Multimodal delivery of irinotecan from microparticles with two distinct compartments

Abstract

In the last several decades, research in the field of drug delivery has been challenged with the fabrication of carrier systems engineered to deliver therapeutics to the target site with sustained and controlled release kinetics. Herein, we report the fabrication of microparticles composed of two distinct compartments: i) one compartment containing a pH responsive polymer, acetal-modified dextran, and PLGA (polylactide-co-glycolide), and ii) one compartment composed entirely of PLGA. We demonstrate the complete release of dextran from the microparticles during a 10-hour period in an acidic pH environment and the complete degradation of one compartment in less than 24 h. This is in congruence with the stability of the same microparticles in neutral pH over the 24-hour period. Such microparticles can be used as pH responsive carrier systems for drug delivery applications where their cargo will only be released when the optimum pH window is reached. The feasibility of the microparticle system for such an application was confirmed by encapsulating a cancer therapeutic, irinotecan, in the compartment containing the acetal-modified dextran polymer and the pH dependent release over a 5-day period was studied. It was found that upon pH change to an acidic environment, over 50% of the drug was first released at a rapid rate for 10 h, similar to that observed for the dextran release, before continuing at a more controlled rate for 4 days. As such, these microparticles can play an important role in the fabrication of novel drug delivery systems due to the selective, controlled, and pH responsive release of their encapsulated therapeutics.

Electrohydrodynamic atomization: A two-decade effort to produce and process micro-/nanoparticulate materials

“…Further in vivo study suggested that intravenous injection of these microparticles into mice inoculated with Leishmania can significantly eliminate parasite load in the bone marrow versus controls. Rahmani et al (2013) investigated the pH-responsive delivery of irinotecan from microparticles having two different compartments generated by side-by-side electrospray. Bai and Liu (2014) prepared cisplatin-loaded maleimide-PEG-PLGA particles using EHDA and subsequently conjugated with CD44 antibody.…”

Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

“…In the past, we have used the EHD co-jetting technique to fabricate particles from various types of polymers in order to realize different degradation kinetics and/or on-demand capabilities, such as pH-responsive or dual-responsive particles with oxidative and UV triggers, which can be used to control the degradation and release of combinations of therapeutics [23–25]. The incorporation of small molecular weight therapeutics, as well as siRNA and other biomacromolecules, into these multicompartmental particles and their distinct release kinetics have also been studied [23,24,26–28].…”

“…The incorporation of small molecular weight therapeutics, as well as siRNA and other biomacromolecules, into these multicompartmental particles and their distinct release kinetics have also been studied [23,24,26–28]. Moreover, we have demonstrated the selective and orthogonal surface modification of distinct patches of the particles’ surface for incorporation of targeting, stealth or therapeutic moieties [28–32].…”

CXCR4-Targeted Nanocarriers for Triple Negative Breast Cancers

“…27,28 If responsive bulk materials are used, carriers can be designed to respond to environmental changes, such as light, oxidative stress, or local pH. 25,28 Chemically reactive polymers may also be incorporated in selected compartments for selective surface conjugation of targeting moieties. 29 …”