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

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.

Development of a PHBV nanoparticle as a peptide vehicle for NOD1 activation

“…We could observe that our NPs behave as a triphasic type kinetic release profile, beginning with an erosion and rapid initial release of the agonist attached to the surface of the NPs, then the slow degradation of the polymer through the diffusion of water in the polymeric matrix and finally a sustained exchange over time (Soppimath et al, 2001 ; Hu et al, 2015 ). The peptide's full release occurs after 8 h under in vitro conditions; these values are comparable to those previously obtained by Babos et al ( 2020 ) and Pavot et al ( 2013 ). However, these values are contrasted by Silva et al ( 2015 ), with different immunostimulant agents encapsulated in NPs, by presenting a slow cumulative release around 15 days.…”

In vivo and Post-synthesis Strategies to Enhance the Properties of PHB-Based Materials: A Review

“…In addition, PHB is biocompatible, and its degradation inside the body occurs slowly. For this reason, PHB can be used both as a polymer drug carrier in case of gradual and controlled releasing kinetics and as scaffold in the field of tissue engineering (Degli Esposti et al, 2019 ; Babos et al, 2020 ). Anyway, despite the comparable features with synthetic polymers, PHB exploitation is strongly limited due to its high stiffness, brittleness, and narrow processability window.…”

Composite P(3HB-3HV)-CS Spheres for Enhanced Antibiotic Efficiency

“…Emulsification/solvent evaporation represents an efficient, facile and versatile method to obtain biopolymer systems (particles, spheres, capsules) for unconventional pharmaceutical formulations [ 59 , 60 ]. This method is suitable to develop micro-/nano-carriers for various compounds, including inorganic nanostructures [ 61 , 62 ], antimicrobial agents [ 63 ], chemodrugs [ 64 , 65 ] and liposoluble drugs [ 66 , 67 ].…”