Abstract
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.
Highlights
The treatment of primer liver tumors is not sufficiently efficient because of the late recognition [1]
Atactic poly([R,S]-3-hydroxybutyrate) with a molecular weight 2200 g/mol was selected in preliminary tests as the most promising drug carrier, and it was optimized for sorafenib and doxorubicin co-encapsulation by emulsion–solvent evaporation method
Comparing the release of active agents according to the polymers, it can be seen that the doxorubicin initial burst is slightly higher in both of the media from PEGylated PHB than from PHB, while the tmax values are smaller for PEGylated PHB than for the PHB studied in the same medium (Table 2)
Summary
The treatment of primer liver tumors (hepatocellular carcinoma, HCC) is not sufficiently efficient because of the late recognition [1]. [17] Its copolymers/composites can be utilized in bone implants [18,19], during the last decade PHB-based nanoparticles have been considered as promising drug delivery systems. They are biodegradable and bioresorbable which means that they can be eliminated through natural pathways by filtration or metabolism. Atactic poly([R,S]-3-hydroxybutyrate) with a molecular weight 2200 g/mol was selected in preliminary tests as the most promising drug carrier, and it was optimized for sorafenib and doxorubicin co-encapsulation by emulsion–solvent evaporation method. Size, wdiesrpeearslsitoyparnodduycieedldtoaesxwteenldl aths etihrecierncucalaptsiounlahtiaolnf-leiffefi.cPieanrtciycleofmthorepahcotliovgeya, gsieznet,sdwispereerssittyudainedd.yTiehlde raeslewaeslel aksintehteicesnocfapdsuuallatdiorunge-ffiloacideendcyPoHfBthaenadctPivEeGayglaetnetds wPHerBe sntaundoiepda.rtTichleesrewleearseeaklsinoeetixctsenosfidvuelayl sdtruudgi-eldoa. ded PHB and PEGylated PHB nanoparticles were extensively studied
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