On‐Chip Fabrication of Paclitaxel‐Loaded Chitosan Nanoparticles for Cancer Therapeutics

Majedi, Fatemeh Sadat; Hasani-Sadrabadi, Mohammad Mahdi; VanDersarl, Jules J.; Mokarram, Nassir; Hojjati-Emami, Shahirar; Dashtimoghadam, Erfan; Bonakdar, Shahin; Shokrgozar, Mohammad Ali; Bertsch, Arnaud; Renaud, Philippe

doi:10.1002/adfm.201301628

Cited by 114 publications

(79 citation statements)

References 39 publications

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“…Microfluidics is attractive for making chitosan nanoparticles. Although fast mixing in microfluidics remains a challenge due to its laminar flow characteristics (Rhee et al, 2011), it has been demonstrated computationally (Kamat et al, 2015) and experimentally (Cetin et al, 2014;Chen et al, 2014b;Majedi et al, 2014) that introducing active mixers can facilitate rapid mixing through chaotic advection and diffusion. Cetin et al designed a microfluidic device (Fig.…”

Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

“…For example, chitosan/cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN) NPs prepared using a microfluidic method exhibited enhanced cellular uptake and immunostimulatory response in comparison to the NPs synthesized via the conventional bulk mixing method (Chen et al, 2014b). (Majedi et al, 2014).…”

Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

“…Majedi et al made a T-shaped microfluidic device with a hydrodynamically focused flow that had well-controlled mixing regime to synthesize monodispersed chitosan NPs (Fig. 4B) (Majedi et al, 2014). The physical (e.g., size and zeta potential) and chemical (e.g., biocompatibility) properties of the chitosan NPs can be tuned by controlling the mixing 19 time and by using controlled pH-changes in water to drive the assembly of NPs, respectively.…”

Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

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Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Ran

Sun

Baby

et al. 2017

Chemical Engineering Science

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Multiphase microfluidics has attracted significant interest in making micro-and nanostructures for various applications because of its capabilities in precisely controlling and manipulating a small volume of liquids. In this review, we introduce the recent advances in making micro-and nanostructures for pharmaceutical applications, including microparticles and microcapsules for controlled release, nanoparticles for drug delivery and microgels for 3D cell culture. With the development of more advanced microfluidic systems, the research focus in this field has shifted from making simple micro-and nanostructures to multifunctional systems to achieve more desirable functions. However, these multifunctions may lose their advantages that have been demonstrated in vitro once they are applied in vivo or later in human. The key challenge is a lack of fundamental understanding of the interactions between the micro-and nanomaterials and the biology systems. Consequently, the translation of these advanced materials lags far behind their extensive laboratory research.To better understand the micro-or nano-bio interactions, the development of new in vivomimicking models is imperative. Microfluidics has demonstrated its great potential in creating physiologically relevant models including 3D cell culture, tumor-on-a-chip and organs-on-a-chip. Therefore, efforts towards developing 3D cell culture and biomimetic chips including tumor-on-a-chip and organs-on-chips for faster and reliable evaluation of these micro-and nanosystems are also highlighted.

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Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

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Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Ran

Sun

Baby

et al. 2017

Chemical Engineering Science

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“…pH-sensitive polymers are polyelectrolytes whose coiled chains expand upon ionization, in response to changes in environmental pH, and their hydrodynamic volume increases dramatically due to electrostatic repulsion from the charges generated (anions or cations) along the backbone (Figure 2) (Qiu & Park, 2001;Majedi et al, 2013). Two main strategies exist in the design of pH-sensitive drug delivery systems: the use of polymeric systems with ionizable groups attached to the backbone that their conformational or solubility properties changes in response to changes in pH values and the use of polymers bearing acid-sensitive bonds whose cleavage triggers the release of drug molecules attached to the polymer backbone, modification of the polymer charge or the exposure of targeting ligands (n ¼ 4 independent experiments) (Majedi et al, 2013).…”

Section: Ph-sensitive Polymersmentioning

confidence: 99%

Classification of stimuli–responsive polymers as anticancer drug delivery systems

et al. 2014

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Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

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“…During the past two decades, a substantial amount of work has been published that this polymer is very suitable for preparation of nano-and microparticles for controlled drug release and offers valuable advantages as a drug delivery carrier for both small molecular drugs, like nicotine (Hui Wang, George, Bartlett, Gao, & Islam, 2017), paclitaxel (Majedi et al, 2014), and macromolecules, such as RNA (Ragelle et al, 2014), DNA (Gan, Wang, Cochrane, & McCarron, 2005). A wide range of drug formulations including gels, capsules, tablets, inhalations have been manufactured by CS.…”

Section: Chitosan Nanoparticles As a Pulmonary Delivery Systemmentioning

confidence: 99%

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

Wang¹

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Cigarette smoking has become one of the leading causes of preventable deaths all over the world, causing a serious threat to human wellbeing and a tremendous economic burden to governments. The currently available treatment options for smoking cessation are not efficient. The pulmonary delivery of drugs by methods such as dry powder inhaler (DPI) has been recognized as one of the most efficient routes of drug delivery to the targeted area. The lung delivery of nicotine in this way would be expected to mimic the effects of tobacco smoking and could significantly reduce the negative health effects of smoking that result from nicotine addiction.The aim of this study is to develop nanoparticles with controlled physicochemical properties using biodegradable polymer of chitosan (CS) loaded with nicotine salt for pulmonary delivery as DPI formulations. The outcomes of this project are expected to be a safe and effective CS-based nicotine formulation for pulmonary delivery to treat nicotine dependence. This thesis specially addresses the research questions: (1) how to develop a feasible process to manufacture the nanoparticles suitable for pulmonary drug delivery using biodegradable polymer of CS containing nicotine salt; (2) how to develop an animal model for pulmonary drug delivery from DPI formulation using a nose-only inhalation device.The current therapeutic options for treatment of smoking addiction have been reviewed, and current advancements of technology in pulmonary drug delivery are summarised. Buccal administration of drugs exhibits a low oral bioavailability, and sublingual tablets and chewing gums can be swallowed before being absorbed.Although nasal spray of nicotine is a fast way to deliver nicotine into the bloodstream, Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery iii the rate of absorption is still not as rapid as cigarette smoking. Therefore, it is proposed that delivery of nicotine with sustained drug release profile direct into the deep lung is likely to more effectively mimic the rapid effects of cigarette smoking on a physiological level, which could eliminate patient craving and allow the tapering of nicotine level over time to improve patients' compliance.Water in oil (w/o) emulsion crosslinking method has been used to fabricate nicotine hydrogen tartrate (NHT)-loaded CS nanoparticles which separate as solid microaggregates. The physicochemical properties of particles are characterized by a series of techniques. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) shows that the prepared particles are spherical in morphology with rough surface after loading CS particles with NHT. Dynamic Light Scattering (DLS)by Zetasizer determined nanoparticle size ranging from 167.6 nm to 411 nm, while DLS by Mastersizer demonstrated that the microaggregates of these nanoparticles are in the respirable range (<5µm). The surface positive charge as measured by zeta potential tends to decrease with increase of mass ratios of NHT to CS, which is in contr...

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On‐Chip Fabrication of Paclitaxel‐Loaded Chitosan Nanoparticles for Cancer Therapeutics

Cited by 114 publications

References 39 publications

Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Classification of stimuli–responsive polymers as anticancer drug delivery systems

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

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