Development and characterization of bio-derived polyhydroxyalkanoate nanoparticles as a delivery system for hydrophobic photodynamic therapy agents

Abstract

In this study, we developed and investigated nanoparticles of biologically-derived, biodegradable polyhydroxyalkanoates (PHAs) as carriers of a hydrophobic photosensitizer, 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H, 23H-porphine (pTHPP) for photodynamic therapy (PDT). Three PHA variants; polyhydroxybutyrate, poly(hydroxybutyrate-co-hydroxyvalerate) or P(HB-HV) with 12 and 50% HV were used to formulate pTHPP-loaded PHA nanoparticles by an emulsification-diffusion method, where we compared two different poly(vinyl alcohol) (PVA) stabilizers. The nanoparticles exhibited nano-scale spherical morphology under TEM and hydrodynamic diameters ranging from 169.0 to 211.2 nm with narrow size distribution. The amount of drug loaded and the drug entrapment efficiency were also investigated. The in vitro photocytotoxicity was evaluated using human colon adenocarcinoma cell line HT-29 and revealed time and concentration dependent cell death, consistent with a gradual release pattern of pTHPP over 24 h. This study is the first demonstration using bacterially derived P(HB-HV) copolymers for nanoparticle delivery of a hydrophobic photosensitizer drug and their potential application in PDT.

Recent Advances in Bioplastics: Application and Biodegradation

“…Doxorubicin loaded folate conjugated PEG-PHA nanoparticles showed a significant 3.5-fold in vivo regression of the tumour volume in BALB/c nude mice compared to doxorubicin addition in free-form. A different approach that utilised PHA-based DDS encapsulated a hydrophobic photosensitizer (pTHPP) for a photodynamic therapeutic potential against selected cancer cells line (HT-29 cells) after 24 h [94]. There appears to be a direct correlation between PHA molecular weight and the controlled release of the photosensitiser and maximum photocytotoxic effect with respect to NPs of different polymeric formulations.…”

“…Kim and co-workers [135] used a PLLA-based optical needle against skin cancer in a photodynamic therapeutic setting, achieving a 9-fold improvement in light delivery using this biodegradable device; additionally, blue-light delivery for antimicrobial effect was achieved. Pramual and colleagues [94] were the first to attempt the use of PHA nanoparticles as drug-carriers for photodynamic therapy (PDT). As both the PHA nanoparticle and the photosensitizer (pTHPP) are hydrophobic, it was quite easy to achieve a stable construct by mixing these two.…”

Opsonisation of nanoparticles prepared from poly(β-hydroxybutyrate) and poly(trimethylene carbonate)-b-poly(malic acid) amphiphilic diblock copolymers: Impact on the in vitro cell uptake by primary human macrophages and HepaRG hepatoma cells

“…Poly(hydroxyalkanoates) (PHAs) and poly(carbonates) (PCs) have attracted considerable attention for the design of drug delivery systems due to their high biocompatibility and low toxicity (Furrer et al, 2008;Wu et al, 2009;Hazer, 2010;Hu et al, 2012;Shrivastav et al, 2013;Chen et al, 2014;Loyer and Cammas-Marion, 2014;Li and Loh, 2015;Nigmatullin et al, 2015). In this context, poly(3-hydroxybutyrate) and poly(trimethylene carbonate) have been developed to produce gels and matrices for tissue engineering (Shishatskaya et al, 2004 ;Asran et al, 2010 ;Song et al, 2011 ;Schüller-Ravoo et al, 2013 ;Rozila et al, 2016 ;Ding et al, 2016 ;Pascu et al, 2016 ;Zant et al, 2016) and NPs for drug delivery (Xiong et al, 2010 ;Jiang et al, 2013 ;Fukushima 2016 ;Pramual et al, 2016). Our laboratories have recently synthesized and characterized novel poly(hydroxyalkanoate)-based 7 amphiphilic diblock copolymers, namely poly(-malic acid)-b-poly(3-hydroxybutyrate) (PMLA-b-PHB) (Barouti et al, 2015) and poly(-malic acid)-b-poly(trimethylene carbonate) (PMLA-b-PTMC) (Barouti et al, 2016a), hydrophobic PMLA Be -b-PHB-b-PMLA Be and amphiphilic PMLA-b-PHB-b-PMLA triblock copolymers (Barouti et al, 2016b) as well as linear and star-shaped thermogelling poly([R]-3-hydroxybutyrate) copolymers (Barouti et al, 2016c).…”

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“…This in turn elevates the difficulty for diffusion of the drug into the external water phase, which in turn leads to increase drug retention in the particle and a higher EE 28 . In other words, the presence of increasing PVA concentration might serve as a barrier to prevent the diffusion of the drug out of the polymeric shell, resulting in the gradual increase of EE when the PVA concentration is elevated 29 .…”