Stimuli-responsive attachment for enabling the targeted release of carriers

Abstract

Targeted release of drugs is important for precision treatment at the desired site and preventing the indiscriminate release of drugs. Incorporating stimuli-responsiveness into drug carriers has been proposed to enable the carriers to have the ability to perform targeted release at specific sites. However, a vast majority of the many established carriers are not stimuli-responsive. The current methods used for the synthesis of stimuli-responsive carriers are mostly highly specific and ineffective (e.g., they either leak or cannot release completely). This manuscript describes a novel class of stimuli-responsive attachments that can be attached flexibly onto any type of soft carrier (i.e., loaded with chemicals or drugs), thus transforming the non-responsive carrier into a stimuli-responsive carrier. The attachment consists of a layer of stimuli-responsive hydrogel around the carrier and a partial rigid coating on the exterior. The attachment is general: non-responsive carrier materials of different types (e.g., liposomes and polymeric carriers) and different sizes (e.g., nanoscale and macroscopic) are shown to become stimuli-responsive for different types of stimuli. Importantly, the attachment is capable of exerting a large pressure for rupturing carriers with rigid and impermeable shells (e.g., highly crosslinked shells). Hence, these carriers with stimuli-responsive attachment effectively exhibit a full range of stimuli-responsiveness: they are not leaky due to their rigid shells, but can release their contents completely via rupture of their shells under the influence of the stimulus. The approach of using this novel class of stimuli-responsive attachments is thus general, simple, and effective. The large number and diverse range of well-established soft non-responsive drug carriers can be transformed into stimuli-responsive carriers conveniently without the constant need to find specific methods for different types of carriers.