Penetration Enhancers Research Articles

Mirtazapine loaded polymeric micelles for rapid release tablet: A novel formulation—In vitro and in vivo studies

Major depression is a prevalent disorder characterized by sadness, lack of interest or pleasure, interrupted sleep or food, and impaired concentration. Mirtazapine (MTZ), a tetracyclic antidepressant drug, is commonly used to treat moderate to severe depression. MTZ is classified as a BCS class II drug that has shown bioavailability of 50% due to extensive first-pass metabolism. The aim of this research is to develop a delivery platform with enhanced solubility and oral bioavailability of MTZ through formulating polymeric micelles modeled in a rapid release tablet. Mirtazapine loaded polymeric micelles (MTZ-PMs) were formulated to enhance the solubility. Solutol® HS 15 and Brij 58 were used as combined surfactants in a ratio of (20:1) to MTZ in addition to Transcutol® P as a penetration enhancer. The following in vitro tests were performed: particle size, PDI, zeta potential, solubility factor, stability index, and transmission electron microscopes. Afterward, MTZ-PMs were converted to dry free flowable powder through loading on the adsorptive surface of Aerosil 200; then, the powder mixture was directly compressed (MTZ-PMs-RRT) into 13 mm tablets. MTZ-PMs-RRT was further investigated using in vitro evaluation tests of the tablets, namely, weight variation, thickness, diameter, hardness, friability, disintegration time, drug content, and in vitro dissolution test, which complied with the pharmacopeial limits. The pharmacokinetic parameters of MTZ-PMs-RRT compared to Remeron® tablet were further investigated in rabbits. The results showed enhanced solubility of MTZ with improved percentage relative bioavailability to 153%. The formulation of MTZ in the form of MTZ-PMs-RRT successfully improved the solubility, stability, and bioavailability of MTZ using a simple and scalable manufacturing process.Graphical

Influence of Bile Acids on Clindamycin Hydrochloride Skin Permeability: InVitro and InSilico Preliminary Study.

Topical clindamycin formulations are widely used in clinical practice, but poor bioavailability and restricted skin penetration considerably limit their therapeutic efficacy. Penetration enhancement represents a promising and rational strategy to overcome the drawbacks of conventional topical pharmaceutical formulations. We aim to assess the influence of cholic acid (CA) and deoxycholic acid (DCA) on the permeability of clindamycin hydrochloride by performing the in vitro skin parallel artificial membrane permeability assay (skin-PAMPA) at two relevant pH values (5.5 and 6.5) and the interactions of tested substances with skin ATP-binding cassette (ABC) transporters in silico. After the incubation period, the clindamycin hydrochloride concentrations in both compartments were determined spectrophotometrically, and the apparent permeability coefficients (Papp) were calculated. Vienna LiverTox web service was used to predict the interactions of clindamycin and bile acids with potential drug transporters located in human skin. Both CA and DCA at the highest studied concentration of 100μM in the tested solutions increased the skin-PAMPA membrane permeability of clindamycin hydrochloride. This effect was more pronounced for CA and at a higher studied pH value of 6.5, which is characteristic of most dermatological indications treated with topical clindamycin preparations. Clindamycin transport may also be mediated by ABC transporters located in skin and facilitated in the presence of bile acids. The results of this study provide a solid foundation for further research directed at the improvement of topical formulations using bile acids as penetration-enhancing excipients, as well as the therapeutic efficacy of clindamycin hydrochloride.

504 - Investigator- and patient-rated local tolerability in phase 3 trials of topical roflumilast in patients with psoriasis, seborrheic dermatitis, and atopic dermatitis

Abstract Introduction Formulating a topical medication that does not irritate the skin is an important factor contributing to patient treatment adherence and satisfaction. Many topical prescription products use penetration enhancers (including propylene glycol, polyethylene glycol, and ethanol) to overcome barrier properties of the skin. However, these excipients may irritate the skin causing tolerability reactions such as burning and stinging, which can reduce patient treatment adherence. Topical roflumilast is a highly potent (Kd∼0.7 nM) phosphodiesterase 4 inhibitor formulated as a water-based cream or foam that does not contain penetration enhancers or fragrances. Objectives We present prospectively assessed investigator- and patient-rated local tolerability from Phase 3 trials of topical roflumilast for patients with psoriasis (DERMIS-1, DERMIS-2, ARRECTOR) seborrheic dermatitis (SD; STRATUM), and atopic dermatitis (AD; INTEGUMENT-1, INTEGUMENT-2). Methods Patients were randomized to apply topical roflumilast (DERMIS: 0.3% cream; ARRECTOR and STRATUM: 0.3% foam; INTEGUMENT: 0.15% cream) or vehicle once daily for 8 weeks (DERMIS, ARRECTOR, and STRATUM) or 4 weeks (INTEGUMENT). Investigators assessed local tolerability on an 8-point scale (0 [no evidence of irritation] to 7 [strong reaction spreading beyond application site]) in the clinic before investigational product (IP) application. Patients reported local tolerability on a 4-point scale (0 [none: no sensation] to 3 [severe: hot, tingling/stinging sensation that has caused definite discomfort]) in the clinic 10-15 minutes after IP application. Tolerability was also assessed by reviewing documented adverse events. Results As assessed by investigators, ≥96.5% of patients in the roflumilast-treated groups had no evidence of irritation at the application site across all trials at all timepoints. Patient-rated local tolerability was favorable and improved with treatment: across all trials, 1% of roflumilast-treated patients reported a score of 3 (severe; defined as a “hot tingling/stinging sensation that has caused definite discomfort”) after the first application (day 1) and <1% at each subsequent assessment. Rates of adverse events, including those at the application site, were low for all trials. Conclusions Roflumilast cream and foam formulations demonstrated favorable local tolerability based on investigator- and patient-rated assessments in patients with psoriasis, SD, and AD, including application to sensitive areas such as the face and intertriginous areas. ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389; ARRECTOR: NCT05028582; STRATUM: NCT04973228; INTEGUMENT-1: NCT047​73587; INTEGUMENT-2: NCT04773600.

Design, Formulation, and Evaluation of Lisinopril Mucoadhesive Buccal Patches by Using the Combination of Natural Polymers

The main objective of present investigation to formulate and evaluate mucoadhesive buccal patches of Lisinopril using solvent casting method. Sodiumalginate combined with Sodium carboxyl methyl cellulose, HPMC, and Carbopol934 in different proportions were used as a mucoadhesive polymer and Propyleneglycol used as a plasticizer as well as penetration enhancers. The formulated Buccal patches of Lisinopril were evaluated on the basis of Thickness, Weight uniformity, folding endurance, swelling Studies, Surface pH Determination, Percentage Moisture loss, Drug content Uniformity, Ex-Vivo Mucoadhesive strength, In Vitro Drug Release, Ex- vivo permeation study. By compatibility study there is no chemical interaction between drug and excipients used. All prepared buccal patches were transparent, smooth, consistent and flexible. The surface pH of all formulations was found to be almost in neutral pH and no mucosal irritation was expected. Among all the formulations, F6 showed maximum swelling index as 25.01%. The optimized formulation F6 also showed satisfactory, Mucoadhesive strength (5.1kg/cm2), drug content (98.75), and Ex-Vivo permeation (82.03%). In-Vitro drug release of optimised formulation (F6) was found to be 75.12 at the end of 8 hrs. Drug release mechanism was determined by plotting release data to Higuchi and Korsmeyer-Peppas model. All the formulations are best fitted to Korsmeyer-Peppas model and according to this model the drug releases from theses patches may be controlled by diffusion with super case-II transport.

Topical Ophthalmic Liposomes Dual-Modified with Penetratin and Hyaluronic Acid for the Noninvasive Treatment of Neovascular Age-Related Macular Degeneration.

Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.

Formulation and Optimization of Nanoemulsions Loaded with Gamma−Aminobutyric Acid (GABA) for Dermatological Application: Assessing Skin Permeation and Penetration Enhancement

Gamma−aminobutyric acid (GABA) presents several potential skin benefits, but its water−soluble nature poses challenges for effectively penetrating the skin to produce its effects. This research aimed to improve GABA’s skin penetration and availability by employing a nanoemulsion formulation, both with and without the aid of the penetration enhancer 1,8−cineole. Using a high−pressure homogenizer, an oil−in−water nanoemulsion was created, and its size and distribution were analyzed. The stability of these nanoemulsions was tested under various conditions, revealing their resilience over six months, even at elevated temperatures of 40 °C. In vitro tests on pig skin showed that GABA−loaded nanoemulsions, particularly those without the enhancer, demonstrated a nearly 2.89−fold increase in skin permeation compared to the solution form. Moreover, the addition of the enhancer amplified this effect, resulting in over a 3.37−fold increase in skin permeation compared to the solution. These results emphasize the potential of nanoemulsion formulations as effective tools for enhancing GABA’s skin permeation and availability, potentially expanding its use in dermatological applications. Further exploration and research are necessary to fully exploit GABA’s capabilities in supporting skin health and wellness.

Effect of Penetration Enhancer on the Structure of Stratum Corneum: On-Site Study by Confocal Polarized Raman Imaging.

Keratin and lipid structures in the stratum corneum (SC) are closely related to the SC barrier function. The application of penetration enhancers (PEs) disrupts the structure of SC, thereby promoting infiltration. To quantify these PE-induced structural changes in SC, we used confocal Raman imaging (CRI) and polarized Raman imaging (PRI) to explore the integrity and continuity of keratin and lipid structures in SC. The results showed that water is the safest PE and that oleic acid (OA), sodium dodecyl sulfate (SDS), and low molecular weight protamine (LMWP) disrupted the ordered structure of keratin, while azone and liposomes had less of an effect on keratin. Azone, OA, and SDS also led to significant changes in lipid structure, while LMWP and liposomes had less of an effect. Establishing this non-invasive and efficient strategy will provide new insights into transdermal drug delivery and skin health management.

A Chromosome-Level Genome Assembly of the Non-Hematophagous Leech Whitmania pigra (Whitman 1884): Identification and Expression Analysis of Antithrombotic Genes.

Despite being a non-hematophagous leech, Whitmania pigra is widely used in traditional Chinese medicine for the treatment of antithrombotic diseases. In this study, we provide a high quality genome of W. pigra and based on which, we performed a systematic identification of the potential antithrombotic genes and their corresponding proteins. We identified twenty antithrombotic gene families including thirteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. Unexpectedly, a total of 79 antithrombotic genes were identified, more than a typical blood-feeding Hirudinaria manillensis, which had only 72 antithrombotic genes. In addition, combining with the RNA-seq data of W. pigra and H. manillensis, we calculated the expression levels of antithrombotic genes of the two species. Five and four gene families had significantly higher and lower expression levels in W. pigra than in H. manillensis, respectively. These results showed that the number and expression level of antithrombotic genes of a non-hematophagous leech are not always less than those of a hematophagous leech. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a non-hematophagous leech to date and will significantly enhance the investigation and utilization of leech derivatives in thrombosis therapy research and pharmaceutical applications.

An Overview of Transferosomes: A Transdermal Drug Delivery System

A lipid bilayer including phospholipids, an edge activator, and an ethanol/aqueous core makes up transferosomes, often referred to as transferosomes, which are ultra-deformable vesicles for transdermal applications. Compared to oral and needle-based methods, this approach has a number of benefits, including self-administration, non-invasiveness, significantly reduced hepatic clearance of the medication, and increased patient compliance. The primary reason for the development of various drug delivery systems was that due to the first pass metabolism, adverse and side effects, non-patient compliance and invasive procedures, the efficient therapeutic outcomes. The advantage of transferosomes is they are barely invasive without the first pass metabolism. Transferosomes also has several advantages than liposomes due to the active surfactant properties. Due to its penetration enhancer properties, it enables the drug molecule to penetrate into the skin via the stratum corneum than other formulations. So, more research works are encouraged with respect to tranferosomes in order to formulate various new drugs in this type of drug delivery system.

Investigator- and Patient-Rated Local Tolerability in Phase 3 Trials of Topical Roflumilast in Patients With Psoriasis, Seborrheic Dermatitis, and Atopic Dermatitis

Investigator- and patient-rated local tolerability in phase 3 trials of topical roflumilast in patients with psoriasis, seborrheic dermatitis, and atopic dermatitis
 
 Christopher G. Bunick1 on behalf of the authors
 
 INTRODUCTION: Formulating a topical medication that does not irritate the skin is an important factor contributing to patient treatment adherence and satisfaction. Many topical prescription products use penetration enhancers (including propylene glycol, polyethylene glycol, and ethanol) to overcome barrier properties of the skin. However, these excipients may irritate the skin causing tolerability reactions such as burning and stinging, which can reduce patient treatment adherence. Topical roflumilast is a highly potent (Kd~0.7 nM) phosphodiesterase 4 inhibitor formulated as a water-based cream or foam that does not contain penetration enhancers or fragrances. We present prospectively assessed investigator- and patient-rated local tolerability from Phase 3 trials of topical roflumilast for patients with psoriasis (DERMIS-1, DERMIS-2, ARRECTOR) seborrheic dermatitis (SD; STRATUM), and atopic dermatitis (AD; INTEGUMENT-1, INTEGUMENT-2).
 METHODS: Patients were randomized to apply topical roflumilast (DERMIS: 0.3% cream; ARRECTOR and STRATUM: 0.3% foam; INTEGUMENT: 0.15% cream) or vehicle once daily for 8 weeks (DERMIS, ARRECTOR, and STRATUM) or 4 weeks (INTEGUMENT). Investigators assessed local tolerability on an 8-point scale (0 [no evidence of irritation] to 7 [strong reaction spreading beyond application site]) in the clinic before investigational product (IP) application. Patients reported local tolerability on a 4-point scale (0 [none: no sensation] to 3 [severe: hot, tingling/stinging sensation that has caused definite discomfort]) in the clinic 10-15 minutes after IP application. Tolerability was also assessed by reviewing documented adverse events.
 RESULTS: As assessed by investigators, ≥96.5% of patients in the roflumilast-treated groups had no evidence of irritation at the application site across all trials at all timepoints. Patient-rated local tolerability was favorable and improved with treatment: across all trials, 1% of roflumilast-treated patients reported a score of 3 (severe; defined as a “hot tingling/stinging sensation that has caused definite discomfort”) after the first application (day 1) and <1% at each subsequent assessment. Rates of adverse events, including those at the application site, were low for all trials and <0.5% of roflumilast-treated patients discontinued due to adverse events at the application site across all trials.
 CONCLUSION: Roflumilast cream and foam formulations demonstrated favorable local tolerability based on investigator- and patient-rated assessments in patients with psoriasis, SD, and AD, including application to sensitive areas such as the face and intertriginous areas.
 Sponsored by Arcutis Biotherapeutics, Inc.
 ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389; ARRECTOR: NCT05028582; STRATUM: NCT04973228; INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600

Terpene-augmented novasomal gels for the sustainment of rasagiline mesylate delivery; A new approach for treating Parkinson's disease induced by rotenone in rats

Rasagiline mesylate (RSM) is a potent anti-Parkinson's Disease (PD) drug; nevertheless, it has limited oral bioavailability due to hepatic first pass metabolism. RSM is a highly hydrophilic drug hurdled by several barriers to reach the central nervous system (CNS). This study aimed to prepare RSM-loaded novasomal gels for the transdermal delivery of the drug to CNS. Novasomes were prepared by ethanol injection method using terpenes as penetration enhancers. Design Expert® software was applied to select the optimum formulation by varying the type of terpene, amount of cholesterol, besides surface active agents (SAA): free fatty acid (FFA) ratio. The desirability calculations revealed that the optimum formulation composed of cholesterol (60 mg), SAA:FFA ratio (1:1) in the presence of eugenol. Particle size, zeta potential and entrapment efficiency of the optimum formulation were 265.90 ± 2.40 nm, −33.45 ± 0.49 mV and 83.09 ± 0.42%, respectively. TEM showed spherical well-defined nanovesicles. The optimum novasomal formulation was incorporated into gel system composed of 2% HPMC and 2% CMC. In vivo study revealed the feasibility of reversing PD symptoms regarding the behavioral, biochemical and histopathological analyses in rotenone-induced Parkinsons' rat model. A marked elevation in the number of crossovers, grooming score, frequency of rearing, gripe strength, and dopamine level besides a reduction in interleukin-17 and NLRP-3 inflammasome level when compared to positive control group were detected. No histopathological alterations were detected in examined brain sections of treated rats. In conclusion, the obtained results suggest that RSM-loaded novasomal gel formulations are promising carriers for the transdermal delivery of hydrophilic drugs like RSM.

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.

Unlocking Efficiency in Radio-Frequency Heating: Eigenfrequency Analysis for Resonance Identification and Propagation Enhancement in Nigerian Tar Sands.

Nigerian bituminous tar sands are among the world's largest deposits of bitumen and heavy oil. They are estimated to contain 38-40 billion barrels of heavy oil and bitumen, spanning approximately 120 km in length and 4-6 km in breadth. With global commitments to net zero emissions and various energy transition plans, improvements in the recovery methods for heavy oil and bitumen are being sought. To address this, renewable energy electrothermal enhanced oil recovery is considered an eco-friendly alternative. In our study, we introduce a novel Reservoir-Waveguide-Debye model. This model explores the enhancement of penetration for radio-frequency electromagnetic (EM) waves, which can be generated from renewable energy sources. These waves facilitate the viscosity reduction of heavy oil and bitumen. Through a comprehensive 2D numerical simulation employing the bulk properties of bituminous tar sands, we assess the propagation of EM fields within porous media. We utilize the industrial heating radio-frequency bandwidth of 1-60 MHz to conduct frequency domain investigations. Our analysis delves into propagation modes using eigenfrequency analysis, pinpointing the EM resonance of the tar sands. Furthermore, we investigate the impact of mesh refinement on the EM eigenfrequencies of porous media at both the microscale (400 μm) and macroscale (100 m in radial distance). Our results demonstrate the occurrence of resonance phenomena at complex eigenfrequencies around 27.12 and 54.24 MHz in both the microscale and macroscale models of the bituminous sands. This breakthrough research offers promising insights into harnessing renewable energy-driven EM waves for efficient thermal recovery processes in the Nigerian bituminous tar sands, thus fostering sustainable and eco-friendly energy solutions.

Penetration enhancers strengthen tough hydrogel bioadhesion and modulate locoregional drug delivery.

The human body possesses natural barriers, such as skin and mucosa, which limit the effective delivery of therapeutics and integration of medical devices to target tissues. Various strategies have been deployed to breach these barriers mechanically, chemically, or electronically. The development of various penetration enhancers (PEs) offers a promising solution due to their ability to increase tissue permeability using readily available reagents. However, existing PE-mediated delivery methods often rely on weak gel or liquid drug formulations, which are not ideal for sustained local delivery. Hydrogel adhesives that can seamlessly interface biological tissues with controlled drug delivery could potentially resolve these issues. Here, we demonstrate that tough adhesion between drug-laden hydrogels and biological tissue (e.g. skin and tumours) can lead to effective local delivery of drugs deep into targeted tissues by leveraging the enhanced tissue penetration mediated by PEs. The drug release profile of the hydrogel adhesives can be fine-tuned by further engineering the nanocomposite hydrogel matrix to elute chemotherapeutics from 2 weeks to 2 months. Using a 3D tumour spheroid model, we demonstrated that PEs increased the cancer-killing effectiveness of doxorubicin by facilitating its delivery into tumour microtissues. Therefore, the proposed tough bioadhesion and drug delivery strategy modulated by PEs holds promise as a platform technique to develop next-generation wearable and implantable devices for cancer management and regenerative medicine.

A Comprehensive Review on the Role of Polymers in Ocular Drug Delivery.

Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/ limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery.

Enhancement of weld penetration in 2205 stainless steel by TIG welding novel variants

Enhancement of weld penetration in 2205 stainless steel by TIG welding novel variants

Advances in the transdermal delivery of antiretroviral drugs.

Antiretroviral therapy regimens are successful in stopping the advancement of human immunodeficiency virus infection to acquired immunodeficiency syndrome, and other opportunistic infections. However, they do have significant disadvantages, including long-term treatment, limited oral bioavailability, inaccessibility to organs, non-adherence by patients, and the development of medication resistance. Because of the listed drawbacks of available routes and the availability of curative medicines for human immunodeficiency virus/acquired immunodeficiency syndrome, advanced solutions are required. Antiretroviral therapy transdermal delivery is one of the current strategies that have attracted much attention from many researchers. In this narrative review, various in vitro, in vivo, and ex vivo transdermal antiretroviral therapy delivery strategies were reviewed, such as transdermal patches and films, lipid-based nano-delivery systems, microneedles, chemical penetration enhancers, and iontophoresis, which showed promising results. Although the majority of studies on Antiretroviral transdermal delivery have produced hopeful findings, additional in-depth research on passive and physical enhancement techniques, both existing and new, is necessary to fully understand the potential of this route and to make it accessible to human immunodeficiency virus patients.

Lipo-polymeric nano-complexes for dermal delivery of a model protein.

Delivering macromolecules across the skin poses challenges due to the barrier properties of stratum corneum. Different strategies have been reported to cross this barrier, such as chemical penetration enhancers and physical methods like microneedles, sonophoresis, electroporation, laser ablation, etc. Herein, we explored a cationic lipo-polymeric nanocarrier to deliver a model protein across the skin. A cationic amphiphilic lipo-polymer was used to prepare blank nanoplexes, which were subsequently complexed with anionic fluorescein-tagged bovine serum albumin (FITC-BSA). Blank nanoplexes and FITC-BSA complexed nanoplexes showed sizes of 93.72 ± 5.8 (PDI-0.250) and 145.9 ± 3.2 nm (PDI-0.258), respectively, and zeta potentials of 25.6 ± 7.0 mV and 9.17 ± 1.20 mV. In vitro cell culture, and toxicity studies showed optimal use of these nanocarriers, with hemocompatibility data indicating non-toxicity. Ex vivo skin permeation analysis showed a skin permeation rate of 33% after 24 h. The optimized formulation was loaded in a carbopol-based gel that exhibits non-Newtonian flow characteristics with shear-thinning behavior and variable thixotropy. The nanoplexes delivered via gel demonstrated skin permeation of 57% after 24 h in mice skin ex vivo. In vivo skin toxicity testing confirmed the low toxicity profile of these nanocarriers. These results are promising for the transdermal/dermal delivery of macromolecules, such as protein therapeutics, using nanoplexes.

Review on Tropical Carriers of Antifungal Drug Therapy

Among the most prevalent conditions affecting the skin are fungus infections. OTC and oral antifungal medications are used in treatment regimens. Considering the potential negative effects of oral treatment, the topical method is usually favoured. Soon, traditional products like gels, ointments, and creams may become obsolete due to advancements made in formulation. When used to treat cutaneous fungal infections, a number of carrier systems that are packed with antifungal medications have shown encouraging outcomes. These more recent carriers include liposomes, ethosomes, liposomes, Microemulsion, and lipid systems such solid lipid nanoparticles and nanostructured lipid carriers. Penetration enhancer vesicles are another example of these newer carriers. Compared to cream and ointment, gel and composition have superior stability and application qualities. Among the most prevalent dermatology issues are skin interactions resulting from fungal infections. The most effective treatment for cutaneous infections is topical medication.

Formulation and Evaluation of Biopolymer Incorporated Nanogel of Nabumetone

ABSTRACT: The objective of this research was to improve the solubilization, dissolution rate, and thereby anti-inflammatory activity of the BCS class II drug Nabumetone (NSAID). A solid dispersion (SD) approach with Gelucire 50/13 was used to enhance the solubility. Microwave-induced fusion method was used for the development of SD, as it demonstrated a remarkable increase in the solubility and dissolution rate of pure drugs when compared to traditional solid dispersions. A number of parameters of the SD were evaluated in vitro, including solubility, dissolution, and Fourier Transformed Infrared Spectra obtained (FT-IR). The rate of dissolution was inclined to betterment with the drug: polymer ratio 1:0.5 showing drug release 99.60 ± 29. The objective of the work was to evolve a Nanogel for topical delivery of Nabumetone. The emulsification-diffusion method was used to create nanogel using the polymers Carbopol-940, Gelucire-50/13, and triethanolamine as gelling agents. Chitosan was added to the formulation as a biopolymer. Menthol was employed as a penetration enhancer. Using the spontaneous emulsification-diffusion method, six distinct formulations of Nabumetone-loaded Nanogel were successfully created and evaluated for particle size, zeta potential, thermodynamic stability, and rheology study. Using a cellophane membrane, the gels were examined for diffusion study further, and drug content, viscosity, spreadability, pH, and clarity were accessed. The formulation F4 batch had the best in-vitro drug release profile, with a 96.04% release rate over 270 minutes. Optimized gel F4 underwent a skin irritation study on Wistar rats and passed the test. The topical application of Nabumetone as Nanogel proved to be an effective approach to drug delivery.