Dissolving Microneedles with Spatiotemporally controlled pulsatile release Nanosystem for Synergistic Chemo-photothermal Therapy of Melanoma

Abstract

High aggressiveness and recurrence of melanoma tumors require multiple systemic drug administrations, causing discomfort and severe side effects to the patients. Topical treatment strategies that provide repetitively controllable and precise drug administrations will greatly improve treatment effects. Methods: In this study, a spatiotemporally controlled pulsatile release system, which combined dissolving microneedles (DMNs) and thermal-sensitive solid lipid nanoparticles (SLNs), was constructed to realize multiple doses of dual-modal chemo-photothermal therapy in a single administration. Paclitaxel (PTX) and photothermal agent IR-780 were encapsulated into SLNs and were concentrated in the tips of DMNs (PTX/IR-780 SLNs @DMNs). Equipped with several needles, the DMN patch could be directly inserted into the tumor site and provide a stable “Zone accumulation” to constrain the PTX/IR-780 SLNs at the tumor site with uniform distribution. Results: In vitro experiments showed that after irradiation with near-infrared light, the PTX/IR-780 SLNs gradually underwent phase transition, thereby accelerating the release of PTX. When irradiation was switched off, the PTX/IR-780 SLNs cooled to re-solidify with limited drug release. Compared with intravenous and intratumoral injections, very few SLNs from PTX/IR-780 SLNs @DMNs were distributed into other organs, resulting in enhanced bioavailability at the tumor site and good safety. In vivo analysis revealed that PTX/IR-780 SLNs @DMNs exhibited significant anti-tumor efficacy. In particular, the primary tumor was completely eradicated with a curable rate of 100% in 30 days and the highest survival rate of 66.67% after 100 days of treatment. Conclusion: Herein, we developed a DMN system with a unique spatiotemporally controlled pulsatile release feature that provides a user-friendly and low-toxicity treatment route for patients who need long-term and repeat treatments.

A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy

“…Previous reports have shown that the enhanced outcomes of combinational treatment with PTX and IR780 were associated with the promotion of tumor cell apoptosis via a prolonged G2 phase of the cell cycle and ROS-mediated PDT, which were in agreement with our findings [ 38 , 39 ]. Following exposure to NIR, PTX/IR780-HA&RBCm-LCNPs successfully induced A549 cells to produce a large amount of ROS, whereas without NIR irradiation, no obvious ROS production was observed (Fig.…”

“…Photochemotherapy produced by the combination of PTX and IR780 has been shown to enhance antitumor effects [ 38 ]. For example, the cure rate of primary melanoma-bearing mice with intratumoral injection was 100% within 30 days [ 39 ]; IR780 was able to exert photothermal therapeutic effects on pancreatic ductal adenocarcinoma and expanded the tumor interstitial space to promote paclitaxel delivery to deep tumor tissues [ 40 ]. However, IR780 is a NIR-I near-infrared photosensitizer with a limited tissue-penetrating depth [ 41 ].…”

Recent Advances in Nanotechnology for the Treatment of Melanoma

“…Furthermore, the MNs only penetrate the epidermal layer without damaging the neurons and capillaries in the dermis, thereby minimizing the pain associated with transdermal administration and without causing skin damage and bleeding [ 84 ]. Huang et al has first synthesized a dextran methacrylate hydrogel (DexMA) to develop a new type of NMs for continuous transdermal administration of doxorubicin (DOX) and trametinib (Tra) two FDA-approved anticancer drugs [ 85 ]. The antitumor efficacy in nude mice xenograft of B16 cells was evaluated by highlighting the synergistic anticancer effects of DOX and Tra.…”

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

“…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].…”