Microneedle-Mediated Treatment of Obesity

Abstract

Obesity has become a major public health threat, as it can cause various complications such as diabetes, cardiovascular disease, sleep apnea, cancer, and osteoarthritis. The primary anti-obesity therapies include dietary control, physical exercise, surgical interventions, and drug therapy; however, these treatments often have poor therapeutic efficacy, significant side effects, and unavoidable weight rebound. As a revolutionized transdermal drug delivery system, microneedles (MNs) have been increasingly used to deliver anti-obesity therapeutics to subcutaneous adipose tissue or targeted absorption sites, significantly enhancing anti-obese effects. Nevertheless, there is still a lack of a review to comprehensively summarize the latest progress of MN-mediated treatment of obesity. This review provides an overview of the application of MN technology in obesity, focusing on the delivery of various therapeutics to promote the browning of white adipose tissue (WAT), suppress adipogenesis, and improve metabolic function. In addition, this review presents detailed examples of the integration of MN technology with iontophoresis (INT) or photothermal therapy (PTT) to promote drug penetration into deeper dermis and exert synergistic anti-obese effects. Furthermore, the challenges and prospects of MN technology used for obesity treatment are also discussed, which helps to guide the design and optimization of MNs. Overall, this review provides insight into the development and clinical translation of MN technology for the treatment of obesity.

Keywords: drug penetration; microneedle; obesity; prospect; treatment.

Figure 8

(a) Schematic representation of metformin delivery to subcutaneous WAT in obese C57BL/6J mice using a soluble PLGA MN assisted by INT to promote WAT browning and thermogenesis [104]. Reproduced with permission from [104]. Copyright 2022, Pharmaceutics. (b–d) Illustration of transdermal photothermal drug therapy using MN patches loaded with polydopamine NPs (PDA-NPs) and mirabegron to suppress adipogenesis and induce adipocyte browning. (b) Preparation process of the MN patch. (c) Step-by-step procedure for anti-obesity MN treatment. (d) Mechanism underlying the browning of WAT induced by the MN patch therapy [121]. Reproduced with permission from [121]. Copyright 2024, Biomaterials Science.

Figure 1

Schematic of various MN-mediated treatments for obesity.

Figure 2

(a) Schematic illustration of a gelatin MN system for transdermal delivery aimed at reducing local subcutaneous fat. (b–e) Analysis of mRNA and protein expression levels of lipogenic genes in isolated rat adipocytes treated with three different polymers: gelatin, hyaluronic acid (HA), and collagen. Rat pre-adipocytes were differentiated into adipocytes using DIM media and subsequently exposed to polymers (0.1 mg/mL) for 24 h (* p < 0.05 compared to the DIM group; ^# p < 0.05 compared to the Con group). Transcription levels of lipogenic markers FASN (b), SREBP-1c (c), and PPARγ (d) were assessed by quantitative real-time qPCR and Western blotting (e) [45]. Reproduced with permission from [45], Copyright 2018, Acta Biomaterialia. (f) Hematoxylin and eosin (H&E) staining of subcutaneous adipose tissue treated with MN patches [46]. Reproduced with permission from [46] Copyright 2019, Toxicology Research.

Figure 3

(a) Schematic representation of a multifunctional MN patch (MNP) incorporating Cap-loaded micelles designed to suppress adipogenesis and induce adipocyte browning. (b) Body weight progression of HFD-induced obese mice was monitored at specific time points following treatment with MP-M, MP-CAP, MP-M(CAP), and InJ-M(CAP) (** p < 0.01). (c) The relative weight of inguinal white adipose tissue (iWAT) in the treated groups was normalized to that of untreated HFD-induced obese mice (* p < 0.05, and *** p < 0.001) [60]. Reproduced with permission from [60] Copyright 2021, Advanced Functional Materials.

Figure 4

(a) Conceptual illustration of the application and mechanism of LGP-MN. (b,c) Detailed schematic explanation of the mechanism and application of LGP-MN (n = 7–8, ** p < 0.01, and *** p < 0.001). (d) Ultrasound images showing gastric volume changes two weeks post-BTX-A treatment. (e) Statistical analysis of gastric emptying rates measured via ultrasound [69]. Reproduced with permission from [69] Copyright 2023, Advanced Science.

Figure 5

(a) Schematic representation of the design of vascular-targeted NPs (PTNP: prohibitin-targeted NPs). (b) Illustration of the enhanced targeting of PTNP to white fat vasculature (WFV) in diet-induced obese (DIO) mice through active and passive mechanisms (scale bars: 100 μm). (c) Diagram of the dual mechanisms—active and passive targeting—enabling improved drug delivery of PTNP into obese adipose tissue [79]. Reproduced with permission from [79] Copyright 2012, Journal of Controlled Release. (d) Schematic depiction of dual-targeted Rs-NPs promoting the browning of WAT. (e) Conceptual design of three types of NPs. (f) Histological analysis of iWAT (upper panel, scale bars: 100 μm) and liver tissue (lower panel, scale bars: 50 μm) stained with H&E following administration of free Rosi and various Rs-NPs; representative images of excised livers are presented at the conclusion of the treatment period [84]. Reproduced with permission from [84] Copyright 2021, Journal of Controlled Release.

Figure 6

(a,b) Schematic illustration of an MN patch integrated with browning reagents. NPs encapsulating Rosi, GOx, and CAT are synthesized using pH-sensitive dextran functionalized with acetal linkages and encapsulated with alginate. These NPs are incorporated into a MN-array patch composed of a HA matrix stabilized through cross-linking for inducing browning in WAT [18]. Reproduced with permission from [18] Copyright 2017, ACS Nano. (c) Mechanistic diagram of the soluble nanoparticle MN patch for obesity treatment [86]. Reproduced with permission from [86] Copyright 2024, Biomaterials.

Figure 7

(a) Schematic representation of the ultrarapid-acting MN (URA-MN) patch, engineered to facilitate the immediate delivery of biotherapeutics. (b) Dissolution kinetics of LRT from diverse MN patches, with each group comprising three replicates (n = 3, ** p < 0.01, and *** p < 0.001). (c) Plasma glucose levels in db/db mice (n = 5) treated daily with saline, subcutaneous LRT injection (1.00 mg/kg), or MN patches (1.73 mg/kg) over six weeks. (d) Body weight changes in db/db mice (n = 5) monitored over the same period [92]. Reproduced with permission from [92] Copyright 2023, Advanced Materials.