Dissolving Microneedles Loading TPGS Biphasic Functionalized PLGA Nanoparticles for Efficient Chemo‐Photothermal Combined Therapy of Melanoma

Abstract

The poly (lactic‐co‐glycolic acid) nanoparticle (PLGA NP) has been widely used in the biomedical field. However, it is insensitive to degradation upon laser irradiation, resulting in a limited increase in drug release, which compromises the therapeutic efficacy. To actively promote drug release, the biphasic α‐tocopheryl succinate (TPGS) functionalized PLGA NPs (PTNPs) are developed by introducing TPGS into the aqueous and organic phase to generate pores in the PLGA core during preparation. Paclitaxel and indocyanine green are encapsulated in the PTNPs to realize chemo‐photothermal combined therapy, and PTNPs are delivered through dissolving microneedles (DMNs) for local treatment in melanoma. PTNPs show enhanced drug release and improved cytotoxicity due to their greater ability in inhibiting cell microtubule depolymerization. In vivo tumor suppression investigation and ki‐67 immunohistochemical staining of tumor tissue further show the superiority of PTNPs loaded DMNs against tumor growth, and photothermal therapy synergistically enhances the chemotherapeutic effect of PTNPs. Moreover, the living imaging of mice demonstrates that the drug is successfully retained in the tumor tissue to avoid it entering into the circulation and producing adverse effects. Therefore, the PTNPs loaded DMNs show a favorable prospect in the treatment of superficial tumor.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

“…DMNs were prepared by a stepwise centrifugation method to concentrate the NPs in the tip of needles and increase the dug loading of DMNs ( Fig. 1 ) 27 . The detailed procedure and characterization of DMNs in terms of morphology, skin insertion ability, and photothermal conversion efficiency are provided in the Supporting Information .…”

Dissolving Microneedles Developed in Association with Nanosystems: A Scoping Review on the Quality Parameters of These Emerging Systems for Drug or Protein Transdermal Delivery

“…Likewise, 60.0% of the studies that aimed at antibacterial activity applied the device in a biofilm model [37][38][39]. Overall, the results showed in Figure 2D suggest greater investment in diseases that affect the immune system, prioritizing transcutaneous immunization and the management of psoriasis [40][41][42], superficial tumors [32][33][34][35][36]43], and diseases that affect the lymphatic system owing to its proximity to the systemic circulation, such as filariasis [22,44,45]. Above all, diabetes mellitus, which requires constant insulin administrations, was prioritized [20,46,47].…”

“…Additionally, the highest percentage of studies were conducted to validate a proof of concept for transcutaneous immunization (n = 20) or to validate the delivery mechanism of drugs and substances (n = 15), followed by diabetes management (n = 10), as shown in Figure 2D. Looking into the studies that evaluated antitumoral activity, the most used preclinical model comprised melanoma cell lines, accounting for 66.8% of this category [32][33][34][35][36]. Likewise, 60.0% of the studies that aimed at antibacterial activity applied the device in a biofilm model [37][38][39].…”

“…The sample preparation procedure consisted of the complete dissolution of the devices in distilled water, buffer, or mixtures with organic solvent and subsequent quantification [64,67]. For devices composed of at least two polymer layers, in which the nanostructured system was located only in the needle, whereas the baseplate was formed by an inert polymeric structure, the studies described the removal of the microneedles with a scalpel and only the needles were dissolved for analysis [33,34,38,51,52,68,69]. Images of the needles removed for testing and the remaining baseplate are shown in the article by Li et al [68].…”

“…In complement to the device formed by the combination of dissolvable polymers and a nanostructured system, the drug and protein release process can be promoted through external stimuli such as iontophoresis and magnetism fields as well as be applied to potentiate the therapy as near-infrared-light (NIR). Among the studies included in this review, only eight described the use of external stimuli, of which five studies corresponded to NIR [33][34][35][36]43], one to photodynamic therapy [85], one to iontophoresis [23], and one to magnetic fields [66]. The tests performed to evaluate the effects of these stimuli on the nanostructured systems and devices are presented in Table S2.…”