A Combinative Assembly Strategy Inspired Reversibly Borate-Bridged Polymeric Micelles for Lesion-Specific Rapid Release of Anti-Coccidial Drugs

HIGHLIGHTS: A combined assembly strategy from hydrophobicity-driving and reversible borate bridges is proposed for high drug-loading efficiency and superior stability. Intestinal environment-triggered drug delivery system represents an effective treatment for local infection due to the site-specific targeting and shuttling of drugs. The reduced dosage brought by the drug-loading micelles could solve the problem of drug residue in breeding industry. ABSTRACT: Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs. Herein, chitosan conjugates (SPCS) installed with sialic acid (SA) and phenylboronic acid (PBA) were synthesized, of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA. The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges. The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract. After reaching the lesions, the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release, while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside. The drug-micelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation. The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable, safe and flexible anti-infectious drug delivery systems. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40820-020-00495-1) contains supplementary material, which is available to authorized users.