Pollen-inspired microparticles with strong adhesion for drug delivery

Abstract

Microparticles with strong adhesion property was presented as efficacious drug delivery systems. Here, inspired by natural pollen, polymer microparticles with surface textures and homogeneous size were fabricated through evaporation-induced interfacial instability of microfluidic droplets templates. The resultant particles exhibited controllable surface roughness and thus strong adhesion ability to the intestinal mucosa. Such particles were employed as novel drug carriers, which contributed to enhanced loading efficacy and controllable release kinetics, and were proved to increase therapeutic effectiveness through in vivo and in vitro tests, thus playing a potential role in sustained drug delivery, bioimaging, diagnostics, etc.

Introduction

Microparticles with different sizes, morphology, and surface properties are among the most promising systems for targeted and controlled drug delivery and noninvasive drug administration [1], [2], [3], [4], [5]. By encapsulating therapeutic agents into microspheres or microcapsules, these particles serve as vehicles for the delivery of proteins, peptides, and small molecule drugs [6], [7], [8], [9], [10], [11], [12], [13], [14]. Fabrication of drug-loaded microparticles could be achieved through emulsion droplets templates, which are conventionally derived by various approaches including mechanically stirring [15], membrane emulsification [16], sonication [17], etc. However, particles obtained from these methods typically show high polydispersity, which are not conducive to controlling the amounts of drug loading and verifying the kinetics of drug release, therefore imposing limitations on the wide applications of these drug-loaded particles [18], [19], [20]. Besides, current drug microcarriers possess relatively simple surface structure and lack certain physicochemical properties and functions, such as adhesion ability [21], [22], [23]. This reduces drug delivery efficiency because insufficient adhesion of the carriers to the target results in rapid decrease of drug concentration and thus low sustainability [24]. Therefore, generating microparticles with homogeneous size distribution and strong adhesion property is highly in demand for constructing efficient drug delivery systems.

Natural plant pollen has emerged as promising micro-carriers for drug encapsulation [25]. In this paper, inspired by the strong adhesion of pollen to the respiratory tract and interactions with mucosa due to its coarse surface morphology (Fig. 1a) [26], [27], we present a novel biodegradable particles with tunable surface textures as adhesive drug carriers via microfluidics, as shown in Fig. 1b. Due to their capability of generating monodisperse droplet templates and executing precise control over the physical and chemical processes during particles formation, microfluidic technology has become a crucial tool for controllable fabrication of microparticles with complex structures and desired functions [28], [29], [30], [31], [32], [33], [34], [35], [36]. However, microfluidic fabrication of microparticles with strong adhesion function for drug delivery is seldom reported. Herein, we used microfluidics to generate uniform droplets containing biocompatible polymers and a volatile solvent. Along with the evaporation of the solvent, shrinking droplets triggered interfacial instabilities to shape into microparticles with surface textures, the roughness of which could be controlled through various parameters. Adhesion ability tests showed that the stickiness of the particles displays a substantial positive correlation with surface roughness. These particles were then employed as carriers by loading drugs into the polymer matrix and were further interacted with human colon cancer cells and intestinal inflammation sites, respectively. The results from in vitro studies revealed that the porous rough surface morphography of microparticles could fast and durably release drugs to inhibit tumor cell growth. Meanwhile, in vivo studies reflected the strong adhesion of drug-loaded microparticles and hollows on their surface synergistically acted on attenuating symptoms of Crohn's disease. Also, convenience on controlling pharmacokinetics at the lesions makes these microparticles potentially ideal for sustained drug delivery, bioimaging, biodiagnostics, etc.