Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Docetaxel-loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Co-polymer Composition

Version 1 : Received: 29 September 2020 / Approved: 30 September 2020 / Online: 30 September 2020 (12:47:17 CEST)

A peer-reviewed article of this Preprint also exists.

Fisol, F.A.; Sonvico, F.; Colombo, P.; Amirul, A.-A.A.; Wahab, H.A.; Majid, M.I.A. Docetaxel-Loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Copolymer Composition. Nanomaterials 2020, 10, 2123. Fisol, F.A.; Sonvico, F.; Colombo, P.; Amirul, A.-A.A.; Wahab, H.A.; Majid, M.I.A. Docetaxel-Loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Copolymer Composition. Nanomaterials 2020, 10, 2123.

Journal reference: Nanomaterials 2020, 10, 2123
DOI: 10.3390/nano10112123

Abstract

Polyhydroxyalkanoate (PHA) co-polymers show relatively higher in vivo degradation rate compared to other PHAs thus they received a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water soluble anticancer drug docetaxel (DCX) were produced using poly 3-hydroxybutyrate-co-4-hydroxybutyrate, P(3HB-co-4HB), co-polymers biosynthesised from Cupriavidus sp. USMAA1020 isolated from Malaysian environment. Three co-polymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Pre-formulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in term of average particles sizes around 150 nm and narrow particle size distribution (PDI below 0.100). The encapsulation efficiencies result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX; DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticles system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug to polymer ratio while for the 30% and 40% drug to polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.

Subject Areas

Biodegradable polymers; Nanoparticles; Cancer chemotherapy; Controlled release; Drug delivery systems

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