This study evaluates the use of poly(vinyl alcohol), collagen, and chitosan blends for developing a microneedle patch for the delivery of meloxicam (MEL). Results confirm successful MEL encapsulation, structural integrity, and chemical stability even after ethylene oxide sterilization. Mechanical testing indicates the patch has the required properties for effective skin penetration and drug delivery, as demonstrated by load-displacement curves showing successful penetration of pig ear surfaces at 3N of normal load. In vitro imaging confirms the microneedle patch penetrates the pig\'s ear cadaver skin effectively and uniformly, with histological evaluation revealing the sustained presence and gradual degradation of microneedles within the skin. Additionally, in vitro drug diffusion experiments utilizing ballistic gel suggest that microneedles commence dissolution almost immediately upon insertion into the gel, steadily releasing the drug over 24 h. Furthermore, the microneedle patch demonstrates ideal drug release capabilities, achieving nearly 100% release of meloxicam content from a single patch within 18 h. Finally, in vivo studies using pigs demonstrate the successful dissolution and transdermal drug delivery efficacy of biodegradable microneedle patches delivering meloxicam in a porcine model, with over 70% of microneedles undergoing dissolution after 3 days. While low detectable meloxicam concentrations were observed in the bloodstream, high levels were detected in the ear tissue, confirming the release and diffusion of the drug from microneedles. This work highlights the potential of microneedle patches for controlled drug release in veterinary applications.

Low-frequency sonophoresis has emerged as a promising minimally invasive transdermal delivery method. However, effectively inducing cavitation on the skin surface with a compact, low-frequency ultrasound transducer poses a significant challenge. This paper presents a modified design of a low-frequency ultrasound transducer capable of generating ultrasound cavitation on the skin surfaces. The transducer comprises a piezoelectric ceramic disk and a bowl-shaped acoustic resonator. A conical slit structure was incorporated into the modified transducer design to amplify vibration displacement and enhance the maximum sound pressure. The FEM-based simulation results confirmed that the maximum sound pressure at the resonance frequency of 78 kHz was increased by 1.9 times that of the previous design. Ultrasound cavitation could be experimentally observed on the gel surface. Moreover, 3 minutes of ultrasound treatment significantly improved the caffeine permeability across an artificial membrane. These results demonstrated that this transducer holds promise for enhancing drug permeation by generating ultrasound cavitation on the skin surface.

The stratum corneum, which acts as a strong barrier against external agents, presents a significant challenge to transdermal drug delivery. In this regard, microneedle (MN) patches, designed as modern systems for drug delivery via permeation through the skin with the ability to pass through the stratum corneum, are known to be convenient, painless, and effective. In fact, MN have shown significant breakthroughs in transdermal drug delivery, and among the various types, hydrogel MN (HMNs) have demonstrated desirable inherent properties. Despite advancements, issues such as limited loading capacity, uncontrolled drug release rates, and non-uniform therapeutic approaches persist. Conversely, nanomaterials (NMs) have shown significant promise in medical applications, however, their efficacy and applicability are constrained by challenges including poor stability, low bioavailability, limited payload capacity, and rapid clearance by the immune system. Incorporation of NMs within HMNs offers new prospects to address the challenges associated with HMNs and NMs. This combination can provide a promising field of research for improved and effective delivery of therapeutic agents and mitigate certain adverse effects, addressing current clinical concerns. The current review highlights the use of NMs in HMNs for various therapeutic and diagnostic applications.

Ionic liquids (ILs) represent an exciting and promising solution for advancing drug delivery platforms. Their unique properties, including broad chemical diversity, adaptable structures, and exceptional thermal stability, make them ideal candidates for overcoming challenges in transdermal drug delivery. Despite encountering obstacles such as side reactions, impurity effects, biocompatibility concerns, and stability issues, ILs offer substantial potential in enhancing drug solubility, navigating physiological barriers, and improving particle stability. To propel the use of IL-based drug delivery in pharmaceutical innovation, it is imperative to devise new strategies and solvents that can amplify drug effectiveness, facilitate drug delivery to cells at the molecular level, and ensure compatibility with the human body. This review introduces innovative methods to effectively address the challenges associated with transdermal drug delivery, presenting progressive approaches to significantly improve the efficacy of this drug delivery system.

OBJECTIVE: Microneedles (MNs) are minimally invasive transdermal drug delivery systems capable of penetrating the stratum corneum to overcome the barrier properties. The primary objective of this research was to prepare dissolving microneedle patches (DMNP) loaded with quetiapine (QTP).
METHODS: DMNP were fabricated employing the solvent casting technique, utilizing various polymer feed ratios including polyvinyl alcohol (PVA), polyvinylpyrrolidone K30 (PVP-K30), and polylactide-co-glycolide (PLGA) polymers. The loaded DMNP with QTP underwent a comprehensive characterization process encompassing assessments for compatibility, thickness, insertion potential, morphology, thermal behavior, X-ray diffraction, ex-vivo permeation, skin irritation, and histopathological changes.
RESULTS: FTIR studies confirmed the compatibility of QTP with the microneedle patch composites. The thickness of the drug-loaded DMNP ranged from 0.67 mm to 0.97 mm. These microneedles exhibited an impressive penetration depth of 480 μm, with over 80% of the needles maintaining their original shape after piercing Parafilm-M. SEM analysis of the optimized DMNP-2 revealed the formation of sharp-tipped and uniformly surfaced needles, measuring 570 μm in length. Remarkably, the microneedles did not elicit any signs of irritation upon application of the prepared DMNP. The DMNP-2 showcased an impressive cumulative ex-vivo permeation of QTP, reaching 17.82 µg/cm2/hr. Additionally, histopathological assessment of vital organs in rabbits attested to the safety profile of the formulated microneedle patches.
CONCLUSIONS: In conclusion, the developed microneedle patch represents a promising strategy for enhancing the transdermal delivery of QTP. This innovative approach has the potential to increase patient compliance, offering a more efficient and patient-friendly method of administering QTP.

Transdermal administration techniques have gained popularity due to their advantages over oral and parenteral methods. Noninvasive, self-administered delivery devices improve patient compliance and control drug release. Transdermal delivery devices struggle with the skin\'s barrier function. Molecules over 500 Dalton (Da) and ionized compounds don\'t permeate through the skin. Drug encapsulation in phospholipid-based vesicular systems is the most effective skin delivery technique. Vesicular carriers include bi-layered liposomes, ultra-deformable liposomes, ethanolic liposomes, transethosomes, and invasomes. These technologies enhance skin drug permeation by increasing formula solubilization, partitioning into the skin, and fluidizing the lipid barrier. Phospholipid-based delivery systems are safe and efficient, making them a promising pharmaceutical and cosmeceutical drug delivery technique. Still, making delivery systems requires knowledge about the physicochemical properties of the drug and carrier, manufacturing and process variables, skin delivery mechanisms, technological advances, constraints, and regulatory requirements. Consequently, this review covers recent research achievements addressing the mentioned concerns.

Transdermal drug delivery (TDD) has attracted widespread attention because of the advantage of its non-invasive nature, easy self-administration, and low side effects. The key to this pathway of drug delivery is how to overcome the barrier of the lipid matrix in the stratum corneum (SC). In this work, molecular dynamics (MD) were employed to investigate the adsorption of thyrotropin-releasing hormone (TRH) on the SC, and the effects of three different chemical permeation enhancers (ethanol (ETOH), carveol (CAV), and borneol (BOR)) on the SC were analyzed. The results showed that ETOH hardly altered the order of lipids in the SC, while CAV and BOR disrupted the morphology of the SC. The primary target of CAV was the CHOL in SC, which not only disrupted the ordered arrangement of CHOL, but also \"extracted\" CHOL from SC. The thickness distribution of SC became more inhomogeneous in the presence of CAV and BOR, which facilitated the penetration of drug molecules. Compared to no chemical permeation enhancers, the free energy of permeation in the presence of chemical permeation enhancers was less than 4-10 kcal mol-1, which suggested that chemical permeation enhancers were more favorable for the permeation of drugs from viewpoints of thermodynamics. All the results provided theoretical insights into the effect of chemical permeation enhancers on the transdermal permeation of drugs.

The global demand for an enhanced quality of life and extended lifespan has driven significant advancements in tissue engineering and regenerative medicine. These fields utilize a range of interdisciplinary theories and techniques to repair structurally impaired or damaged tissues and organs, as well as restore their normal functions. Nevertheless, the clinical efficacy of medications, materials, and potent cells used at the laboratory level is always constrained by technological limitations. A novel platform known as adaptable microneedles has been developed to address the abovementioned issues. These microneedles offer a solution for the localized distribution of various cargos while minimizing invasiveness. Microneedles provide favorable patient compliance in clinical settings due to their effective administration and ability to provide a painless and convenient process. In this review article, we summarized the most recent development of microneedles, and we started by classifying various microneedle systems, advantages, and fundamental properties. Subsequently, it provides a comprehensive overview of different types of microneedles, the material used to fabricate microneedles, the fundamental properties of ideal microneedles, and their applications in tissue engineering and regenerative medicine, primarily focusing on preserving and restoring impaired tissues and organs. The limitations and perspectives have been discussed by concluding their future therapeutic applications in tissue engineering and regenerative medicines.

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

In the modern environment conscious era, there has been a huge demand for the effective green method to fabricate biomaterials for sustained transdermal release of diltiazem hydrochloride to treat hypertension and cardiac failure. In this vein, the present study explores the amination of waste jute sourced nanocellulose (ANC) and its effect as a reinforcing filler to design electrospun polyvinyl alcohol (PVA)/chitosan based polymeric nanofibrous scaffold for drug delivery. The characterization results of FTIR (Fourier Transform Infrared Spectroscopy) confirm the successful chemical modification of nanocellulose (NCC). SEM (Scanning Electron Microscopy) results indicate the morphological modifications in ANC due to grafting. ANC enhances the mechanical properties of scaffold and sustains the release of the loaded drug to 67.89±3.39% as compared to the pure PVA/chitosan scaffold of 92.63±4.63% over a period of 72 h as shown by the results of in-vitro drug release study. Moreover, the incorporation of 0.5 % ANC improves the anti-bacterial activity against both gram-positive (97.4±4.87%, reduction in viable cells count) and gram-negative bacteria (98.5±4.93%, reduction in viable cells count). Further, the skin irritation and MTT assay authenticate the biocompatibility of the developed scaffold. The overall findings hence prove the efficacy of the engineered scaffold as a potential transdermal patch for sustained drug delivery applications.