Search Results (82)

This review explores the enhanced transdermal therapy of several skin disorders with the application of carriers comprising phospholipid vesicular gel systems. Topical drug delivery has several advantages compared to other administration methods, including enhanced patient compliance, the avoidance of the first-pass impact associated with oral administration, and the elimination of the need for repeated doses. Nonetheless, the skin barrier obstructs the penetration of drugs, hence affecting its therapeutic efficacy. Carriers with phospholipid soft vesicles comprise a novel strategy used to augment drug delivery into the skin and boost therapeutic efficacy. These vesicles encompass chemicals that possess the ability to fluidize phospholipid bilayers, producing a pliable vesicle that facilitates penetration into the deeper layers of the skin. Phospholipid-based vesicular carriers have been extensively studied for improved drug delivery through dermal and transdermal pathways. Traditional liposomes are limited to the stratum corneum of the skin and do not penetrate the deeper layers. Ethosomes, glycerosomes, and glycethosomes are nanovesicular systems composed of ethanol, glycerol, or a combination of ethanol and glycerol, respectively. Their composition produce pliable vesicles by fluidizing the phospholipid bilayers, facilitating deeper penetration into the skin. This article examines the impact of ethanol and glycerol on phospholipid vesicles, and outlines their respective manufacturing techniques. Thus far, these discrepancies have not been analyzed comparatively. The review details several active compounds integrated into these nanovesicular gel systems and examined through in vitro, in vivo, or clinical human trials involving compositions with various active molecules for the treatment of various dermatological conditions. Full article

Microneedles (MNs) have emerged as a promising tool for pain-free drug delivery, offering an alternative to traditional syringe-based methods. Among various types of MNs, dissolving microneedles fabricated from hyaluronic acid (HA) have gained attention due to their biocompatibility and ability to deliver drugs with minimal discomfort. However, conventional HA MN fabrication techniques often limit needle lengths to a few hundred micrometers, which is insufficient for deeper drug penetration. This study introduces a novel fabrication method using bidirectional drawing lithography to extend the length of HA-based MNs. By adjusting the viscosity of HA solutions and employing a controlled pulling process, we demonstrate the feasibility of producing MNs with lengths ranging from millimeters to micrometers. An average height of 15 mm and tip diameters of approximately 80 μm were successfully produced. This advancement enhances the potential of HA MNs for transdermal drug delivery and interstitial fluid sampling. Full article

Background/Objectives: The ineffective delivery of drugs into tumors and the existence of multidrug resistance (MDR) are the primary causes of chemotherapy failure. Downregulation of the Sonic Hedgehog (Shh) pathway has been shown to reduce P-glycoprotein (P-gp) expression on cell membranes and to resist MDR. Methods: In this study, we combine cyclopamine (CYP, a potent Shh antagonist) with paclitaxel (PTX, an antitumor drug that can produce MDR) in a nano-drug delivery system (CYP NP and PTX NP) for the treatment of drug-resistant breast cancer. Nanoparticles were characterized for size, zeta potential, and encapsulation efficiency. P-gp expression, nanoparticle accumulation, cytotoxicity, and apoptosis were evaluated in MCF-7 and MCF-7/Adr cells. Penetration ability was assessed using 3D multicellular tumor spheroids. Antitumor efficacy and nanoparticle biodistribution were validated in MCF-7/Adr-bearing nude mice models. Results: Our engineered CYP nanoparticles (~200 nm) demonstrated prolonged intratumoral retention, enabling sustained Shh pathway inhibition and P-gp functional suppression. This size-optimized formulation created a favorable tumor microenvironment for the smaller PTX nanoparticles (~30 nm), facilitating deeper tumor penetration and enhanced cellular uptake. Meanwhile, by down-regulating P-gp expression, CYP NPs could convert drug-resistant cells to PTX-sensitive cells in both cytotoxicity and apoptosis induction through the Shh pathway. The combination of CYP NP and PTX NP augmented the antitumor effects in MCF-7/Adr-bearing nude mice models. Conclusions: The CYP NP and PTX NP combination offers a new therapeutic strategy in cancer treatment. Full article

Psoriasis is a chronic and recurrent inflammatory disease driven not only by intrinsic factors such as immune system dysregulation but also by external factors, including bacterial infections. In contrast to the control of a single pathogenic pathway, combination therapies addressing both the immune and infectious components of psoriasis pathogenesis may offer a more effective strategy for controlling its progression. In this study, we developed a sprayable hydrogel incorporating tea polyphenol-loaded lauric acid liposomes (TP@LA-Lipo gel) to investigate its anti-inflammatory and antibacterial role in psoriasis. Our results demonstrated that TP@LA-Lipo modulated macrophage activity, reduced the expression of iNOS and TNF-α, and remodeled the immune microenvironment. Meanwhile, TP@LA-Lipo effectively eliminated Staphylococcus aureus and Escherichia coli through membrane disruption, mitigating the provoked inflammatory response. More importantly, TP@LA-Lipo gel, when sprayed onto the psoriasis lesions, provided sustained drug release over three days, enabling deeper penetration through the thickened stratum corneum to reach the inflamed layers beneath. Furthermore, in an imiquimod-induced psoriasis mouse model, TP@LA-Lipo gel effectively restored the damaged skin, alleviated histopathological changes, and reduced the systemic immune response. In summary, these findings indicate that TP@LA-Lipo gel offers a comprehensive strategy for effective disease management and improving the quality of life for psoriasis patients. Full article

Fungal infections pose a significant global health problem, affecting 20–25% of the population and contributing to over 3.75 million deaths annually. Clotrimazole (CLO) is a widely used topical antifungal drug, but its efficacy is limited by poor penetration through the stratum corneum. Microneedle (MN) systems, composed of micron-scale structures arranged on a patch, offer a promising strategy to overcome the outermost skin barrier and enhance drug penetration into deeper layers. However, optimizing MN design, particularly in terms of size, shape, and fabrication technology, is essential for efficient drug delivery. This study aimed to develop CLO-coated MN systems using an Liquid Crystal Display (LCD)-based 3D printing technique and a thin-film dip-coating method. A comprehensive optimization of printing parameters, including anti-aliasing, layer thickness, curing time, and printing angle, was conducted to ensure the desired mechanical properties. The optimized MNs were coated with either suspension or ethanol-based CLO-hydrogels, with ethanol hydrogel demonstrating superior characteristics. Additionally, the study investigated how microneedle geometry and coating formulation influenced drug release. Antifungal activity against reference and clinical origin Candida albicans strains varied significantly depending on the coating formulation. Finally, the acute toxicity test confirmed no significant toxic effects on Aliivibrio fischeri, indicating the potential biocompatibility and safety of the developed MN-based drug delivery system. Full article

Photodynamic therapy (PDT) is an innovative treatment that has recently been approved for clinical use and holds promise for cancer patients. It offers several benefits, such as low systemic toxicity, minimal invasiveness, and the ability to stimulate antitumor immune responses. For certain types of cancer, it has shown positive results with few side effects. However, PDT still faces some challenges, including limited light penetration into deeper tumor tissues, uneven distribution of the photosensitizer (PS) that can also affect healthy cells, and the difficulties posed by the hypoxic tumor microenvironment (TME). In hypoxic conditions, PDT’s effectiveness is reduced due to insufficient production of reactive oxygen species, which limits tumor destruction and can lead to relapse. This review highlights recent advances in photosensitizers and nanotechnologies that are being developed to improve PDT. It focuses on multifunctional nanoplatforms and nanoshuttles that have shown promise in preclinical studies, especially for treating solid tumors. One of the key areas of focus is the development of PSs that specifically target mitochondria to treat deep-seated malignant tumors. New mitochondria-targeting nano-PSs are designed with better water solubility and extended wavelength ranges, allowing them to target tumors more effectively, even in challenging, hypoxic environments. These advancements in PDT are opening new doors for cancer treatment, especially when combined with other therapeutic strategies. Moving forward, research should focus on optimizing PDT, creating more efficient drug delivery systems, and developing smarter PDT platforms. Ultimately, these efforts aim to make PDT a first-choice treatment option for cancer patients. Full article

Background/Objectives: The topical delivery of antibiotics through transethosomes shows promise for enhancing its dermal delivery for the treatment of skin infections. This study aimed to develop and characterize azithromycin-loaded transethosomes to enhance topical drug delivery and improve the antibacterial activity of azithromycin. Methods: The prepared azithromycin formulations underwent assessment for various characteristics, including their vesicle dimensions, size distribution, zeta potential, encapsulation efficiency, and morphological features (via TEM analysis). Additionally, their thermal properties were examined through DSC analysis, and their stability was monitored over six months under refrigerated storage conditions. The sequential tape-stripping technique was employed to conduct ex vivo penetration studies on human skin. Interactions between transethosomes and stratum corneum lipids were examined using attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). Additionally, the formulations were tested for their in vitro antibacterial efficacy against Staphylococcus aureus. Results: The findings revealed that AZ 1 and AZ 2 had vesicle sizes of 108.44 ± 5.72 nm and 70.42 ± 6.02 nm, zeta potential measurements of −11.897 ± 1.820 mV and −34.575 ± 4.535 mV, and high entrapment efficiencies of 99.259 ± 0.086% and 99.560 ± 0.014%, respectively. Transmission electron microscopy (TEM) analysis confirmed the spherical nature of the vesicles, whereas differential scanning calorimetry (DSC) confirmed the successful encapsulation of azithromycin in transethosomes. The formulations exhibited acceptable physical stability at 4 °C for six months. Ex vivo studies revealed a significantly higher deposition of azithromycin in the skin by both transethosome formulations than by the drug solution (p < 0.05), with low systemic absorption. Among the formulations, AZ 2 resulted in much deeper skin penetration, with deeper dermal and epidermal layer deposition (1.388 ± 0.242 µg/cm²) compared to AZ 1 (four-fold higher, p < 0.05) and to the control drug solution (12 times more, p < 0.05). Analysis using ATR-FTIR suggested that azithromycin-loaded transethosomes improve the drug penetration by increasing the lipid fluidity and extracting lipids from the stratum corneum. Moreover, the transethosomes loaded with azithromycin demonstrated enhanced antibacterial efficacy against Staphylococcus aureus, with minimum inhibitory concentration (MIC) values that were lower than those of the free drug solution. Conclusion: The results highlight the promising potential of transethosomes as a novel topical drug delivery system for azithromycin that offers improved therapeutic effects against skin infections Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article

Obesity has become a major public health threat, as it can cause various complications such as diabetes, cardiovascular disease, sleep apnea, cancer, and osteoarthritis. The primary anti-obesity therapies include dietary control, physical exercise, surgical interventions, and drug therapy; however, these treatments often have poor therapeutic efficacy, significant side effects, and unavoidable weight rebound. As a revolutionized transdermal drug delivery system, microneedles (MNs) have been increasingly used to deliver anti-obesity therapeutics to subcutaneous adipose tissue or targeted absorption sites, significantly enhancing anti-obese effects. Nevertheless, there is still a lack of a review to comprehensively summarize the latest progress of MN-mediated treatment of obesity. This review provides an overview of the application of MN technology in obesity, focusing on the delivery of various therapeutics to promote the browning of white adipose tissue (WAT), suppress adipogenesis, and improve metabolic function. In addition, this review presents detailed examples of the integration of MN technology with iontophoresis (INT) or photothermal therapy (PTT) to promote drug penetration into deeper dermis and exert synergistic anti-obese effects. Furthermore, the challenges and prospects of MN technology used for obesity treatment are also discussed, which helps to guide the design and optimization of MNs. Overall, this review provides insight into the development and clinical translation of MN technology for the treatment of obesity. Full article

Skin disorders are the fourth most common cause of all diseases, which affect nearly one-third of the world’s population. Topical drug delivery can be effective in treating a range of skin disorders, including microbial infections, skin cancer, dermatitis, burn injury, wounds, and psoriasis. Bioadhesive nanoparticles (BNPs) can serve as an efficient topical drug delivery system as they can serve dual purposes as bioadhesives and nanocarriers, which can mediate targeted drug delivery, prolong retention time, and deepen drug penetration through skin layers. There is an increasing demand for BNP-based applications in medicine because of their various advantages, including biodegradability, flexibility, biocompatibility, and enhanced adhesive strength. A number of BNPs have already been developed and evaluated as potential topical drug delivery systems. In addition, a range of studies have already been carried out to evaluate the potential of BNPs in the treatment of various skin disorders, including atopic dermatitis, irritant contact dermatitis, skin cancer, psoriasis, microbial infections, wounds, and severe burn injuries. This review article is timely and unique, because it provides an extensive and unique summary of the recent advances of BNPs in the treatment of wide-ranging skin disorders. Moreover, this review also provides a useful discussion on the bioadhesion mechanism and various biopolymers that can be used to prepare BNPs. Full article

Glioblastoma (GBM) is the most aggressive brain tumor, characterized by high recurrence rates and poor patient outcomes. Treatment failure is driven by multiple factors, including complex tumor heterogeneity, the presence of cancer stem cells, the immunosuppressive tumor microenvironment (TME), and many others. GBM’s heterogeneity underlines its ability to resist therapies and adapt to the TME. The TME, which is highly immunosuppressive and shaped by hypoxia, impairs anti-tumor immunity and limits the efficacy of immunotherapy. The blood–brain barrier (BBB) remains a major obstacle to delivering sufficient drug concentrations to the tumor by restricting the penetration of therapeutic agents. Another problem is the lack of reliable biomarkers to perform better patient stratification or even guide personalized treatments, resulting in generalized therapeutic approaches that do not adequately address GBM complexities. This review highlights the multifactorial nature of GBM treatment failure and highlights the need for a paradigm shift and innovative, personalized strategies. A deeper understanding of tumor biology and advances in translational research will be crucial to developing effective therapies and improving patient outcomes in this devastating disease. Full article

Background/Objectives: This study aimed to evaluate the safety and efficacy of chitosan-based bioadhesive films for facilitating the topical delivery of curcumin in skin cancer treatment, addressing the pharmacokinetic limitations associated with oral administration. Methods: The films, which incorporated curcumin, were formulated using varying proportions of chitosan, polyvinyl alcohol, Poloxamer^® 407, and propylene glycol. These films were assessed for stability, drug release, in vitro skin permeation, cell viability (with and without radiotherapy), and skin irritation. Results: The films demonstrated physical stability and preserved curcumin content at room temperature for 90 days. Drug release was effectively controlled during the first 8 h, with release rates ranging from 51.6 ± 4.8% to 65.6 ± 13.0%. The films also enhanced drug penetration into the skin compared to a curcumin solution used as a control (stratum corneum: 1.3 ± 0.1 to 1.9 ± 0.8 µg/cm²; deeper skin layers: 1.7 ± 0.1 to 2.7 ± 0.2 µg/cm²). A cytotoxicity test on metastatic melanoma cells showed that curcumin at topical doses exerted activity similar to that delivered via the skin. Furthermore, curcumin alone was more effective in inhibiting tumor cells than radiotherapy alone (p < 0.01), with no additional benefit observed when curcumin was combined with radiotherapy. Finally, irritation tests confirmed that the films were safe for topical application. Conclusion: The developed chitosan-based bioadhesive films represent a promising alternative for the topical treatment of skin tumors using curcumin. Full article

One of the major challenges in dermal drug delivery is the adequate penetration of the active compound into the skin without causing any skin irritation and inflammation. Nanocrystals (NCs) are nanoscale particles, and their sizes are below 1000 nm. NCs are made up of drug particles only, which are used to improve the aqueous solubility and bioavailability of poorly water-soluble drugs. NCs are typically prepared either by bottom-up or top-down techniques. The advantages of using NC-based formulations in enhancing dermal drug delivery include increased drug loading capacity, easier and deeper penetration into the skin tissue, and increased passive diffusion. NC-based formulations with the capacity of enhanced dermal drug delivery can be effectively used to treat a wide range of skin disorders, including melanoma, inflammation, psoriasis, acne vulgaris, bacterial infections, fungal infections, eczema, skin aging, herpes simplex virus infections, skin manifestations of tick bites, frostbite-related infections, hyperpigmentation, and diabetic foot ulcer. In this review, major challenges in dermal drug delivery across the skin barrier, mechanism of action of dermal NCs, advantages of using NCs in enhancing dermal drug delivery, NC preparation methods, and applications of NCs in the treatment of various skin disorders have been discussed. Full article

Essential oils (EOs) are known for their diverse bioactivities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, skin-barrier repairing and anticancer, and therefore, hold profound potential to be used in cosmetic and skincare products. Owing to these properties, EOs have long been utilized to address a range of dermatological issues, from acne and inflammation to aging and dryness. However, problems associated with EOs beset their practical applications, which include high volatility, oxidation, hydrophobic nature, low bioavailability, skin irritation, chemical transformation and poor stability in air and light. A prospective of nanolipidic formulations, including the nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) system for improved skin delivery of these EOs highlights the possibility of their use in topical applications, which offer several advantages such as improved bioavailability and stability, lower toxicity and higher drug content. These nanoformulations protect the EOs from environmental degradation and improve their penetration into deeper skin layers, leading to prolonged therapeutic benefits. The delivery of bioactive agents using a conventional topical preparation exhibits low penetration, frequent applications, poor adherence and prolonged therapy duration, whereas the novel delivery system exhibits improved stability of the drug, enhanced skin penetration, enhanced retention and better therapeutic efficacy. This review provides a comprehensive compendium of information on EOs, which are widely used in skincare, along with their nanolipidic formulations for maximized skincare uses. The mechanism of action of EOs as skin bioactive agents, challenges associated with their use, advances in nanolipidic formulations and their market value as cosmetic skincare products are also explored. Full article

Androgenetic alopecia (AGA) is caused by the impact of dihydrotestosterone (DHT) on hair follicles, leading to progressive hair loss in men and women. In this study, we developed caffeine-loaded hollow mesoporous silica nanoparticles coated with ultradeformable liposomes (ULp-Caf@HMSNs) to enhance caffeine delivery to hair follicles. Caffeine, known to inhibit DHT formation, faces challenges in skin penetration due to its hydrophilic nature. We investigated caffeine encapsulated in liposomes, hollow mesoporous silica nanoparticles (HMSNs), and ultradeformable liposome-coated HMSNs to optimize drug delivery and release. For ultradeformable liposomes (ULs), the amount of polysorbate 20 and polysorbate 80 was varied. TEM images confirmed the mesoporous shell and hollow core structure of HMSNs, with a shell thickness of 25–35 nm and a hollow space of 80–100 nm. SEM and TEM analysis showed particle sizes ranging from 140–160 nm. Thermal stability tests showed that HMSNs coated with ULs exhibited a Td₁₀ value of 325 °C and 70% residue ash, indicating good thermal stability. Caffeine release experiments indicated that the highest release occurred in caffeine-loaded HMSNs without a liposome coating. In contrast, systems incorporating ULp-Caf@HMSNs exhibited slower release rates, attributable to the dual encapsulation mechanism. Confocal laser scanning microscopy revealed that ULs-coated particles penetrated deeper into the skin than non-liposome particles. MTT assays confirmed the non-cytotoxicity of all HMSN concentrations to human follicle dermal papilla cells (HFDPCs). ULp-Caf@HMSNs promoted better cell viability than pure caffeine or caffeine-loaded HMSNs, highlighting enhanced biocompatibility without increased toxicity. Additionally, ULp-Caf@HMSNs effectively reduced ROS levels in DHT-damaged HFDPCs, suggesting they are promising alternatives to minoxidil for promoting hair follicle growth and reducing hair loss without increasing oxidative stress. This system shows promise for treating AGA. Full article