The Effect of Drug Heterogeneous Distributions within Core-Sheath Nanostructures on Its Sustained Release Profiles

The sustained release of a water-soluble drug is always a key and important issue in pharmaceutics. In this study, using cellulose acetate (CA) as a biomacromolecular matrix, core-sheath nanofibers were developed for providing a sustained release of a model drug—metformin hydrochloride (MET). The core–sheath nanofibers were fabricated using modified tri-axial electrospinning, in which a detachable homemade spinneret was explored. A process—nanostructure–performance relationship was demonstrated through a series of characterizations. The prepared nanofibers F2 could release 95% of the loaded MET through a time period of 23.4 h and had no initial burst effect. The successful sustained release performances of MET can be attributed to the following factors: (1) the reasonable application of insoluble CA as the filament-forming carrier, which determined that the drug was released through a diffusion manner; (2) the core–sheath nanostructure provided the possibility of both encapsulating the drug completely and realizing the heterogeneous distributions of MET in the nanofibers with a higher drug load core than the sheath; (3) the thickness of the sheath sections were able to be exploited for further manipulating a better drug extended release performance. The mechanisms for manipulating the drug sustained release behaviors are proposed. The present proof-of-concept protocols can pave a new way to develop many novel biomolecule-based nanostructures for extending the release of water-soluble drugs.

Bioinspired Adhesive and Antibacterial Microneedles for Versatile Transdermal Drug Delivery

Microneedles have attracted increasing interest among various medical fields due to their painless, noninvasive, and efficient way of drug delivery. However, practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity. Here, inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles, we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities. With polydopamine hydrogel as the microneedle base and a loop of suction-cup-structured concave chambers encircling each microneedle, the generated microneedles can fit the skin well; keep strong adhesion in dry, moist, and wet environments; and realize self-repair after being split into two parts. Besides, as polymyxin is loaded into both the hydrogel tips and the polydopamine base, the microneedles are endowed with excellent ability to resist common bacteria during storage and usage. We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model. These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems.