A method of drug delivery to tumors based on rapidly biodegradable drug-loaded containers

Parakhonskiy, Bogdan; Shilyagina, Natalia Yu.; Gusliakova, Оlga I.; Volovetskiy, Artur B.; Kostyuk, A. B.; Balalaeva, Irina V.; Klapshina, Larisa G.; Лермонтова, С. А.; Tolmachev, Vladimir; Orlova, Anna; Gorin, Dmitry A.; Sukhorukov, Gleb B.; Zvyagin, Andrei V.

doi:10.1016/j.apmt.2021.101199

Cited by 19 publications

(20 citation statements)

References 53 publications

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“…It may be useful to externally stimulate the release of the encapsulated drug [ 52 ] or to attract magnetically sensitive containers to the vessel walls [ 28 ] in order to make retention more effective. This moment may also be the most successful for the implementation of local photodynamic therapy [ 53 , 54 ] or magnetic hyperthermia [ 55 ]. This is due to the fact that at this moment, most of the drug dosage is localized in the vessels of the target kidney with the optimal selection of the injection volume.…”

Section: Resultsmentioning

confidence: 99%

Renal Artery Catheterization for Microcapsules’ Targeted Delivery to the Mouse Kidney

et al. 2022

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The problem of reducing the side effects associated with drug distribution throughout the body in the treatment of various kidney diseases can be solved by effective targeted drug delivery. The method described herein involves injection of a drug encapsulated in polyelectrolyte capsules to achieve prolonged local release and long-term capillary retention of several hours while these capsules are administered via the renal artery. The proposed method does not imply disruption (puncture) of the renal artery or aorta and is suitable for long-term chronic experiments on mice. In this study, we compared how capsule size and dosage affect the target kidney blood flow. It has been established that an increase in the diameter of microcapsules by 29% (from 3.1 to 4.0 μm) requires a decrease in their concentration by at least 50% with the same suspension volume. The photoacoustic method, along with laser speckle contrast imaging, was shown to be useful for monitoring blood flow and selecting a safe dose. Capsules contribute to a longer retention of a macromolecular substance in the target kidney compared to its free form due to mechanical retention in capillaries and slow impregnation into surrounding tissues during the first 1–3 h, which was shown by fluorescence tomography and microscopy. At the same time, the ability of capillaries to perform almost complete “self-cleaning” from capsular shells during the first 12 h leads to the preservation of organ tissues in a normal state. The proposed strategy, which combines endovascular surgery and the injection of polymer microcapsules containing the active substance, can be successfully used to treat a wide range of nephropathies.

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Section: Resultsmentioning

confidence: 99%

Renal Artery Catheterization for Microcapsules’ Targeted Delivery to the Mouse Kidney

et al. 2022

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“…Noticeably, incubation in an aqueous solution with normal pH will lead to the recrystallization process of the unstable vaterite or ACC particles to the thermodynamically stable calcite phase, and the concomitant decrease in porosity will facilitate drug release [ 63 , 77 , 85 ]. All these processes strongly depend on the pH of the medium, and the particles dissolve quicker in a solution with acidic pH, but the shell of the calcium hydroxide can format in alkalic pH, which inhibits the dissolution of CCPs [ 73 , 74 ]. The presence of other ions can affect the recrystallisation rate, resulting in the release of drugs [ 49 , 75 , 110 ].…”

Section: Caco 3 Carriersmentioning

confidence: 99%

“…The loading of the photosensitizers demonstrated that decreasing the pH from 7.4 to 6.8 could significantly accelerate the release content from 30% to 50% in 3 h ( Figure 5 e) [ 74 ]. Similar dynamic demonstrated by DOX, for example, a low release rate (40%) of DOX was detected after 15 h of incubation in the phosphate buffer saline (PBS) at pH = 7.4, followed by a release rate of approximately 80% within 20 h. Decreasing pH to 4.8 stimulated the initial burst-release of up to 40% of encapsulated DOX within 15 min following with release of 60% of DOX after incubating for 30 min.…”

Section: Caco 3 Carriersmentioning

confidence: 99%

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Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications

et al. 2022

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Because free therapeutic drug molecules often have adverse effects on normal tissues, deliver scanty drug concentrations and exhibit a potentially low efficacy at pathological sites, various drug carriers have been developed for preclinical and clinical trials. Their physicochemical and toxicological properties are the subject of extensive research. Inorganic calcium carbonate particles are promising candidates as drug delivery carriers owning to their hardness, porous internal structure, high surface area, distinctive pH-sensitivity, low degradability, etc, while soft organic alginate hydrogels are also widely used because of their special advantages such as a high hydration, bio-adhesiveness, and non-antigenicity. Here, we review these two distinct substances as well as hybrid structures encompassing both types of carriers. Methods of their synthesis, fundamental properties and mechanisms of formation, and their respective applications are described. Furthermore, we summarize and compare similarities versus differences taking into account unique advantages and disadvantages of these drug delivery carriers. Moreover, rational combination of both carrier types due to their performance complementarity (yin-&yang properties: in general, yin is referred to for definiteness as hard, and yang is broadly taken as soft) is proposed to be used in the so-called hybrid carriers endowing them with even more advanced properties envisioned to be attractive for designing new drug delivery systems.

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“…Over the past few decades, the rapid development of nanotechnology and protein engineering has led to the creation of new schemes of diagnostics and treatment of socially significant diseases, including cancer [ 1 , 2 , 3 , 4 ]. Nanostructures, possessing unique properties such as fluorescence or high drug encapsulation capacity, are considered to be the most effective platform for the creation of smart methods of personalized diagnostics and cancer therapy [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Photothermal Therapy with HER2-Targeted Silver Nanoparticles Leading to Cancer Remission

et al. 2022

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Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are promising tools for diagnostics and cancer treatment. Among widely used metal nanoparticles, silver nanoparticles (Ag NPs) possess the strongest light scattering and surface plasmon strength. However, the therapeutic potential of Ag NPs has until now been underestimated. Here we show targeted photothermal therapy of solid tumors with 35 nm HER2-targeted Ag NPs, which were produced by the green synthesis using an aqueous extract of Lavandula angustifolia Mill. Light irradiation tests demonstrated effective hyperthermic properties of these NPs, namely heating by 10 °С in 10 min. To mediate targeted cancer therapy, Ag NPs were conjugated to the scaffold polypeptide, affibody ZHER2:342, which recognizes a clinically relevant oncomarker HER2. The conjugation was mediated by the PEG linker to obtain Ag-PEG-HER2 nanoparticles. Flow cytometry tests showed that Ag-PEG-HER2 particles successfully bind to HER2-overexpressing cells with a specificity comparable to that of full-size anti-HER2 IgGs. A confocal microscopy study showed efficient internalization of Ag-PEG-HER2 into cells in less than 2 h of incubation. Cytotoxicity assays demonstrated effective cell death upon exposure to Ag-PEG-HER2 and irradiation, caused by the production of reactive oxygen species. Xenograft tumor therapy with Ag-PEG-HER2 particles in vivo resulted in full primary tumor regression and the prevention of metastatic spread. Thus, for the first time, we have shown that HER2-directed plasmonic Ag nanoparticles are effective sensitizers for targeted photothermal oncotherapy.

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A method of drug delivery to tumors based on rapidly biodegradable drug-loaded containers

Cited by 19 publications

References 53 publications

Renal Artery Catheterization for Microcapsules’ Targeted Delivery to the Mouse Kidney

Renal Artery Catheterization for Microcapsules’ Targeted Delivery to the Mouse Kidney

Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications

Photothermal Therapy with HER2-Targeted Silver Nanoparticles Leading to Cancer Remission

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