Enhancement of Drug Delivery in Tumors by Using Interaction of Nanoparticles with Ultrasound Radiation

Larina, Irina V.; Evers, B. Mark; Ashitkov, Taras V.; Bartels, C.; Larin, Kirill V.; Esenaliev, Rinat O.

doi:10.1177/153303460500400211

Cited by 85 publications

(69 citation statements)

References 28 publications

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“…[9][10][11][12] Subcutaneous or intravenous injection of the drug results in systemic chemotherapy side effects, and a sustained drug delivery system at the tumor site can enhance the antitumor effects of the drug. 13,14 Research has confirmed these results in animals. 13,14 5-FU has been developed into different delivery systems, including biodegradable microspheres, spraycoated with Eudragit ® S100 (Rohm GmbH & Co., KG, Kirschenallee D-64293 Darmstadt, Germany), 20 and poly(butylcyanoacrylate) nanoparticles for topical delivery of 5-FU.…”

Section: Introductionsupporting

confidence: 75%

“…13,14 Research has confirmed these results in animals. 13,14 5-FU has been developed into different delivery systems, including biodegradable microspheres, spraycoated with Eudragit ® S100 (Rohm GmbH & Co., KG, Kirschenallee D-64293 Darmstadt, Germany), 20 and poly(butylcyanoacrylate) nanoparticles for topical delivery of 5-FU. [21][22][23][24][25][26][27][28][29] However, for Phase I cancer patients surgical tumor resections with chemotherapy is still the main treatment method.…”

Section: Introductionsupporting

confidence: 75%

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Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors

Sun¹,

Chen²,

Yuan³

2013

IJN

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Background: Surgical tumor resection is the main treatment for tumors however the treatment process often results in massive bleeding and tumor cell residue. The main aim of this research was to address problems such as bleeding, systemic chemotherapy side effects while enhancing quality of life, and increasing drug concentrations at the tumor site by developing a novel formulation with local long-term efficacy for treatment of tumors and to stop bleeding. Methods: 5-Fluorouracil (5-FU) was suspended in an ethyl acetate solution of poly D,Llactide-co-glycolic acid (PLGA) and a vacuum drying method was applied. The hemostatic gelatin sponge loaded with 5-FU was prepared by absorption of the suspension. The in vitro and in vivo characteristics of the hemostatic gelatin sponge loaded with 5-FU (5-FU-HAGS) were investigated. Results: 5-FU-HAGS (hemostatic absorbable gelatin sponge loaded with 5-fluorouracil) was successfully produced with controlled release of the content and was reproducibly suitable for local tumor treatment as an implant to stop bleeding. The encapsulation efficiency of 5-FU-HAGS was above 98%. The in vitro 5-FU release kinetic profile matched a near zero-order equation for 20 days. The in vivo 5-FU plasma concentration was at a more stable level than when 5-FU solution was administered by subcutaneous injection. Bleeding can be stopped more effectively by coating a piece of blank gelatin sponge. The survival ratio of tumor-bearing mice using a 5-FU-HAGS subcutaneous implant was higher when compared to mice given a subcutaneous injection of 5-FU solution. Conclusion:The 5-FU-HAGS system is a potential and effective way of enhancing the survival ratio and improving the quality of life of tumor-bearing mice.

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Section: Introductionsupporting

confidence: 75%

Section: Introductionsupporting

confidence: 75%

Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors

Sun¹,

Chen²,

Yuan³

2013

IJN

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“…In particular, PS particles are considered to be inert and have low toxicity. They have the are capable of chemical modification and thus are well applied to cosmetics, sunscreen, and even to drug delivery (26). On the other hand, several in vivo analyses have suggested that pulmonary exposure to PS nanoparticles enhances lung inflammation (16)(17).…”

Section: Discussionmentioning

confidence: 99%

Size Effects of Polystyrene Nanoparticles on Atopic Dermatitis-like Skin Lesions in NC/NGA Mice

Yanagisawa

Takano

Inoue

et al. 2010

Int J Immunopathol Pharmacol

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Nano-sized particles are diffusing in the environment with the development of nanotechnology. Polystyrene (PS) nanoparticles are modified industrial products and pharmaceutical agents, however, adverse effects of PS nanoparticles remain to be elucidated. In the present study, we investigated the effects of PS nanoparticles with different sizes on the atopic dermatitis (AD)-like skin lesions in NC/Nga mice assumed to show the skin barrier defect/dysfunction in the presence or absence of mite allergen. Male NC/Nga mice were injected intradermally with three different-sized PS nanoparticles (25, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the local protein expression of inflammatory molecules in the ear and Ig production in serum. PS nanoparticles aggravated AD-like skin lesions related to mite allergen, which was paralleled by the local protein levels of interleukin-4, CCL2/monocyte chemotactic protein-I, CCL3/macrophage inflammatory protein-l alpha, and CCL4/macrophage inflammatory protein-l beta. In contrast, PS nanoparticles decreased interferon-y expression. Furthermore, exposure to PS nanoparticles induced ear swelling and CC-chemokine expression in the absence of allergen. These effects were greater with the smaller PS nanoparticles than with the larger ones regarding overall trend. These results suggest that exposure to PS nanoparticles under skin barrier defect/dysfunction can exacerbate AD-like skin lesions related to mite allergen in a size-dependent manner. The enhancing effects may be accounted for by T helper 2-biased immune responses. Furthermore, PS nanoparticles can evoke skin inflammation via the overexpression of CC-chemokines even in the absence of allergen in atopic subjects.Atopic dermatitis (AD) is a pruritic inflammatory skin disease and its prevalence has been increasing progressively in industrialized countries (1-2). The underlying immunological milieu of human atopic dermatitis (AD) is characterized by up-regulation of inflammatory cytokines, IgE overproduction in serum and the accumulation of inflammatory cells. In most cases, various factors including immunological abnormalities, skin barrier dysfunction, exposure to allergen such as mite, environmental toxicants and psychotic factors (3-4) can contribute to the initiation and/or progression of AD. In fact, many animal studies have shown that environmental toxicants including chemicals can be closely related to the increasing prevalence of allergic diseases including AD. Recently, we have reported that systemic exposure to di-(2-ethylhexyl) phthalate (DEHP), a typical environmental chemical as the most

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“…Ultrasound has been used in various drug delivery applications to enhance the release of pharmaceuticals in target tissues (Mitragotri 2005). The main mechanism for increased release is thought to be related to acoustic cavitation, which is the formation and/or activity of gas-or vapour-filled bubbles in the medium exposed to ultrasound (Larina et al 2005). Such bubbles can collapse violently and disrupt the structure of the particles, because of the very high shear stresses in the region of the collapse, the shock wave produced by the collapse and/or the emission of a high-speed liquid jet from the bubble towards the particle surface (Nyborg 2001).…”

Section: In Vitro Releasementioning

confidence: 99%

One-step electrohydrodynamic production of drug-loaded micro- and nanoparticles

Enayati

Ahmad

Stride

et al. 2009

J. R. Soc. Interface.

100

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The objective of this work was to produce drug-loaded nanometre-and micrometre-scale particles using a single-step process that provides control over particle size and size distribution. Co-axial electrohydrodynamic processing was used, at ambient temperature and pressure, with poly(lactic-co-glycolic acid) as the polymeric coating material and oestradiol as the encapsulated drug. The particle diameter was varied from less than 120 nm to a few micrometres, by simple methodical adjustments in the processing parameters ( polymer concentration and applied voltage). In vitro studies were performed to determine the drug release profile from the particles during unassisted and ultrasound-stimulated degradation in simulated body fluid. An encapsulation efficiency of approximately 70% was achieved and release of the drug was sustained for a period of over 20 days. Exposing the particles to ultrasound (22.5 kHz) increased the rate of release by approximately 8 per cent. This processing method offers several advantages over conventional emulsification techniques for the preparation of drug-loaded particles. Most significantly, process efficiency and the drug's functionality are preserved, as complex multistep processing involving harsh solvents, other additives and elevated temperatures or pressures are avoided. Production rates of 10 12 particles min 21 can be achieved with a single pair of co-axial needles and the process is amenable to being scaled up by using multiple sets.

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Enhancement of Drug Delivery in Tumors by Using Interaction of Nanoparticles with Ultrasound Radiation

Cited by 85 publications

References 28 publications

Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors

Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors

Size Effects of Polystyrene Nanoparticles on Atopic Dermatitis-like Skin Lesions in NC/NGA Mice

One-step electrohydrodynamic production of drug-loaded micro- and nanoparticles

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