<b>Theranostic polymeric nanocarriers modified by enhanced gadolinium conjugation techniques</b>

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

doi:10.3762/bxiv.2019.1.v1

2019

DOI: 10.3762/bxiv.2019.1.v1

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Theranostic polymeric nanocarriers modified by enhanced gadolinium conjugation techniques

Tivadar Feczkó¹,

Albrecht Piiper²,

Thomas Pleli³

et al.

Abstract: Background: Efficient delivery of the poorly water-soluble compound sorafenib still poses a challenge to current formulation strategies. To incorporate the lipophilic molecule into biocompatible and biodegradable theranostic nanoparticles has great potential for improving efficacy and safety of cancer therapy. Results: In this study, sorafenib nanoencapsulation was optimized using poly(D,L-lactide-co-glycolide) and polyethylene glycol-poly(D,L-lactide-co-glycolide) copolymers comparing three different technol… Show more

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Cited by 6 publications

References 13 publications

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Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

et al. 2021

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The drug-loaded nanocarriers have overcome various challenges compared with the pure chemotherapeutic drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, and adverse drug reactions, offering advantages such as protection from degradation in the blood stream, better drug solubility, and improved drug stability. One promising group of controlled and targeted drug delivery systems is polymer-based nanoparticles that can sustain the release of the active agent by diffusion and their degradation. Sorafenib is the only drug that can prolong the life of patients suffering from hepatocellular carcinoma. Cisplatin remains one of the most widely used broad-spectrum anticancer drugs for the treatment of a variety of solid tumours. Nanoformulations can exert a synergistic effect by entrapping two drugs with different modes of action, such as sorafenib and cisplatin. In our study, polymeric nanoparticles were prepared with a good production yield by an improved double emulsion solvent evaporation method using the copolymer of 12-hydroxystearic acid with ε-caprolactone (12CL), a biocatalytically synthesised biocompatible and biodegradable carrier, for the co-entrapment of sorafenib and cisplatin in nanotherapeutics. A bovine serum albumin (BSA) model compound was used to increase the cisplatin incorporation; then, it was successfully substituted by a iRGD tumour penetrating peptide that might provide a targeting function of the nanoparticles.

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Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

et al. 2021

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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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Assessment of Efficacy and Safety Using PPAR-γ Agonist-Loaded Nanocarriers for Inflammatory Eye Diseases

Miralles

Kamma-Lorger

Doménech

et al. 2022

IJMS

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Drug-loaded nanocarriers (NCs) are new systems that can greatly improve the delivery and targeting of drugs to specific tissues and organs. In our work, a PPAR-γ agonist loaded into polymeric NCs was prepared, stabilized by spray-drying, and tested in vitro, ex vivo, and in vivo (animal models) to provide a safe formulation for optical anti-inflammatory treatments. The NCs were shown to be well tolerated, and no signs of irritancy or alterations of the eye properties were detected by the in vitro HET-CAM test and in vivo Draize test. Furthermore, no signs of cytotoxicity were found in the NC formulations on retinoblastoma cells (Y-79) analyzed using the alamarBlue assay, and the transmittance experiments evidenced good corneal transparency with the formulations tested. The ocular anti-inflammatory study confirmed the significant prevention efficacy using the NCs, and these systems did not affect the corneal tissue structure. Moreover, the animal corneal structure treated with the NCs was analyzed using X-ray diffraction using synchrotron light. Small-angle X-ray scattering (SAXS) analysis did not show a significant difference in corneal collagen interfibrillar spacing after the treatment with freshly prepared NCs or NCs after the drying process compared to the corresponding negative control when inflammation was induced. Considering these results, the PPAR-γ agonist NCs could be a safe and effective alternative for the treatment of inflammatory ocular processes.

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Theranostic polymeric nanocarriers modified by enhanced gadolinium conjugation techniques

Cited by 6 publications

References 13 publications

Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

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

Assessment of Efficacy and Safety Using PPAR-γ Agonist-Loaded Nanocarriers for Inflammatory Eye Diseases

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