Abstract

Conventional drug administration usually faces the problems of degradation and rapid excretion when crossing many biological barriers, leading to only a small amount of drugs arriving at pathological sites. Therapeutic drugs delivered by drug delivery systems to the target sites in a controlled manner greatly enhance drug efficacy, bioavailability, and pharmacokinetics with minimal side effects. Due to the distinct advantages of microfluidic techniques, microfluidic setups provide a powerful tool for controlled synthesis of drug delivery systems, precisely controlled drug release, and real-time observation of drug delivery to the desired location at the desired rate. In this review, we present an overview of recent advances in the preparation of nano drug delivery systems and carrier-free drug delivery microfluidic systems, as well as the construction of in vitro models on-a-chip for drug efficiency evaluation of drug delivery systems. We firstly introduce the synthesis of nano drug delivery systems, including liposomes, polymers, and inorganic compounds, followed by detailed descriptions of the carrier-free drug delivery system, including micro-reservoir and microneedle drug delivery systems. Finally, we discuss in vitro models developed on microfluidic devices for the evaluation of drug delivery systems, such as the blood–brain barrier model, vascular model, small intestine model, and so on. The opportunities and challenges of the applications of microfluidic platforms in drug delivery systems, as well as their clinical applications, are also discussed.

Highlights

  • Many therapeutic drugs might face problems such as low biodistribution, limited solubility, poor absorption, and drug aggregation

  • Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

  • Carrier-free direct drug delivery can be roughly divided into two categories: drug delivery based on microneedles (MNs) and drug delivery based on micro-reservoirs [17,48,49,50]

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Summary

Introduction

Many therapeutic drugs might face problems such as low biodistribution, limited solubility, poor absorption, and drug aggregation. With its unprecedented advantage in the precise control of fluid, it can improve the fabrication efficiency and quality of drug delivery, and shows great potential for the predictive power of preclinical drug carrier testing through biomimetic microfluidic platforms [4]. Several recent reviews have summarized microfluidic-based cell culture models to engineer micro-sized human tissues and organs These models can help accelerate drug development by resolving the discrepancies in animal models in certain aspects. We first highlight the application of microfluidics technology in the establishment of a variety of emerging DDSs over the past five years, including the fabrication of nanoparticle-based systems and carrier-free systems, and summarize biomimetic in vitro models on microfluidic chips to assess DDSs. Overall, recent innovations and advances in microfluidic-based systems are expected to accelerate the transition of new DDSs to clinical evaluation

Synthesis of Drug Delivery Carriers on Microfluid Chips
Lipid-Based Nanoparticles
Polymeric Nanoparticles
Inorganic Nanoparticles
Microfluidic Chip for Carrier-Free Drug Delivery
MNs-Based System
Solid MNs
Coated MNs
Dissolving MNs
Hydrogel MNs
Hollow MNs
Micro-Reservoir System
Active Actuation Mode for Micro-Reservoir System
Passive Actuation Mode for Micro-Reservoir System
InAfter
Mucosal Diffusion Barrier Model
Vessel Model
Gut-on-a-Chip
Different
Conclusions and Prospective
Full Text
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