Doxorubicin-loaded PLGA nanoparticles for the chemotherapy of glioblastoma: Towards the pharmaceutical development

Maksimenko, Olga; Malinovskaya, Julia; Shipulo, E. V.; Osipova, Nadezhda; Razzhivina, V.A.; Arantseva, Diana; Yarovaya, O. V.; Mostovaya, U. L.; Khalansky, A. S.; Федосеева, В В; Алексеева, А. Ю.; Ванчугова, Л. В.; Gorshkova, M. Yu.; Kovalenko, Elena I.; Balabanyan, Vadim; Melnikov, Pavel; Baklaushev, Vladimir P.; Чехонин, В. П.; Kreuter, Jörg; Gelperina, Svetlana

doi:10.1016/j.ijpharm.2019.118733

Cited by 88 publications

(69 citation statements)

References 64 publications

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“…Nanoparticles made up of these polymers have been developed for the delivery of various hydrophilic and hydrophobic anticancer agents such as doxorubicin, 5-fluorouracil, cisplatin, paclitaxel, and docetaxel (Rafiei and Haddadi, 2017;Ashour et al, 2019;Domínguez-Ríos et al, 2019;Maksimenko et al, 2019;Mittal et al, 2019).…”

Section: Synthetic Biopolymersmentioning

confidence: 99%

Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors

et al. 2021

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Advances in nanotechnology have favored the development of novel colloidal formulations able to modulate the pharmacological and biopharmaceutical properties of drugs. The peculiar physico-chemical and technological properties of nanomaterial-based therapeutics have allowed for several successful applications in the treatment of cancer. The size, shape, charge and patterning of nanoscale therapeutic molecules are parameters that need to be investigated and modulated in order to promote and optimize cell and tissue interaction. In this review, the use of polymeric nanoparticles as drug delivery systems of anticancer compounds, their physico-chemical properties and their ability to be efficiently localized in specific tumor tissues have been described. The nanoencapsulation of antitumor active compounds in polymeric systems is a promising approach to improve the efficacy of various tumor treatments.

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Section: Synthetic Biopolymersmentioning

confidence: 99%

Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors

et al. 2021

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“…improved DOX loading into PLGA-based NPs, including use of emulsification or modified nanoprecipitation formulation method, hydrophobization of DOX or its conjugation to the polymer chains [76][77][78].…”

Section: Plos Onementioning

confidence: 99%

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

et al. 2021

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Amphiphilic block co-polymer nanoparticles are interesting candidates for drug delivery as a result of their unique properties such as the size, modularity, biocompatibility and drug loading capacity. They can be rapidly formulated in a nanoprecipitation process based on self-assembly, resulting in kinetically locked nanostructures. The control over this step allows us to obtain nanoparticles with tailor-made properties without modification of the co-polymer building blocks. Furthermore, a reproducible and controlled formulation supports better predictability of a batch effectiveness in preclinical tests. Herein, we compared the formulation of PLGA-PEG nanoparticles using the typical manual bulk mixing and a microfluidic chip-assisted nanoprecipitation. The particle size tunability and controllability in a hydrodynamic flow focusing device was demonstrated to be greater than in the manual dropwise addition method. We also analyzed particle size and encapsulation of fluorescent compounds, using the common bulk analysis and advanced microscopy techniques: Transmission Electron Microscopy and Total Internal Reflection Microscopy, to reveal the heterogeneities occurred in the formulated nanoparticles. Finally, we performed in vitro evaluation of obtained NPs using MCF-7 cell line. Our results show how the microfluidic formulation improves the fine control over the resulting nanoparticles, without compromising any appealing property of PLGA nanoparticle. The combination of microfluidic formulation with advanced analysis methods, looking at the single particle level, can improve the understanding of the NP properties, heterogeneities and performance.

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“…This reduces to overall incubation time [38]. As presented previously, doxorubicin-loaded PLGA nanoparticles do not induce hemolysis for at least 3 h of incubation with whole human blood [28]. An illustration of the assay is presented in Figure 4.…”

Section: Interaction Of Doxorubicin and Nanoparticles With Red Blood mentioning

confidence: 59%

“…At lowered pH values, protonation of the amino group lowers the affinity for the hydrophobic PLGA matrix [27]. Accordingly, the nanoparticle species prepared at different pH values are characterized by different drug load, encapsulation efficiency (Table 1), and release behavior [28].…”

Section: Physicochemical Characterization Of Nanoparticlesmentioning

confidence: 99%

Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

et al. 2021

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Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.

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Doxorubicin-loaded PLGA nanoparticles for the chemotherapy of glioblastoma: Towards the pharmaceutical development

Cited by 88 publications

References 64 publications

Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors

Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

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