Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles

Chiesa, Enrica; Dorati, Rossella; Modena, Tiziana; Conti, Bice; Genta, Ida

doi:10.1016/j.ijpharm.2017.11.044

Cited by 78 publications

(60 citation statements)

References 55 publications

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“…Previous studies have demonstrated the formulation of polymeric nanoparticles using microfluidics to incorporate small drugs molecules (e.g. [10,11]) or different types or RNA (e.g. [12]).…”

Section: Introductionmentioning

confidence: 99%

Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

Roces

Christensen

Perrie

2020

Drug Deliv. and Transl. Res.

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In the formulation of nanoparticles, poly(lactic-co-glycolic acid) (PLGA) is commonly employed due to its Food and Drug Administration and European Medicines Agency approval for human use, its ability to encapsulate a variety of moieties, its biocompatibility and biodegradability and its ability to offer a range of controlled release profiles. Common methods for the production of PLGA particles often adopt harsh solvents, surfactants/stabilisers and in general are multi-step and time-consuming processes. This limits the translation of these drug delivery systems from bench to bedside. To address this, we have applied microfluidic processes to develop a scale-independent platform for the manufacture, purification and monitoring of nanoparticles. Thereby, the influence of various microfluidic parameters on the physicochemical characteristics of the empty and the proteinloaded PLGA particles was evaluated in combination with the copolymer employed (PLGA 85:15, 75:25 or 50:50) and the type of protein loaded. Using this rapid production process, emulsifying/stabilising agents (such as polyvinyl alcohol) are not required. We also incorporate in-line purification systems and at-line particle size monitoring. Our results demonstrate the microfluidic control parameters that can be adopted to control particle size and the impact of PLGA copolymer type on the characteristics of the produced particles. With these nanoparticles, protein encapsulation efficiency varies from 8 to 50% and is controlled by the copolymer of choice and the production parameters employed; higher flow rates, combined with medium flow rate ratios (3:1), should be adopted to promote higher protein loading (% wt/wt). In conclusion, herein, we outline the process controls for the fabrication of PLGA polymeric nanoparticles incorporating proteins in a rapid and scalable manufacturing process.

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Section: Introductionmentioning

confidence: 99%

Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

Roces

Christensen

Perrie

2020

Drug Deliv. and Transl. Res.

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show abstract

“…MDs offer a relatively simple and consistent way for overcoming some of these issues, for synthesizing nanoparticles of uniform size, with better releasing profiles, from different materials such as PLGA, PEG, polycaprolactone (PCL), chitosan, and copolymers . Increased attention has been given to PLGA‐based nanoparticles as nanocarriers of small drugs, peptides, proteins, DNA, or RNA .…”

Section: Biomedical Applications Of Microfluidic Fabricated Materialsmentioning

confidence: 99%

“…However, the lack of reproducible and easily scalable preparation of PLGA nanoparticles has hindered their clinical and commercial uptake . Chiesa et al prepared N ‐acetylcysteine‐loaded PLGA nanoparticles using a MD with staggered herringbone micromixing; N ‐acetylcysteine is a small molecule hydrophilic drug with rapid clearance and unfavorable biodistribution depending on the route of administration. After 60 min incubation, N ‐acetylcysteine is released from PLGA nanoparticles prepared using bulk mixing nanoprecipitation.…”

Section: Biomedical Applications Of Microfluidic Fabricated Materialsmentioning

confidence: 99%

“…a) Schematic of the staggered herringbone micromixer with sequential regions of asymmetric ridges for the synthesis of PLGA nanoparticles for drug delivery. In vitro N ‐acetylcysteine ( N ‐Ac) release profiles from N ‐Ac loaded PLGA nanoparticles . b) Schematic of the addition of bFGF or PBAE/DNA nanoparticle to a PEG precursor solution and subsequent microsphere formation in a droplet‐based MD.…”

Section: Biomedical Applications Of Microfluidic Fabricated Materialsmentioning

confidence: 99%

Section: Biomedical Applications Of Microfluidic Fabricated Materialsmentioning

confidence: 99%

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Microfluidic Devices in Fabricating Nano or Micromaterials for Biomedical Applications

Luo

Zhang

et al. 2019

Adv Materials Technologies

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Nano or microsized particles have been a research focus for decades, and the advancement of microfluidic technologies provides alternative strategies for the synthesis of such materials for various applications. Recent advances of using different microfluidic devices (MDs), including continuous laminar flow, segmented flow, droplet‐based, and other non‐chip‐based microreactors, for the synthesis of nano or microsized particles with specific properties are reviewed, along with their biomedical applications. Different categories of particles fabricated in MDs are summarized to highlight the wide application of the processing platform in the development of novel functional materials.

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A Comprehensive Review of One Decade of Microfluidic Platforms Applications in Synthesis of Enhanced Carriers Utilized in Controlled Drug Delivery

Siavashy,

Soltani,

Ahmadi

et al. 2022

Adv Materials Technologies

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Physical and chemical characteristics of NPs highly depend on their shapes, sizes, structures, morphologies, surface properties, and chemical compositions, [8,9] which are modifiable. In addition, NPs can carry small molecules, imaging agents, deoxyribonucleic acid (DNA), antibodies, peptides, proteins, or other substances to specific parts of the body. [10,11] On the other hand, investigations on different diseases have confirmed the need for a paradigm shift in the development of drugs and delivery systems. Hence, developing novel therapeutics and delivery approaches to treat diseases is a significant problem. [12] Therefore, many novel strategies based on innovative solutions have been developed. [13][14][15] Among these strategies, the synthesis of nanocarriers using microfluidic (MF) technology has become popular in recent years. This multidisciplinary technology is a unique platform for chemistry, medicine, pharmacy, physics, biology, materials science, fluid mechanics, and engineering. [16,17] Specifically, it has played a pivotal role in developing drug delivery systems. [18][19][20] Therefore, it is crucial to study MF experiments' practical potential and advantages over conventional methods. Furthermore, considering a high surface-to-volume ratio in MFs, they require fewer chemical reagents and generate less waste, making them suitable for Novel nanocarriers such as multifunctional nanoparticles (NPs) have recently attracted attention due to their various applications, specifically in medicine and treatment. However, it is vital that these particles be synthesized with meticulous control of different structural, chemical, and physical properties. In response to this demand, microfluidic (MF) technology as a reliable procedure can provide promising results in the development of desired NPs and efficient drug delivery systems. By controlling the flow rates of multiphase fluids and conditions of chemical reactions, MF technology enables the fabrication of uniform and highly stable particles with enhanced surfaces, higher encapsulation efficiency, and controlled release of therapeutic agents compared with conventional bulk methods. This review article investigates the MF-based methods utilized in the synthesis of NPs and their advantages in developing novel drug delivery systems. It also provides a comprehensive comparison with conventional methods from a different point of view, emphasizing a novel category of nanocarriers' critical characteristics. In addition, a summary of the most recent representative works on NPs fabrication by MF procedures is presented, and their potential and applications in drug delivery are discussed.The ORCID identification number(s) for the author(s) of this article can be found under

show abstract

Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles

Cited by 78 publications

References 55 publications

Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

Microfluidic Devices in Fabricating Nano or Micromaterials for Biomedical Applications

A Comprehensive Review of One Decade of Microfluidic Platforms Applications in Synthesis of Enhanced Carriers Utilized in Controlled Drug Delivery

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