With improvement in living condition and changes in lifestyle, obesity has become a global epidemic problem [1, 2]. Obesity may result in various comorbidities, with the most relevant being diabetes mellitus, arterial hypertension, cardiovascular diseases and non-alcoholic fatty liver disease [3, 4]. Currently, obesity treatment mainly includes physiotherapy, partial lipotomy and pharmacotherapy [5]. Pharmacotherapy has been more widely used in the treatment of obesity, e.g., treatment with orlistat, liraglutide, topiramate and so on. However, most of chemicals have been reported to show serious adverse effects after long-term use, for example, orlistat capsule is associated with several mild-to-moderate adverse gastrointestinal effects, such as oily stools, diarrhea, abdominal pain, fecal spotting and hepatitis [6]. Therefore, it is necessary to develop much safer anti-obesity drugs.
Emodin was found in Rheum tanguticum, Aloe barbadensis, Polygonum cuspidatum and other plants, and it has shown a variety of pharmacological effects, such as anti-tumor, anti-inflammatory, and anti-viral effects [7, 8]. Notably, Tzeng reported that emodin caused dose-related reductions in the size of epididymal white adipose tissue in high-fat diet-fed rats, which may be related to the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), upregulation of carnitine palmitoyl transferase 1 (CPT-1) expression, and downregulation of sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase protein (FAS) levels [9]. Lipolysis, a key process of lipid catabolism, is highly regulated by lipases such as hormone-sensitive lipase (HSL) and lipoprotein lipase LPL [10,11].
Most weight-loss preparations are orally administrated, which often results in first-pass effect that destroy the active ingredient before it enters the systemic circulation [], and some drugs that act on the gastrointestinal tract could cause diarrhea or constipation, for example, sennosides or rhubarb anthraquinones can cause diarrhea after long-term oral administration [13]. The transdermal drug delivery system (TDDS) is a noninvasive type of preparation in which drugs enter the skin and pass through the epidermis, dermis, and subcutaneous tissues. Compared with oral drug delivery, TDDS has many advantages, e.g., avoiding first-pass effects, improving bioavailability, relieving adverse reactions [14]. What is more beneficial is that patients who take TDDSs are more likely to self-adjust the dose and time of administration according to the practical clinical needs. Additionally, TDDSs can provide sustained release of drug, resulting in long-acting efficiency and lower toxicity [15].
In recent years, some advanced drug delivery systems and permeation promotion technologies were applied into TDDS preparations, such as nanocarriers, liposomes and transfersomes, microneedles (MNs) [16]. MNs can pierce the stratum corneum of skin to deliver of small drugs, macromolecules, and microparticles into the corium layer, while do not significantly damage skin [17]. MNs have been used in anti-obesity studies, for instant, Xie et al. performed transdermal delivery of anti-obesity drugs to evaluate the effectiveness of the β3 adrenergic receptor CL316243 in overweight mice induced by a high-fat diet [18]. Zhang et al. developed a technique based on a nanoparticle-integrated MN patch that enabled local browning of white adipose tissue (WAT). The degradable NPs released browning agents into the subcutaneous region in the presence of glucose and promoted the transformation of WAT toward brown-like adipose tissue [19]. Polydopamine (PDA), a dopamine-derived synthetic eumelanin polymer that contains catechol, imine, and amine groups, has a large surface area and high pore volume, resulting in good adhesion, biocompatibility, photothermal conversion properties [20]. Nowadays, it was widely utilized in the construction of drug loaded nanosphere for improved photothermal performance [21-22].
Here, an emodin-polyvinylpyrrolidone (PVP) co-precipitate was prepared to increase the solubility of emodin, which was then dissolved in a soluble MN matrix consisting of PVP, silk protein, and hyaluronic acid (HA) to form emodin-loaded MNs (PDA-Emodin-PV-MN). PDA was specially introduced into the emodin-loaded MNs, effectively motivating the release of emodin from the matrix and enhancing emodin penetration efficiency into the corium layer upon NIR irradiation. Meanwhile, high-temperature stimulation also accelerates the consumption of body fat to benefit the ultimate goal of weight-reducing. Comprehensive evaluation of the soluble PDA-Emodin-PVP-MN patches was conducted, including characterization with infrared spectrum and X-ray powder diffraction, weight-reducing effect and safety using a high-fat diet induced obese rat model, and possible mechanism of action at gene and protein levels was preliminarily explored.