OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment.
METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week.
RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88% for Group A, 62% for Group B, and 36% for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time.
CONCLUSIONS: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

The lack of in vivo studies on the delivery of doxorubicin within human skin, especially the absence of data on the doxorubicin diffusion coefficient, has made understanding its transdermal delivery kinetics challenging. In this study, as a first step, governing equations and finite element methods were employed to reproduce Franz diffusion cell experiment in human cadaver skin. The application of this experiment representative model with a fitting method resulted in approximate values for the diffusivity of doxorubicin across various skin layers. The estimated values were used later to conduct a comprehensive examination of doxorubicin administration for breast tumor treatments. In a 2D axisymmetric model using Fick\'s Law and then a microneedles array 3D model, crucial parameters effects on delivery efficiency were examined, such as the microneedle tip diameter, tip-to-tip distance, and tumor depth. As highlighted by the findings of this study, these parameters have an impact on the effectiveness of doxorubicin delivery for treating breast tumors. The focus of this research is on the potential of numerical methods in biomedical engineering, which addresses the urgent need for data on doxorubicin diffusion in human skin and offers valuable insights into optimizing drug delivery strategies for enhanced therapeutic outcomes.

Recently, several clinical studies have been conducted using microneedles (MNs), and various devices have been developed. This study aimed to propose and confirm the feasibility of a placebo control for activating MN clinical research. A 0.5 mm MN stamp with 42 needles was used as a treatment intervention, and a placebo stamp with four acupressure-type needles that did not penetrate was proposed and designed as a control for comparison. First, to check whether the placebo stamp did not invade the skin and to set an appropriate level of pressure to be provided during skin stimulation, two participants were stimulated with five different forces on the forearm, and then the skin was dyed. Secondly, to evaluate the validity of the placebo control group, a blinded study between the MN and placebo stamps was performed on 15 participants. We confirmed that the placebo stamp did not penetrate the skin at any intensity or location. Both types of stamps reported relatively low pain levels, but the MN stamp induced higher pain compared to the placebo stamp. Based on the speculation regarding the type of intervention received, the MN stamp was successfully blinded (random guess), whereas the placebo stamp was unblinded. However, according to a subgroup analysis, it was confirmed that the group with low skin sensitivity was completely blind. Blinding the placebo MN stamp had limited success in participants with low skin sensitivity. Future research on suitable placebo controls, considering the variations in MN stamp length and needle count, is warranted.

In this paper, a roadmap is provided for the regulatory approval of one of the exciting and dynamic drug delivery fields, microneedles, by using a Quality by Design approach to pharmaceutical product development. In this regard, a quality target product profile (QTPP) and the critical quality attributes (CQA) of microneedles are identified. A case study of the recently patented method of fabricating glass microneedles entirely from a therapeutic agent, thus eliminating the requirement for additional excipients is discussed. The glass microneedle, ArrayPatch, is a propriety wearable device with platform potential consisting of an array of sharp, but painless, dissolvable microneedles manufactured with 100% drug. The microneedles penetrate the skin on application and dissolve to deliver a locally effective dose. The in vitro characterization of the microneedle CQAs under WHO-guided stability conditions will be described to assess the manufacturing readiness of ArrayPatch.  A live technical video is also provided, presenting a unique procedure of jugular vein cannulation through the ear vein of a pig animal model to study the in vivo pharmacokinetics of ArrayPatch compared to standard-of-care marketed products.

Biodegradable microneedles with a drug delivery channel have enormous potential for consumers, including use in chronic disease, vaccines, and beauty applications, due to being painless and scarless. This study designed a microinjection mold to fabricate a biodegradable polylactic acid (PLA) in-plane microneedle array product. In order to ensure that the microcavities could be well filled before production, the influences of the processing parameters on the filling fraction were investigated. The results indicated that the PLA microneedle can be filled under fast filling, higher melt temperature, higher mold temperature, and higher packing pressure, although the dimensions of the microcavities were much smaller than the base portion. We also observed that the side microcavities filled better than the central ones under certain processing parameters. However, this does not mean that the side microcavities filled better than the central ones. The central microcavity was filled when the side microcavities were not, under certain conditions in this study. The final filling fraction was determined by the combination of all parameters, according to the analysis of a 16 orthogonal latin hypercube sampling analysis. This analysis also showed the distribution in any two-parameter space as to whether the product was filled entirely or not. Finally, the microneedle array product was fabricated according to the investigation in this study.

The aim of this study is to design and evaluate a transdermal delivery system for alendronate sodium (ALS) loaded with nanocarrier to improve its permeability and prolong its release. This is due to its low bioavailability, potential gastrointestinal side effects, and the special administration needed for the oral dosage form of ALS. When using the ether injection method, various niosomal formulations were produced. Size of the particles, polydispersity index (PDI), surface charge (ZP), drug entrapment efficiency (EE), and in vitro release were used to characterize the resulting niosomes. The size of niosomes ranged between 99.6 ± 0.9 and 464.3 ± 67.6 nm, and ZP was from −27.6 to −42.27 mV. The niosomal formulation was then loaded to aqueous polymer solution of 30% polyvinyl pyrrolidone (PVP) (MN-1), 30% PVP with 15% poly(vinyl alcohol) (PVA) (2:1) (MN-2), and 30% PVP with 15% PVA (1:1) (MN-3). The cumulative amount of ALS (Q) was in the following order: MN-1 > MN-2 > MN-3. All formulations in this study were stable at room temperature over two months, in terms of moisture content and drug content. In conclusion, a transdermal delivery of ALS niosomes combined in microneedles (MNs) was successfully prepared to provide sustained release of ALS.

Microneedles have the clinical advantage of being able to deliver complex drugs across the skin in a convenient and comfortable manner yet haven\'t successfully transitioned to medical practice. Diabetes mellitus is a complicated disease, which is commonly treated with multiple daily insulin injections, contributing to poor treatment adherence. Firstly, this review determines the clinical prospect of microneedles, alongside considerations that ought to be addressed before microneedle technology can be translated from bench to bedside. Thereafter, we use diabetes as a case study to consider how microneedle-based-technology may be successfully harnessed. Here, publications referring to insulin microneedles were evaluated to understand whether insertion efficiency, angle of insertion, successful dose delivery, dose adjustability, material biocompatibility and therapeutic stability are being addressed in early stage research. Moreover, over 3,000 patents from 1970-2019 were reviewed with the search term \'\"microneedle\" AND \"insulin\"\' to understand the current status of the field. In conclusion, the reporting of early stage microneedle research demonstrated a lack of consistency relating to the translational factors addressed. Additionally, a more rational design, based on a patient-centred approach is required before microneedle-based delivery systems can be used to revolutionise the lives of people living with diabetes following regulatory approval.

Interstitial fluid (ISF) provides important information of clinical value and physiological significance beyond blood tests for obtaining more precise health information and disease theranostics. Generally, current strategies are limited to simple extraction with time-consuming follow-up procedures. Facing challenges in efficient and real-time monitoring of target analytes in transdermal ISF, we develop metal-organic framework (MOF)-functionalized microneedle (MN) patches to achieve efficient antibiotics sampling, coupling direct analysis in real time mass spectrometry (DART-MS). The MOF MN microtrapper is constructed in a double-layered structure with a hard core and a better tissue penetration was accomplished. The MOF-based microtrapper manifests good in-vitro and in-vivo antibiotics tracking capability with a semi-quantitative method established. Moreover, the hydrogen-bond driven interaction is clarified by using molecular dynamics simulations (MDS) and related computational analysis. Good penetration safety is confirmed by histological analysis with promising clinical transnationality. We anticipate MOF MN-based microdevices provide a versatile minimally invasive strategy for transdermal ISF extraction and an extendable platform for a range of target molecules monitoring, including drugs, metabolites, biomarkers, et c, with promising clinical transnationality.

The objective of the present study was to evaluate discomfort and safety of microneedle (MN) insertion in several intraoral regions. A device was developed to standardize MN insertions. MNs were inserted in the following regions of the oral cavity: gingiva, palatine alveolar process, buccal mucosa, dorsum of the tongue and inner portion of the lower lip. Perforations from MNs post insertion were confirmed with topical gentian violet stain. Pain was evaluated in a randomized, double-blinded, crossover study in 30 volunteers. Each volunteer received a MN patch, a 30G hypodermic needle (positive control) and an identical MN patch with its needles laying flat in the plane of the patch (negative control). Adverse events were visually evaluated immediately after (0 h) and 24 h post MN application. The application device developed a consistent application force (10 N) and promoted perforation of all individual MNs on a patch. At all sites, insertion of the hypodermic needle promoted more pain when compared to the negative control (p < 0.001). Application of the MNs promoted less pain than the hypodermic needle (p < 0.05), but slightly more pain as compared to the negative control (p < 0.05) at all sites except the tongue, where the MN did not differ from the negative control (p > 0.05). Hypodermic needle caused bleeding at all insertion sites. In contrast, MNs did not cause bleeding at most sites except in some cases of insertion into the hard gingiva and the palatine alveolar process where tiny blood spots appeared immediately after MN application for few of the MNs on the patch. There were no cases of bleeding at 24 h post MN application. In conclusion, MNs can perforate different sites of the oral cavity in a safe and significantly less painful manner as compared to the 30G hypodermic needle. Thus, analogous to the skin, MN-based approaches could be an attractive approach for drug delivery in the oral cavity.

The presence of bacterial biofilms in wounds is a main issue in the healing process. Conventional therapy of bacterial biofilms is hampered by the poor penetration of antibacterial agents through the physical barrier on the infected skin and the non-specific target of antibacterial agents. Here, we present a combination approach of bacterial sensitive nanoparticles (NPs) and dissolving microneedles (MNs) of doxycycline (DOX) for improved biofilm penetration and specifically delivering DOX to the infection site. The NPs were prepared from poly(lactic-co-glycolic acid) and poly (Ɛ-caprolactone) decorated with chitosan. The release of DOX was improved with the presence of bacterial producing biofilm up to 7-fold. The incorporation of these NPs into dissolving MNs was able to significantly enhance the dermatokinetic profiles of DOX, indicated by higher retention time compared to needle-free patches. Importantly, the antibiofilm activity in ex vivo biofilm model showed that after 48 h, the bacterial bioburdens decreased up to 99.99% following the application of this approach. The results presented here assist as proof of principle for the improvement of dermatokinetic profiles and antibiofilm activities of DOX, following its formulation into bacterial sensitive NPs and delivery via MN. Future studies must explore in vivo efficacy in a suitable animal model.