Microneedles are emerging drug delivery methods for painless treatment. The current study tested dissolving microneedles containing lidocaine (Li-DMN) for use in local anesthesia. An Li-DMN patch was fabricated by centrifugal lithography with carboxymethyl cellulose as a structural polymer and assessed for physical properties by optical microscopy and a fracture force analyzer. The biocompatibility was evaluated by a histology section in vitro and by ear thickness in vivo. The efficacy of the Li-DMN patch was assessed by electrophysiological recordings in primary cultured sensory neurons in vitro and a von Frey test on rats’ hind paws in vivo. The physical properties of the microneedle showed enough rigidity for transdermal penetration. The maximal capacity of lidocaine-HCl in the Li-DMN patch was 331.20 ± 6.30 µg. The cytotoxicity of the dissolving microneedle to neuronal cells was negligible under an effective dose of lidocaine for 18 h. Electrophysiological recordings verified the inhibitory effect of the voltage-gated sodium channel current by the Li-DMN patch in vitro. A skin reaction to the edema test and histologic analysis of the rats’ ears after application of the Li-DMN patch were negligible. Also, the application of the Li-DMN patch reduced the nocifensive behavior of the rats almost immediately. In conclusion, the dissolving microneedle patch with carboxymethyl cellulose is a promising candidate method for the painless delivery of lidocaine-HCl.

Advancements in micro‐resolution 3D printers have significantly facilitated the development of highly complex mass‐producible drug delivery platforms. Conventionally, due to the limitations of micro‐milling machineries, dissolvable microneedles (MNs) are mainly fabricated in cone‐shaped geometry with limited drug delivery accuracy. Herein, to overcome the limitations of conventional MNs, a novel projection micro‐stereolithography 3D printer‐based self‐locking MN for precise skin insertion, adhesion, and transcutaneous microdose drug delivery is presented. The geometry of self‐locking MN consists of a sharp skin‐penetrating tip, a wide skin interlocking body, and a narrow base with mechanical supports fabricated over a flexible hydrocolloid patch to improve the accuracy of skin penetration into irregular surfaces. Melanoma, a type of skin cancer, is selected as the model for the investigation of self‐locking MNs due to its irregular and uneven surface. In vivo immunotherapy efficacy is evaluated by integrating SD‐208, a novel transforming growth factor‐β (TGF‐β) inhibitor that suppresses the proliferation and metastasis of tumors, and anti‐PD‐L1 (aPD‐L1 Ab), an immune checkpoint inhibitor that induces T cell‐mediated tumor cell death, into self‐locking MNs and comparing them with intratumoral injection. Evaluation of (aPD‐L1 Ab)/SD‐208 delivery effectiveness in B16F10 melanoma‐bearing mice model confirms significantly improved dose efficacy of self‐locking MNs compared with intratumoral injection.

The dissolving microneedle (DMN) patch is a transdermal delivery system, containing arrays of micro-sized polymeric needles capable of encapsulating therapeutic drugs within their matrix and releasing them into the skin. However, the elastic properties of the skin prevent DMNs from complete insertion and accurate delivery of encapsulated compounds into the skin. Moreover, the adhesive materials used in patches may cause skin irritation, inflammation, and redness. Therefore, we developed a patchless, micro-pillar integrated DMN (P-DMN) that is simple to fabricate and enhances transdermal drug delivery compared with traditional DMN patches. The micro-pillars were made of polymethyl methacrylate at a height of 300 μm and a base diameter of 500 μm. To fabricate P-DMNs, we employed hyaluronic acid, which is a widely used derma filler and plays a role in tissue re-epithelialization. We demonstrate that utilizing P-DMNs significantly improves the delivery efficiency of an encapsulated drug surrogate (91.83% ± 7.75%) compared with traditional DMNs (64.86% ± 8.17%). Interestingly, P-DMNs remarkably increase the skin penetration accuracy rate of encapsulated drugs, up to 97.78% ± 2.22%, compared with 44.44% ± 7.85% in traditional DMNs. Our findings suggest that P-DMNs could serve as a highly accurate and efficient platform for transdermal delivery of various types of micro- and macro-biomolecules.

Dissolving microneedle (DMN) patches were developed as efficient and patient-friendly transdermal delivery systems for biopharmaceuticals. However, recent studies have confirmed that the efficiency of DMNs to deliver biopharmaceuticals is highly reduced because of incomplete insertion caused by the stiffness and elastic properties of the skin. Therefore, micropillar integrated DMNs were developed to overcome the insertion limitations of DMN patches. Although micropillars were designed as integrated applicators to implant DMNs across the skin, they can also become inserted into the skin, leading to skin injury and inflammation. Herein, we have developed a separable micropillar integrated DMN (SPDMN) capable of inserting DMNs across the skin with high efficiency while minimizing skin injury risk through the introduction of a safety ring feature. Unlike previously developed systems, the SPDMN does not require continuous skin attachment and can be detached immediately post-application, leaving DMNs implanted inside the skin. Altogether, the findings of this study lead to the development of a quick, safe, and efficient DMN-based drug delivery platform.

Alopecia, characterized by hair follicle blockage and hair loss, disrupts the normal cycle of hair growth. Although not a life-threatening condition, a growing body of evidence suggests that the psychological state of individuals experiencing alopecia can be highly influenced. Despite considerable research on hair loss treatment, interest in micro-pigmentation has increased in recent decades. Micropigmentation is an effective method to camouflage the visual contrast between the scalp and hair strands. However, the localization, intensity and dimension of microdots depend highly upon the physician performing the implantation. Incorrectly localized microdots within the skin may lead to patchy or faded micropigmentation. To overcome the limitations of conventional micro-pigmentation, we aimed to develop micro-pigment-encapsulated biodegradable microneedles (PBMs), capable of accurately implanting pigments below the epithelial-dermal junction of the scalp in a minimally invasive manner. A tissue interlocking microneedle technique was utilized to fabricate double-layered PBMs over a biodegradable flexible sheet, which could be washed off post-implantation. We confirmed that the intensity, dimension and insertion depth of 1,000 μm-long PBMs was maintained on pig cadaver skin over time. This study suggested that the developed PBMs would serve as an attractive platform for scalp micro-pigmentation in the future.

Background: Transdermal drug delivery by means of polymeric microneedles (PMNs) offers the advantage of overcoming some of the disadvantages of oral medication, such as first-pass metabolism, through painless, controlled drug release. Lawsone, isolated from Lawsonia inermis, exhibits reported antioxidant, anti-inflammatory, antimicrobial, and antitumor properties, suggesting its use as a promising candidate for topical application. Objectives: Fabrication and optimization of hyaluronic acid-carboxymethylcellulose (HA-CMC) PMNs loaded with lawsone with respect to enhancing transdermal delivery and understanding release and physicochemical characteristics. Methods: Hyaluronic acid-carboxymethylcellulose-lawsone patches were prepared by micromolding. The Box-Behnken design approach was then utilized to identify the appropriate concentrations of carboxymethylcellulose (CMC) (0.15% to 0.35% w/w), hyaluronic acid (HA) (0.01% to 0.09% w/w), and polyethylene glycol 400 (PEG 400) (0.5% to 1.5% w/w), all of which are dependent on drug release after 90 minutes. Morphological examination was conducted using light and scanning electron microscopy (SEM). The levels of transepidermal water loss (TEWL), drug content, insertion rate, mechanical properties, and release of the patches were assessed. Results: The optimized formulation showed a cumulative release of 59.63% in 90 min, following Higuchi release kinetics. Polymeric microneedles showed uniform morphology, a failure force of 0.48 N, full penetration of 375 μm, and reversible changes in TEWL. Conclusions: Hyaluronic acid-carboxymethylcellulose PMNs offer a promising formulation strategy for the transdermal delivery of lawsone. This preliminary study establishes a biocompatible platform with potential for future development towards anti-inflammatory and antitumor therapies, pending further in vivo validation.