Polyhydroxyalkanoates, a family of natural polymers, and their applications in drug delivery

Abstract

Polyhydroxyalkanoates (PHAs) are natural biopolymers produced by various microorganisms as a reserve of carbon and energy. PHA synthesis generally occurs during fermentation under nutrient limiting conditions with excess carbon. There are two main types of PHAs, short chain length PHAs (scl-PHAs) and medium chain length PHAs (mcl-PHAs). The mechanical and thermal properties of PHAs depend mainly on the number of carbons in the monomer unit and its molecular weight. PHAs are promising materials for biomedical applications because they are biodegradable, non-toxic and biocompatible. The large range of PHAs, along with their varying physical properties and high biocompatibility, make them highly attractive biomaterials for use in drug delivery. They can be used to produce tablets, micro-and nanoparticles as well as drug eluting scaffolds. A large range of different PHAs have been explored and the results obtained suggest that PHAs are excellent candidates for controlled and targeted drug delivery systems.

Antibacterial PHAs coating for titanium implants

“…For instance, they can provide localized, site-specific drug delivery, which is especially important in applications such as cardiology and oncology, where targeted delivery can improve the effectiveness of treatment and minimize side effects or damage to healthy tissue [2]. The design of DDS highly relies on polymers, which is driven by the suitability of physicochemical, mechanical and processability of the polymer-based formulations [3].…”

“…Furthermore, the by-products of their hydrolytic degradation make it possible to obtain common blood constituents (a ketone body produced by the liver from fatty acids, ketogenesis) [8]. Pas have performed well in a number drug delivery applications due to their excellent biocompatibility, non-toxicity and biodegradability [3,9,10,11,12,13]. Metal-based drug eluting systems have received little attention in the literature in comparison to polymer-based systems.…”

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

“…Indeed, the choice of the hydrophobic block strongly impacts the physico-chemical properties of the resulting self-assembled systems such as the hydrodynamic radius and the critical micelle concentration (CMC) which are two key parameters. 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).…”

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

“…Most self-assembled systems using PHB are based on bacterial semi-crystalline poly((R)-3-hydroxybutyrate) P(R)-HB [43,[45][46][47][48][49][50][51][52][53][54][55][56][57]. Indeed, industrial production of bacterial PHB, and generally of PHAs (poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-4HB)), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHH), etc.…”

“…Furthermore, polyester nanoparticulate DDSs can be formed from either naturally occurring polymers such as chitosan [41] or PHAs [42][43][44], or from synthetic macromolecules such as PLA, PEG, PCL or PHAs. Indeed, PHAs can be advantageously both naturally (microbial PHAs) or synthetically (chemically) produced [43,[45][46][47][48][49][50][51][52][53][54][55][56][57]. Among the numerous PHAs, the ubiquitous biocompatible and biodegradable poly(3-hydroxybutyrate) (PHB) can be obtained from bacteria as isotactic PHB, while ROP of substituted -lactones provides a valuable entry into PHBs featuring various tunable microstructures (atactic, syndiotactic, isotactic) [58][59][60].…”