PhD, National University of Singapore
Millifluidic platform for synthesis of polymeric nanoparticles with tunable and uniform size
Polymeric nanoparticles have drawn significant attention in the area of fluorescent imaging and drug delivery due to their biocompatibility and unique physiochemical properties. Facile preparation of polymeric nanoparticles is achieved by encapsulating hydrophobic dye or drug with the biocompatible amphiphilic polymer through a technique called nanoprecipitation. Among all physiochemical properties, size and shape are the most important parameters of NPs for their wide application in nanomedicine . In this work, we report a novel platform for synthesis of nanoparticles with high production and high controllability in terms of size, shape and reproducibility. We have designed a new cross-mixing based millifluidic jet mixer for tight control over the nanoparticle size and shape by varying Reynolds number, water to solvent ratio (WSR) and polymer to dye ratio (PDR).
Abstract: Polymeric nanoparticles (NPs) are one of the most studied organic strategies for nanomedicine. Intense interest lies in the potential of polymeric NPs to revolutionize modern medicine. To determine the ideal nanosystem for more effective and distinctly targeted delivery of therapeutic applications, particle size, morphology, material choice, and processing techniques are all research areas of interest. Utilizations of polymeric NPs include drug delivery techniques such as conjugation and entrapment of drugs, prodrugs, stimuli-responsive systems, imaging modalities, and theranostics. Cancer, neurodegenerative disorders, and cardiovascular diseases are fields impacted by NP technologies that push scientific boundaries to the leading edge of transformative advances for nanomedicine. WIREs Nanomed Nanobiotechnol 2016, 8:271-299. doi: 10.1002/wnan.1364 For further resources related to this article, please visit the WIREs website.
Pub.: 01 Sep '15, Pinned: 22 Aug '17
Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.
Pub.: 12 Nov '16, Pinned: 22 Aug '17
Abstract: Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).
Pub.: 06 Mar '12, Pinned: 22 Aug '17
Abstract: Using the fluorescent probe dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a surrogate for hydrophobic drugs, we investigate the effects of water content and on-chip flow rate on the multiscale structure, loading and release properties of DiI-loaded poly(ε-caprolactone)-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles produced in a gas-liquid segmented microfluidic device. We find a linear increase in PCL crystallinity within the nanoparticle cores with increasing flow rate, while mean nanoparticle sizes first decrease and then increase with flow rate coincident with the disappearance and reappearance of long filament nanoparticles. Loading efficiencies at the lower water content (cwc+10wt%) are generally higher (up to 94%) compared to loading efficiencies (up to 53%) at the higher water content (cwc+75wt%). In vitro release times range between ∼2 and 4days for nanoparticles produced at cwc+10wt% and >15days for nanoparticles produced at cwc+75wt%. At the lower water content, slower release of DiI is found for nanoparticles produced at higher flow rate, while at high water content, release times first decrease and then increase with flow rate. Finally, we investigate the effects of the chemical and physical characteristics of the release medium on the kinetics of in vitro DiI release and nanoparticle degradation. This work demonstrates the general utility of dye-loaded nanoparticles as model systems for screening chemical and flow conditions for producing drug delivery formulations within microfluidic devices.
Pub.: 11 May '16, Pinned: 31 Jul '17
Abstract: A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties.
Pub.: 17 Apr '14, Pinned: 31 Jul '17
Abstract: A versatile and robust microfluidic nanoprecipitation platform for high throughput synthesis of nanoparticles is fabricated. The versatility of this platform is proven through the successful preparation of different types of nanoparticles. This platform presents great robustness, with homogeneous nanoparticles always being obtained, regardless of the formulation parameters. The diameter and surface charge of the prepared nanoparticles can also be easily tuned.
Pub.: 17 Feb '15, Pinned: 31 Jul '17
Abstract: An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.
Pub.: 25 Apr '12, Pinned: 31 Jul '17