Electrospun PVA nanofiber mat for topical Deflazacort delivery: accentuated anti-inflammatory efficacy for wound healing.

PURPOSE: Asses the wound healing activity of Polyvinyl alcohol - Deflazacort (PVA-DEF) nanofibers mats synthesized by electrospinning technology. METHODS: PVA-DEF nanofiber mats were created with various PVA polymer concentrations using an electrospinning process. The morphological features and diameter of the electrospun nanofibrous mats were investigated using scanning electron microscopy (SEM). The in vitro DEF release rate from PVA electrospun nanofibrous mats was evaluated. In addition to assessing wound healing activity in vivo, histological, and immunochemical tests were conducted. RESULTS: Results revealed a uniform and smooth surface of the fiber with an average diameter of the selected fibers of 533.9 nm ± 45.83. Also, PVA electrospun nanofiber mats showed an initial burst release of more than 50% of the DEF in 1 h, and the rest of the DEF was released gradually for up to 480 min. Fickian diffusion is the main DEF release mechanism from PVA electrospun nanofiber mats. In male Wistar albino rats with 1 cm2 excision wounds, in vivo studies revealed a significant improvement in wound healing rate via modulation of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) expression. CONCLUSION: PVA-DEF nanofiber mats can be used effectively for improving wound healing.

Effect of PEGylation on the Drug Release Performance and Hemocompatibility of Photoresponsive Drug-Loading Platform.

Coronary stenosis has been one of the most common heart diseases that drastically increases the risk of fatal disorders such as heart attack. Angioplasty using drug coated balloons (DCB) has been one of the most safe and promising treatments. To minimize the risk of thrombosis of such DCBs during intervention, a different approach that can secure high hemocompatibility under blood flow is necessary. Here we report a method of improving the photoresponsive platform's hemocompatibility by conjugating polyethylene glycol (PEG), onto the functional groups located at the balloon surface. In this study, latex microbeads were used as models for balloons to enable precise observation of its surface under microscopy. These beads were decorated with PEG polymers of a variety of lengths and grafting densities, along with the Cy5-Photoclevable (PC) linker conjugate to mimic drugs to be loaded onto the platform. Results showed that PEG length and grafting density are both critical factors that alter not only its hemocompatibility, but also the drug load and release efficiency of such platform. Thus, although further investigation is necessary to optimize the tradeoff between hemocompatibility, drug load, and release efficiency, it is safe to conclude that PEGylation of DCB surface is an effective method of enhancing and maintaining high hemocompatibility to minimize the risk of thrombosis during angioplasty.

Mechanisms of Penetration Enhancement and Transport Utilizing Skin Keratine Liposomes for the Topical Delivery of Licochalcone A.

Keratin liposomes have emerged as a useful topical drug delivery system given theirenhanced ability to penetrate the skin, making them ideal as topical drug vehicles. However, the mechanisms of the drug penetration enhancement of keratin liposomes have not been clearly elucidated. Therefore, licochalcone A(LA)-loaded skin keratin liposomes (LALs) were prepared to investigate their mechanisms of penetration enhancement on the skin and inB16F10 cells. Skin deposition studies, differential scanning calorimetry (DSC), attenuated total reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and skin distribution and intracellular distribution studies were carried out to demonstrate the drug enhancement mechanisms of LALs. We found that the optimal application of LALs enhanced drug permeation via alterations in the components, structure, and thermodynamic properties of the stratum corneum (SC), that is, by enhancing the lipid fluidization, altering the skin keratin, and changing the thermodynamic properties of the SC. Moreover, hair follicles were the main penetration pathways for the LA delivery, which occurred in a time-dependent manner. In the B16F10 cells, the skin keratin liposomes effectively delivered LA into the cytoplasm without cytotoxicity. Thus, LAL nanoparticles are promising topical drug delivery systems for pharmaceutical and cosmetic applications.

Metronidazole-loaded nanostructured lipid carriers to improve skin deposition and retention in the treatment of rosacea.

The objective of the present investigation was to improve the skin deposition and retention of metronidazole (MTZ) in rosacea therapy by incorporating it into nanostructured lipid carriers (NLCs). The main challenge in this endeavor was the partial hydrophilicity of MTZ, which mandated careful selection of excipients, including solid and liquid lipids, surfactants, and their ratios in combination. NLCs were produced by the phase inversion temperature method and finally converted into a gel for topical application. The prepared nanoparticles were evaluated for their particle size, zeta potential, entrapment efficiency, solid-state characteristics, surface morphology, in vitro drug release, and permeation through excised skin. The gel was additionally characterized for its pH, drug content, viscosity, and spreadability. The prepared nanoparticles were spherical in shape and of size less than 300 nm. Incorporation of judiciously chosen excipients made possible a relatively high entrapment efficiency of almost 40%. The drug release was found to be biphasic, with an initial burst release followed by sustained release up to 8 hours. In comparison to the plain drug gel, which had a tissue deposition of 11.23%, the NLC gel showed a much superior and desirable deposition of 26.41%. The lipophilic nature of the carrier, its size, and property of occlusion enabled greater amounts of drug to enter and be retained in the skin, simultaneously minimizing permeation through the skin, i.e. systemic exposure. The results of the study suggest that NLCs of anti-rosacea drugs have the potential to be used in the therapy of rosacea.

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

Polyacrylic acid polymers hydrogels intended to topical drug delivery: preparation and characterization.

CONTEXT: Bioadhesiviness of polyacrylic acid polymers make them promising hydrogels to design topical drug delivery systems, allowing a close contact with biological substrate as well as an enhanced local concentration gradient, both factors that may improve the biological performance of the drugs. AIM: Texture and bioadhesive properties of hydrogels were assessed by using texture analyzer and they were correlated with their rheological behavior and performance as drug delivery systems. METHODS: Aqueous dispersions of both polymers were prepared at 0.5%, 1.0% and 1.5% w/v. Hardness, compressibility, adhesiveness, cohesiveness, bioadhesion, continuous flow, oscillatory dynamic test and in vitro drug release were evaluated. RESULTS: Rheological and texture parameters were dependent on polymer concentration and C974P polymer built the strongest structures. Both 1.5% hydrogels presented high bioadhesion values. About 50% of the metronidazole (MTZ) was sustained released from hydrogels within 2 h with an initial burst release at early stage. After, the release rates were decreased and 10% of the MTZ was released in the next 10 h. The drug release process was driven by Fickian diffusion and complex mechanism for PP and C974P hydrogels, respectively. CONCLUSION: The set of results demonstrated that these hydrogels are promising to be used as topical controlled drug delivery system.

Potential strategy of microneedle-based transdermal drug delivery system for effective management of skin-related immune disorders.

Skin-related immune disorders are a category of diseases that lead to the dysregulation of the body's immune response due to imbalanced immune regulation. These disorders exhibit diverse clinical manifestations and complicated pathogenesis. The long-term use of corticosteroids, anti-inflammatory drugs, and immunosuppressants as traditional treatment methods for skin-related immune disorders frequently leads to adverse reactions in patients. In addition, the effect of external preparations is not ideal in some cases due to the compacted barrier function of the stratum corneum (SC). Microneedles (MNs) are novel transdermal drug delivery systems that have theapparent advantages ofpenetrating the skin barrier, such as long-term and controlled drug delivery, less systemic exposure, and painless and minimally invasive targeted delivery. These advantages make it a good candidate formulation for the treatment of skin-related immune disorders and a hotspot for research in this field. This paper updates the classification, preparation, evaluation strategies, materials, and related applications of five types of MNs. Specific information, including the mechanical properties, dimensions, stability, and in vitro and in vivo evaluations of MNs in the treatment of skin-related immune disorders, is also discussed. This review provides an overview of the advances and applications of MNs in the effective treatment of skin-related immune disorders and their emerging trends.

Polymeric Nanohydrogel in Topical Drug Delivery System.

Nanohydrogels (NH) are biodegradable polymers that have been extensively studied and utilized for various biomedical applications. Drugs in a topical medication are absorbed via the skin and carried to the intended location, where they are metabolized and eliminated from the body. With a focus on their pertinent contemporary treatments, this review aims to give a complete overview of recent advances in the creation and application of polymer NH in biomedicine. We will explore the key features that have driven advances in nanotechnology and discuss the significance of nanohydrogel-based formulations as vehicles for delivering therapeutic agents topically. The review will also cover the latest findings and references from the literature to support the advancements in nanotechnological technology related to the preparation and application of NH. In addition, we will also discuss the unique properties and potential applications of NH as drug delivery systems (DDS) for skin applications, underscoring their potential for effective topical therapeutic delivery. The challenge lies in efficiently delivering drugs through the skin's barrier to specific areas with high control. Environmentally sensitive systems, like polymer-based NH, show promise in treating dermatological conditions. Polymers are pivotal in developing these drug delivery systems, with NH offering advantages such as versatile drug loading, controlled release, and enhanced skin penetration.

An Outlook Towards Nano-Sponges: A Unique Drug Delivery System and its Application in Drug Delivery.

Nanosponges are colloidal and crosslinked nanocarriers consisting of a solid mesh-like network with nanocavities to encompass various types of substances like antineoplastic, proteins, peptides, volatile oil, DNA and then incorporated into topical medications that are mainly formulated such as gels, creams, lotions, ointments, liquid and powders etc. for topical drug delivery system. In the polymeric construction of nanosponges, the release of enthalpy-rich water molecules accounts for high complexation efficiency for different molecular substances. The benefits of nanosponges involve the extended and controlled release of encapsulated particles with excellent competence and great stability. Nanosponges assume a significant part in new varieties of medicaments, beautifiers, farming, horticulture, high atomic weight containing proteins, innovative fire retardants, gas transporters, and water filters. Nanosponges are a novel technology that offers controlled and targeted drug delivery by various routes like oral, parenteral, and topical routes. Nanosponges are an effective transporter for biologically active ingredients; therefore, it is broadly employed in anti-cancer, antiviral, antiplatelet, and antilipidemic therapy. This review article gives attention to the general introduction, merits and demerits, classification, characteristic features, procedures for developing nanosponges, and numerous factors which affect nanosponge formulation, evaluation parameters, and applications in the medicinal industry.

Topical systems for the controlled release of antineoplastic Drugs: Oxidized Alginate-Gelatin Hydrogel/Unilamellar vesicles.

The efficacy of chemotherapeutic procedures relies on delivering proper concentrations of anti-cancer drugs in the tumor surroundings, so as to prevent potential side effects on healthy tissues. Novel drug carrier platforms should not just be able to deliver anticancer molecules, but also allow for adjustements in the way these drugs are administered to the patients. We developed a system for delivering water-insoluble drugs, based on the use of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), or bis(2-ethylhexyl) sulfosuccinate benzyl-n-hexadecyldimethylammonium (BHD-AOT), embedded into oxidized alginate-gelatin (ADA/Gel) hydrogel, emulating a patch for topic applications. After being loaded with curcumin, cancer cells such as human colorectal adenocarcinoma (HCT116 and DLD-1) and melanoma cell lines (MEL501), and non-malignant cells such as mammary epithelial cell lines (NMuMG) and embryonal fibroblasts (NIH 3T3 or NEO cells) were analyzed for biocompatibility and cytotoxic effects. The results show that the proposed system can load comparatively higher concentrations of the drug (with respect to other nano/microcarriers in the literature), and that it can enhance the likelihood of the drug being uptaken by cancer cells instead of non-malignant cells. These assays were complemented by diffusion studies across the stratum corneum of rat skin, with the aim of determining the system's efficiency during topical application. Finally, the stability of the patch was tested after lyophilization to determine its potential pharmaceutical use. As a whole, the combined system represents a highly reliable and robust method for embedding and delivering complex insoluble chemotherapeutical molecules, and it is less invasive than other alternative methods in the literature.

Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of inflammatory pain, such as in osteoarthritis. Ketorolac tromethamine is considered to be an NSAID with strong anti-inflammatory and analgesic potency, however, traditional applications, such as oral administration and injections, often induce high systemic exposure, leading to adverse events such as gastric ulceration and bleeding. To address this key limitation, herein we designed and fabricated a topical delivery system for ketorolac tromethamine via cataplasm, which is based on a three-dimensional mesh structure formed by the cross-linking of dihydroxyaluminum aminoacetate (DAAA) and sodium polyacrylate. The viscoelasticity of the cataplasm was characterized by rheological methods and exhibited a "gel-like" elastic property. The release behavior showed a Higuchi model characteristic with a dose dependence. To enhance the skin permeation, permeation enhancers were added and screened utilizing ex vivo pig skin, in which 1,2-propanediol was found to have the optimal permeation-promoting effect. The cataplasm was further applied to a rat carrageenan-induced inflammatory pain model, which showed comparable anti-inflammatory and analgesic effects with oral administration. Finally, the biosafety of the cataplasm was tested in healthy human volunteers, and reduced side effects were achieved as compared to the tablet formulation, which can be ascribed to less systemic drug exposure and lower blood drug concentrations. Therefore, the constructed cataplasm can reduce the risk of adverse events while maintaining efficacy, thus serving as a better alternative for the treatment of inflammatory pain, including osteoarthritis.

Natural medicine combined with nanobased topical delivery systems: a new strategy to treat psoriasis.

Psoriasis, an autoimmune inflammatory skin disorder, is one of the commonest immune-mediated disease conditions affecting individuals globally. At the moment, the conventional methods applied against psoriasis treatment have various drawbacks involving limited efficacy, skin irritation, immunosuppression, etc. Therefore, it is important for scientists to find a more potent and alternative drug approach towards psoriasis therapeutics. Natural medicine still remains an important source for new drug discovery due to its therapeutical significance in various drug administration routes. However, the traditional formulation of topical therapies for psoriasis is limited in efficacy, which limits the use of natural medicine. Based on the aforementioned limitations, the use of nanocarriers in preparation of these topical herbal products could be tremendously beneficial in enhancing the efficacy of topical medications. Growing pieces of evidence have proposed that the utilization of nanocarriers in transdermal preparation as a prospective technique, with regards to better potency, directs drug absorption to site of action, and minimum toxicity effect respectively. In the course of this review, we emphasized the pathological mechanism of psoriasis, natural medicine formula, active components of natural medicine, and nanopreparations used in the treatment of psoriasis.

Nanostructured lipid carrier-embedded polyacrylic acid transdermal patches for improved transdermal delivery of capsaicin.

Capsaicin has been used as a topical treatment for skeletomuscular and neuropathic pain. However, it has some side effects when it is applied to the skin such as burning, erythema, and skin irritation resulting in poor patient compliance. These adverse effects are caused by the rapid penetration of capsaicin into the outer layer of the epidermis and low permeation to the dermis layer. This study aimed to develop nanostructured lipid carriers (NLCs) embedded transdermal patches for improved transdermal delivery of capsaicin. An optimum formulation of NLCs (0.3% capsaicin) with a particulate size smaller than 200 nm, narrow size distribution, and acceptable colloidal stability was used for preparing transdermal patches. Polyacrylic acid (7%) was employed as the polymer base of the transdermal patches as it provided high adhesive performance and a sustained release of capsaicin. Moreover, the patches containing capsaicin-loaded NLCs could offer a higher deposition of capsaicin in the deeper layer of the skin compared to the conventional capsaicin patches. In vivo skin irritation studies indicated that the conventional capsaicin patches can cause skin irritation and redness, whereas capsaicin NLCs-loaded patches exhibited lower skin side effects. Therefore, the capsaicin NLCs-loaded patches could be a potential delivery system of capsaicin through the skin with possibly reduced skin irritation.

Mechanism insight on drug skin delivery from polyurethane hydrogels: Roles of molecular mobility and intermolecular interaction.

Though polyurethane (PU) hydrogel had great potential in topical drug delivery system, drug skin delivery behavior from hydrogel and the underlying molecular mechanism were still unclear. In this study, PU and Carbomer (CP as control) hydrogels were prepared with lidocaine (LID) and ofloxacin (OFX) as model drugs. In vitro skin permeation and tissue distribution study were conducted to evaluate the drug delivery behaviors. The underlying molecular mechanisms were characterized by drug release with octanol as release medium, rheological study, ATR-FTIR, NMR, and molecular simulation. The results showed that the skin permeation amount of LID-PU (45.50 ± 7.12 µg) was lower than LID-CP (45.50 ± 7.12 µg). And the LID diffusion coefficient of PU (26.21 µg/h0.5) was also lower than CP (31.30 µg/h0.5), which attributed to H-bonding between LID (-CONH) and PU (-NHCOO). However, the OFX-PU showed a higher skin permeation amount (10.06 ± 1.29 µg) than OFX-CP (5.28 ± 1.39 µg). And the OFX-PU also showed a higher diffusion coefficient (30.0 µg/h0.5) than OFX-CP (21.37 µg/h0.5), which was caused by increased mobility of hydrogel when interaction action site was C-O-C in PU. In conclusion, drug skin delivery behavior from PU hydrogel was controlled by molecular mobility and intermolecular interaction, which clarified the influence of the functional group of PU hydrogel on drug skin delivery behavior and broadened our understanding of PU hydrogel application in topical drug delivery system.

Curcumin-loaded lipid-hybridized cellulose nanofiber film ameliorates imiquimod-induced psoriasis-like dermatitis in mice.

Cellulose nanofiber (CNF) is an attractive biomaterial given its film-forming properties, excellent mechanical properties and biocompatibility. Herein, CNF film was prepared as a topical drug delivery system by hybridizing curcumin (Cur)-loaded nanostructured lipid carriers (NLCs). NLCs with a mean diameter of ≈500 nm were fabricated by using a solvent diffusion method. The lipid composition of the NLCs was optimized based on the efficiency of Cur delivery to the artificial skin and mechanical strength of the developed films, where a composition containing shea butter and Capmul MCM EP exhibited the highest values of 233.2 ±â€¯96.6 µg/cm2/mg and 4.86 ±â€¯0.14 MPa, respectively. The Cur-loaded lipid-hybridized CNF (lipid@CNF) films with a smooth rather than particle-embedded surface were obtained by vacuum filtration of the NLCs and CNF mixture, which were confirmed by TEM, SEM, AFM, XPS, and FTIR analyses. The Cur-loaded lipid@CNF films exhibited more than 2.0-fold increases in Cur deposition to the epidermis of imiquimod (IMQ)-induced psoriatic mouse compared with the films without lipids, which potentially resulted from the amorphous state of Cur observed in the DSC and PXRD analyses and the permeation-enhancing effect of lipids. The in vivo anti-psoriatic efficacy test revealed that the Cur-loaded lipid@CNF films ameliorated the psoriatic skin symptoms in IMQ-induced mice, reducing the pro-inflammatory cytokine levels in the skin almost comparable to a commercially available topical corticosteroid cream. These results could be attributed to the enhanced Cur deposition along with the skin hydration effect of the films. These findings suggest that the developed CNF films can be used as a promising topical drug delivery system for psoriasis therapy.

Importance of Propellants and Excipients in Pharmaceutical Topical Aerosol.

Skin is the most suitable and recommendable organ of the human body for topical administration and the main route for topical drug delivery system. Drug delivery system is the methodology used to ensure the entry of drugs into the body, reaching their target for pharmacological action. Patients tend to prefer the painless route for drug administration. So, pharmaceutical aerosols came to existence to meet patient compliance. Many variations in excipients with respect to compatibility to drugs, stability and economy are being used to improve the aerosol system of drug delivery. The present review deals with the excipients and constituents used in a pharmaceutical aerosol system as per target delivery. SUMMARY: The review deals with the excipients and constituents used in a pharmaceutical aerosol system as per target delivery. CONCLUSION: Presently, aerosol drug delivery system has become beneficial as far as faster pharmacological action and economy are concerned. Other than the active pharmaceutical ingredient (API), the pharmacological action of the aerosol system is also dependent on the excipients used as they help the API to penetrate through the skin as fast as possible.