delivery of SDF that would grant higher therapeutic efficiency while alleviating the limitations encountered with SDF oral administration.

Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin.

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (Smix) of Cremophore® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low Smix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin.

Hyaluronic acid-oleylamine and chitosan-oleic acid conjugate-based hybrid nanoparticle delivery via. dissolving microneedles for enhanced treatment efficacy in localized breast cancer

Microneedle technology offers a minimally invasive treatment strategy to deliver chemotherapeutics to localized tumors. Amalgamating the surface functionalized nanoparticles with microneedle technology can potentially deliver drugs directly to tumors and subsequently target cancer cells via, overexpressed receptors on the cell surface, thereby enhancing the treatment efficacy while reducing side effects. Here, we report cetuximab anchored hyaluronic acid-oleylamine and chitosan-oleic acid-based hybrid nanoparticle (HA-OA/CS-OA NPT)-loaded dissolving microneedles (MN) for targeted delivery of cabazitaxel (CBT) in localized breast cancer tumor. The HA-OA/CS-OA NPT was characterized for their size, surface charge, morphology, physicochemical characteristics, drug release behavior, and in vitro anti-cancer efficacy. The HA-OA/CS-OA NPT were of ~125 nm size, showed enhanced cytotoxicity and cellular uptake, and elicited a superior apoptotic response against MDA-MB-231 cells. Subsequently, the morphology and physicochemical characteristics of HA-OA/CS-OA NPT-loaded MN were also evaluated. The fabricated microneedles were of ~550 μm height and showed loading of nanoparticles equivalent to ~250 μg of CBT. The ex vivo skin permeation study revealed fast dissolution of microneedles upon hydration, while the drug permeation across the skin exhibited ~4-fold improvement in comparison to free drug-loaded MN. In vivo studies performed on DMBA-induced breast cancer in female SD rats showed a marked reduction in tumor volume after administration of drug and nanoparticle-loaded microneedles in comparison to intravenous administration of free drug. However, the HA-OA/CS-OA NPT-MN showed the highest tumor reduction and survival rate, with the lowest body weight reduction in comparison to other treatment groups, indicating its superior efficacy and low systemic toxicity. Overall, the dissolving microneedle-mediated delivery of targeted nanoparticles loaded with chemotherapeutics offers a superior alternative to conventional intravenous chemotherapy.

Enhancing hydrogen separation efficiency: Insights from the permeability study of nickel-based composite membranes

This research aims to validate the capability of composite nickel-based membranes in separating hydrogen and to examine how multi-layer deposits influence the density of the nickel film. The study evaluated the hydrogen permselectivity of the membranes for both single gases (H2, N2) and binary mixtures over a temperature range from 25 °C to 700 °C. The findings revealed that the thickness of the nickel layer (ranging from 2 μm to 37 μm) and its adhesion to the support material affected the hydrogen transport through the films. Increasing the number of electroless plating treatments and the nickel thickness on γ-alumina and α-alumina tubular supports resulted in decreased hydrogen permeance but improved hydrogen selectivity. This was attributed to the enhanced recovery of the γ-alumina support and efficient filling of α-alumina support pores, depending on the membrane type. The study identified multiple mechanisms contributing to hydrogen transport, including surface diffusion, Knudsen diffusion at lower temperatures (<300 °C), and activated diffusion processes at higher temperatures (>300 °C). At 700 °C, for a Ni/0.8 μm-α-Al2O3 membrane with a 37 μm nickel film, the hydrogen permeance for single gases was 5.8 × 10−8 mol/m2 s Pa (189 GPU: gas permeance unit) with an ideal selectivity of 199 towards N2. It was 7.3 × 10−8 mol/m2 s Pa (238 GPU) for gas mixtures with an H2/N2 separation factor of 148. These results suggest that these membranes are particularly effective at high temperatures, emphasizing their potential for hydrogen separation applications and positioning them as promising materials for further development in this field.

BBD assisted in-situ nanoliposomes of esculin hydrate via intranasal delivery for the amelioration of Parkinson's disease

The objective of this research was to develop and optimise esculin Hydrate loaded nanoliposomes (ESH-NLs). The nanoliposomes were prepared by solvent evaporation method and optimized using a three-factor, three-level Box-Behnken design. Phospholipid 90G (X1), cholesterol (X2), and sonication time (X3) were used as independent variables, and their effects on vesicle size (Y1), entrapment efficiency (Y2), and Polydispersity index (Y3) were observed. The opt-ESH-NLs were further characterised for in-vitro drug release, DPPH assay, confocal laser scanning microscopy, and ex-vivo permeation. Opt-ESH-NLs had a vesicle size of 88.36 nm, a PDI of 0.06, an entrapment efficiency of 94.22 ± 0.93 %, and a drug release of 76.776 ± 1.127 %. Compared to standard ascorbic acid, the antioxidant activity was found to be 78.52 ± 0.148 %. Ex-vivo permeation studies revealed that opt-ESH-NLs had significantly enhanced permeation (79.484 ± 0.754 %) compared to ESH suspension (38.326 ± 1.279 %). Pharmacokinetic study revealed that opt-ESH-NLs when compared with Oral ESH suspension had a significant bioavailability in Brain as compared to plasma. The stability study of nanoliposomes at 4 °C reveals there is no significant change in the formulation. It was concluded that opt-ESH-NLs is a promising and effective formulation for intranasal administration for direct delivery of drug in the brain for amelioration of PD.

Multifunctional Ionic Hydrogel-Based Transdermal Delivery of 5-Fluorouracil for the Breast Cancer Treatment.

Transdermal drug delivery systems (TDDS) are a promising and innovative approach for breast cancer treatment, offering advantages such as noninvasiveness, potential for localized and prolonged drug delivery while minimizing systemic side effects through avoiding first-pass metabolism. Utilizing the distinctive characteristics of hydrogels, such as their biocompatibility, versatility, and higher drug loading capabilities, in the present work, we prepared ionic hydrogels through synergistic interaction between ionic liquids (ILs), choline alanine ([Cho][Ala]), and choline proline ([Cho][Pro]) with oleic acid (OA). ILs used in the study are biocompatible and enhance the solubility of 5-fluorouracil (5-FU), whereas OA is a known chemical penetration enhancer. The concentration-dependent (OA) change in morphological aggregates, that is, from cylindrical micelles to worm-like micelles to hydrogels was formed with both ILs and was characterized by SANS measurement, whereas the interactions involved were confirmed by FTIR spectroscopy. The hydrogels have excellent mechanical properties, which studied by rheology and their morphology through FE-SEM analysis. The in vitro skin permeation study revealed that both hydrogels penetrated 255 times ([Cho][Ala]) and 250 times ([Cho][Pro]) more as compared to PBS after 48 h. Those ionic hydrogels exhibited the capability to change the lipid and keratin arrangements within the skin layer, thereby enhancing the transdermal permeation of the 5-FU. Both ionic hydrogels exhibit excellent biocompatibility with normal cell lines (L-132 cells) as well as cancerous cell lines (MCF-7 cells), demonstrating over 92% cell viability after 48 h in both cell lines. In vitro, the cytotoxicity of the 5-FU-loaded hydrogels was evaluated on MCF-7 and HeLa cell lines. These results indicate that the investigated biocompatible and nontoxic ionic hydrogels enable the transdermal delivery of hydrophilic drugs, making them a viable option for effectively treating breast cancer.

Formulation Development of Medicated Chewing Gum by Direct Compression utilizing the SeDeM Diagram Expert System

The main objective of this study was to prepare and characterize the MCG of Ondan HCl which helps to improve the effectivity of the drug and to investigate the applicability of the SeDeM system for the formulation of MCG. The Ondan HCl was formulated into directly compressed MCG utilizing the SeDeM Diagram Expert System. The MCG was optimized using 32 factorial design. Performance evaluation was carried out by evaluating different parameters. Statistical analysis showed that micromeritic properties were improved after inclusion of appropriate excipient in optimum amount. In-vitro drug release study showed 90.01% drug release whereas ex vivo buccal permeation study exhibited significant drug permeation within 15 min indicating its potential for increasing bioavailability. It was concluded that various characteristics of powder material at pre formulation level can be successfully predicted by SeDeM diagram expert system. The developed medicated chewing gum is more effective than mouth dissolving and conventional tablet formulation.&#x0D; Keywords: Ondansetron HCl; Medicated chewing gum; direct compression; SeDeM diagram expert system.

Reviewing the Rich History of Fibrin Clot Research with a Focus on Clinical Relevance.

Fibrin, described on a single-lens microscopy for the first time by Malpighi in 1666 and named by de Fourcroy, has been extensively studied by biochemists, biophysicists, and more recently by clinicians who recognized that fibrin is the major component of most thrombi. Elucidation of key reactions leading to fibrin clot formation in the 1950s and 1960s grew interest in the clinical relevance of altered fibrin characteristics. Implementation of scanning electron microscopy to image fibrin clots in 1947 and clot permeation studies in the 1970s to evaluate an average pore size enabled plasma clot characterization in cohorts of patients. Unfavorably altered fibrin clot structure was demonstrated by Blombäck's group in coronary artery disease in 1992 and in diabetes in 1996. Fifteen years ago, similar plasma fibrin clot alterations were reported in patients following venous thromboembolism. Multiple myeloma was the first malignant disease to be found to lead to abnormal fibrin clot phenotype in the 1970s. Apart from anticoagulant agents, in 1998, aspirin was first shown to increase fibrin clot permeability in cardiovascular patients. The current review presents key data on the rich history of fibrin research, in particular, those that first documented abnormal fibrin clot properties in a variety of human disease states, as well as factors affecting fibrin phenotype.

An exosomal approach for oral delivery of resveratrol: Implications for inflammatory bowel disease treatment in rat model

AimsResveratrol (RSV) is a polyphenolic substance found in numerous natural products. Despite the wide range of therapeutic activities, including antioxidant and anti-inflammatory effects, the poor pharmacokinetic characteristics decrease the RSV bioavailability following oral administration. Milk-derived exosomes (MEXOs), as a class of natural nanocarriers, are promising candidates for oral drug delivery approaches. Main methodsThe current study developed RSV-loaded MEXOs to enhance the RSV oral bioavailability, introducing a suitable exosomal formulation for suppressing colon inflammation in acetic acid-induced rat models. Key findingsThe results showed a remarkable encapsulation efficiency of 83.33 %. The in vitro release profile demonstrated a good retaining capability in acidic conditions (pH 1.2) and a considerable release in a simulated duodenal environment (pH 6.8). According to the permeability study, encapsulation of RSV improved its transportation across the Caco-2 monolayer. Moreover, the in vivo and histological analysis results proved that the RSV-MEXOs formulation successfully alleviates the inflammation in colitis rat models and effectively relieves the colitis. SignificanceOur findings suggest that MEXOs should be of great attention as promising oral drug delivery vehicles for further clinical evaluations.

Formulation and In Vitro-Ex vivo Evaluation of Cannabidiol and Cannabidiol-Valine-Hemisuccinate Loaded Lipid-Based Nanoformulations for Ocular Applications

The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability.The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog.