Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics

Abstract

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Synthesis and characterization of thermosensitive poly(N-vinylcaprolactam)-g-collagen

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Prevention of Obesity Related Diseases through Laminarin-induced targeted delivery of Bindarit

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Twisted Intramolecular Charge Transfer—Aggregation-Induced Emission Fluorogen with Polymer Encapsulation-Enhanced Near-Infrared Emission for Bioimaging

“…According to previous studies, hydrophobic dyes encapsulated by amphiphilic copolymers can enter the hydrophobic segment of the copolymer via hydrophobic-hydrophobic interactions. [51][52][53] Therefore, we employed a molecular simulation approach to investigate the interaction between TB-TPE and the polymer matrix, using TB-TPE/PS as a model system. As shown in Figure 5a, the PS segment provides a hydrophobic nonpolar environment, and TB-TPE molecules are easily dispersed into the PS matrix, based on atomistic molecular dynamics (MD) simulations (Figure 5b).…”