A Review of Stimuli-Responsive Nano Carriers for Drug and Gene Delivery

Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, MA 02115, United States.
Journal of Controlled Release (Impact Factor: 7.71). 04/2008; 126(3):187-204. DOI: 10.1016/j.jconrel.2007.12.017
Source: PubMed


Nanotechnology has shown tremendous promise in target-specific delivery of drugs and genes in the body. Although passive and active targeted-drug delivery has addressed a number of important issues, additional properties that can be included in nanocarrier systems to enhance the bioavailability of drugs at the disease site, and especially upon cellular internalization, are very important. A nanocarrier system incorporated with stimuli-responsive property (e.g., pH, temperature, or redox potential), for instance, would be amenable to address some of the systemic and intracellular delivery barriers. In this review, we discuss the role of stimuli-responsive nanocarrier systems for drug and gene delivery. The advancement in material science has led to design of a variety of materials, which are used for development of nanocarrier systems that can respond to biological stimuli. Temperature, pH, and hypoxia are examples of "triggers" at the diseased site that could be exploited with stimuli-responsive nanocarriers. With greater understanding of the difference between normal and pathological tissues and cells and parallel developments in material design, there is a highly promising role of stimuli-responsive nanocarriers for drug and gene delivery in the future.

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    • "Development of remotely controlled drug release techniques for noninvasive and spatiotemporal administration has attracted increasing attentions these years [1] [2] [3]. To date, a variety of external stimuli have been employed, such as thermal, electric, magnetic, optical excitations and ultrasound [2] [4] [5]. Owing to its ease of administration, the highintensity-focused ultrasound (HIFU)-triggered drug delivery system is of particular interest for locally on-demand delivery of therapeutic agents, including proteins, peptides and small molecular drugs [6] [7] [8] [9]. "
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    ABSTRACT: Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, was introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against E. coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to surrounding tissue, such as thermal ablation. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 08/2015; DOI:10.1016/j.jconrel.2015.08.033 · 7.71 Impact Factor
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    • "Typically such a control is obtained by changing the environmental conditions (e.g. ultrasound, UV–vis light, temperature, or pH of the bulk medium) [1] [2] [3] [4] [5]. Among these, temperature controlled drug release has received special interest due to its noninvasive character [6]. "
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    ABSTRACT: High-transition temperature liposomes with embedded coated magnetite nanoparticles were prepared using the thin lipid film hydration method in order to obtain magnetoliposomes not sensitive to temperature increase (at least up to 50°C). Accordingly, drug can be released from such magnetoliposomes using a low-level electromagnetic field as triggering agent, while no delivery would be obtained with temperature increase within the physiological acceptable range. The hypothesized release mechanism involves mechanical stress of the liposome membrane due to nanoparticles oscillations and it is investigated by means of a numerical model evaluated using multiphysics simulations. The carrier content was repetitively released by switching on and off a 20kHz, 60A/m magnetic field. The results indicated high reproducibility of cycle-to-cycle release induced by the magnetic-impelled motions driving to the destabilization of the bilayer rather than the liposome phase transition or the destruction of the liposome structure. Copyright © 2015. Published by Elsevier B.V.
    Colloids and surfaces B: Biointerfaces 04/2015; 131. DOI:10.1016/j.colsurfb.2015.04.030 · 4.15 Impact Factor
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    • "Nanometer scaled particles prepared with natural or synthetic polymers, lipids, or inorganic solids have been widely investigated as therapeutic carriers for anti-cancer drugs [1]. These particles, once injected into the bloodstream, can passively accumulate in tumors due to the leaky tumor vasculature and reduced lymphatic drainage, a phenomenon called enhanced permeability and retention (EPR) effect [2]. "
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    ABSTRACT: Ultrasound induced microbubble cavitation can cause enhanced permeability across natural barriers of tumors such as vessel walls or cellular membranes, allowing for enhanced therapeutic delivery into the target tissues. While enhanced delivery of small (<1nm) molecules has been shown at acoustic pressures below 1MPa both in vitro and in vivo, the delivery efficiency of larger (>100nm) therapeutic carriers into cancer remains unclear and may require a higher pressure for sufficient delivery. Enhanced delivery of larger therapeutic carriers such as FDA approved pegylated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NP) has significant clinical value because these nanoparticles have been shown to protect encapsulated drugs from degradation in the blood circulation and allow for slow and prolonged release of encapsulated drugs at the target location. In this study, various acoustic parameters were investigated to facilitate the successful delivery of two nanocarriers, a fluorescent semiconducting polymer model drug nanoparticle as well as PLGA-PEG-NP into human colon cancer xenografts in mice. We first measured the cavitation dose produced by various acoustic parameters (pressure, pulse length, and pulse repetition frequency) and microbubble concentration in a tissue mimicking phantom. Next, in vivo studies were performed to evaluate the penetration depth of nanocarriers using various acoustic pressures, ranging between 1.7 and 6.9MPa. Finally, a therapeutic microRNA, miR-122, was loaded into PLGA-PEG-NP and the amount of delivered miR-122 was assessed using quantitative RT-PCR. Our results show that acoustic pressures had the strongest effect on cavitation. An increase of the pressure from 0.8 to 6.9MPa resulted in a nearly 50-fold increase in cavitation in phantom experiments. In vivo, as the pressures increased from 1.7 to 6.9MPa, the amount of nanoparticles deposited in cancer xenografts was increased from 4- to 14-fold, and the median penetration depth of extravasated nanoparticles was increased from 1.3-fold to 3-fold, compared to control conditions without ultrasound, as examined on 3D confocal microscopy. When delivering miR-122 loaded PLGA-PEG-NP using optimal acoustic settings with minimum tissue damage, miR-122 delivery into tumors with ultrasound and microbubbles was 7.9-fold higher compared to treatment without ultrasound. This study demonstrates that ultrasound induced microbubble cavitation can be a useful tool for delivery of therapeutic miR loaded nanocarriers into cancer in vivo. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 02/2015; 203. DOI:10.1016/j.jconrel.2015.02.018 · 7.71 Impact Factor
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