Controlling Structure and Function of Polymeric Drug Delivery Nanoparticles Using Microfluidics

Abstract

We demonstrate control of multiscale structure and drug delivery function for paclitaxel (PAX)-loaded polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) polymeric nanoparticles (PNPs) via synthesis and flow-directed shear processing in a two-phase gas-liquid microfluidic reactor. This strategy takes a page from the engineering of commodity plastics, where processing rather than polymer chemistry provides an experimental handle on properties and function. PNPs formed from copolymers with three different PCL block lengths show sizes, morphologies, and loading efficiencies that depend on both the PCL block length and the microfluidic flow rate. By varying flow rate and comparing with a conventional bulk method of PNP preparation, we show that flow-variable shear processing provides control of PNP sizes and morphologies and enables slower PAX release times (up to 2 weeks) compared to bulk-prepared PNPs. Antiproliferative effects against cultured MCF-7 breast cancer cells were greatest for PNPs formed at an intermediate flow rate, corresponding to small and low-polydispersity spheres formed uniquely at this flow condition. Formation and flow-directed nanoscale shear processing in gas-liquid microfluidic reactors provides a manufacturing platform for drug delivery PNPs that could enable more effective and selective nanomedicines through multiscale structural control.

Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation

“…This result showed that the on‐chip flow rate hold the potential for tuning timed release of specific drugs for desired treatments. In a more recent work of Moffitt's group, the effects of PCL block lengths and flow rate on sizes, morphologies, and PTX‐loading efficiencies of PCL‐ b ‐PEO micelles were studied systematically.…”

Microfluidic encapsulation of SN-38 in block copolymer nanoparticles: effect of hydrophobic block composition on loading and release properties

“…14 Although the hydrolytic degradation of PCL makes it an appropriate in vivo host for a wide variety therapeutic molecules, its semicrystalline nature can strongly influence drug delivery properties. 15,16 For example, an increase in the crystallinity of the core-forming PCL blocks has been shown to increase drug release times in some studies. [15][16][17][18] However, crystallites can also exclude drug molecules leading to lower encapsulation efficiencies.…”

“…15,16 For example, an increase in the crystallinity of the core-forming PCL blocks has been shown to increase drug release times in some studies. [15][16][17][18] However, crystallites can also exclude drug molecules leading to lower encapsulation efficiencies. 15,16,18 In addition, SN-38 generally shows low solubility in aliphatic polyesters including PCL and PLGA.…”

“…[15][16][17][18] However, crystallites can also exclude drug molecules leading to lower encapsulation efficiencies. 15,16,18 In addition, SN-38 generally shows low solubility in aliphatic polyesters including PCL and PLGA. 11 Together these features highlight a need for studies involving systematic variation in block copolymer hydrophobic block composition and crystallinity, in order to gain insights en route to improved materials for SN-38 delivery systems.…”

Strategies for Drug Encapsulation and Controlled Delivery Based on Vapor‐Phase Deposited Thin Films

“…Drug‐loaded hydrogels can be directly injected in a minimally invasive way, thanks to their high moldability, and the ability to form tissue constructs in‐situ . Particularly interesting is the use of external stimuli to trigger the release of the drug at a specific site or specific time …”