Theranostic Sorafenib-Loaded Polymeric Nanocarriers Manufactured by Enhanced Gadolinium Conjugation Techniques

Feczkó, Tivadar; Piiper, Albrecht; Pleli, Thomas; Schmithals, Christian; Denk, Dominic; Hehlgans, Stephanie; Rödel, Franz; Vogl, Thomas J.; Wacker, Matthias G.

doi:10.3390/pharmaceutics11100489

Cited by 20 publications

(11 citation statements)

References 22 publications

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“…They can also control the drug release and contain active targeting moieties besides passive enhanced permeability and retention effect. Currently, drug-loaded nanoparticles are usually prepared using polylactide [ 8 ], poly(lactic- co -glycolic acid) (PLGA) [ 9 ] and poly(-caprolactone) [ 10 ] or their copolymers especially with poly(ethylene glycol) (PEG) [ 11 , 12 ]. PEGylation of the particles is a promising method to increase the lifetime of the nanoparticles in the blood stream [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery

Babos

Rydz

Kawalec

et al. 2020

IJMS

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Dual drug-loaded nanotherapeutics can play an important role against the drug resistance and side effects of the single drugs. Doxorubicin and sorafenib were efficiently co-encapsulated by tailor-made poly([R,S]-3-hydroxybutyrate) (PHB) using an emulsion–solvent evaporation method. Subsequent poly(ethylene glycol) (PEG) conjugation onto nanoparticles was applied to make the nanocarriers stealth and to improve their drug release characteristics. Monodisperse PHB–sorafenib–doxorubicin nanoparticles had an average size of 199.3 nm, which was increased to 250.5 nm after PEGylation. The nanoparticle yield and encapsulation efficiencies of drugs decreased slightly in consequence of PEG conjugation. The drug release of the doxorubicin was beneficial, since it was liberated faster in a tumor-specific acidic environment than in blood plasma. The PEG attachment decelerated the release of both the doxorubicin and the sorafenib, however, the release of the latter drug remained still significantly faster with increased initial burst compared to doxorubicin. Nevertheless, the PEG–PHB copolymer showed more beneficial drug release kinetics in vitro in comparison with our recently developed PEGylated poly(lactic-co-glycolic acid) nanoparticles loaded with the same drugs.

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Section: Introductionmentioning

confidence: 99%

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery

Babos

Rydz

Kawalec

et al. 2020

IJMS

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“…These differences were expected to be less pronounced in the in vivo situation due to the elimination of doxorubicin from the body. The three-dimensional pore structure is a well-known feature of PLGA nanoparticles [ 33 ]. Therefore, the adsorption of drug molecules to the particle surface was expected to have a strong influence on the release behavior.…”

Section: Resultsmentioning

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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“…Compared with free SOR, the SOR-NPs were more effective at inhibiting HepG2 cell growth in vitro and in vivo . Feczko et al loaded SOR into biocompatible and biodegradable thermally sensitive PLGA or PEG-PLGA NPs using an emulsion method and modified the surface with Gd-DTPA 194 . Compared with other particle systems described in the literature, these NPs exhibited better performance.…”

Section: Multifunctional Sor Nanoplatformsmentioning

confidence: 99%

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and angiogenesis and induces cancer cell apoptosis. It also improves the survival rates of patients with advanced liver cancer. However, due to its poor solubility, fast metabolism, and low bioavailability, clinical applications of sorafenib have been substantially restricted. In recent years, various studies have been conducted on the use of nanoparticles to improve drug targeting and therapeutic efficacy in HCC. Moreover, nanoparticles have been extensively explored to improve the therapeutic efficacy of sorafenib, and a variety of nanoparticles, such as polymer, lipid, silica, and metal nanoparticles, have been developed for treating liver cancer. All these new technologies have improved the targeted treatment of HCC by sorafenib and promoted nanomedicines as treatments for HCC. This review provides an overview of hot topics in tumor nanoscience and the latest status of treatments for HCC. It further introduces the current research status of nanoparticle drug delivery systems for treatment of HCC with sorafenib.

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Theranostic Sorafenib-Loaded Polymeric Nanocarriers Manufactured by Enhanced Gadolinium Conjugation Techniques

Cited by 20 publications

References 22 publications

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery

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

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma

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