Polyhydroxyalkanoates - what are the uses? Current challenges and perspectives.

Over the past few decades, a considerable attention has been focused on the microbial polyhydroxyalkanoates (PHAs) owing to its multifaceted properties, i.e. biodegradability, biocompatibility, non-toxicity and thermo-plasticity. This article presents a critical review of the foregoing research, current trends and future perspectives on the value added applications of PHAs in the biomedical, environmental and industrial domains of life.

Preparation, characterization and evaluation of HPßCD-PTX/PHB nanoparticles for pH-responsive, cytotoxic and apoptotic properties.

Paclitaxel (PTX) is a potent anticancer drug. However, PTX exhibits extremely poor solubility in aqueous solution along with severe side effects. Therefore, in this study, an inclusion complex was prepared between PTX and hydroxypropyl-ß-cyclodextrin (HPßCD) by solvent evaporation to enhance the drug's solubility. The HPßCD-PTX inclusion complex was then encapsulated in poly-3-hydroxybutyrate (PHB) to fabricate drug-loaded nanoparticles (HPßCD-PTX/PHB NPs) by nanoprecipitation. The HPßCD-PTX/PHB NPs depicted a higher release of PTX at pH 5.5 thus demonstrating a pH-dependent release profile. The cytotoxic properties of HPßCD-PTX/PHB NPs were tested against MCF-7, MDA-MB-231 and SW-620 cell lines. The cytotoxic potential of HPßCD-PTX/PHB NPs was 2.59-fold improved in MCF-7 cells in comparison to free PTX. Additionally, the HPßCD-PTX/PHB NPs improved the antimitotic (1.68-fold) and apoptotic (8.45-fold) effects of PTX in MCF-7 cells in comparison to PTX alone. In summary, these pH-responsive nanoparticles could be prospective carriers for enhancing the cytotoxic properties of PTX for the treatment of breast cancer.

Synthesis of poly-(3-hydroxybutyrate-co-12 mol % 3-hydroxyvalerate) by Bacillus cereus FB11: its characterization and application as a drug carrier.

The synthesis of microbial polyhydroxyalkanoate is investigated in this work for it potential application as drug carrier for cancer therapy. The bacterial isolate Bacillus cereus FB11 has synthesized poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer under nutrient stress conditions using glucose as a sole carbon source. The FTIR spectrum of the purified copolymer showed the characteristic absorption bands at 1,719, 1,260 and 2,931 cm(-1) attributing to C=O, C-O stretching and C-H vibrations, respectively. The result of (1)H-NMR confirmed that it was composed of 88 mol % of 3-hydroxybutyrate and 12 mol % of 3-hydroxyvalerate monomeric subunits. The nanoparticles were fabricated from copolymer and used as a carrier for anticancer drug ellipticine. The in vitro drug release studies showed that % inhibition of A549 cancer cell line receiving ellipticine loaded poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles was two-fold higher in comparison to ellipticine alone. This drug delivery system offers exciting possibilities for cancer therapy by increasing the bioavailability of anti-neoplastic drug to the tumor site.

Preparation, characterization and evaluation of antibacterial properties of epirubicin loaded PHB and PHBV nanoparticles.

Poly-3-hydroxybutyrate (PHB) and poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) are considered as ideal drug carriers due to their non-toxic, biodegradable and biocompatible nature. In this study, the epirubicin (EPI) was used as a model drug. The blank (PHBo, PHBVo) and drug loaded (EPI-PHB-PEG, EPI-PHBV-PEG) nanoparticles were prepared by nanoprecipitation method. The average particle size, polydispersity index and zeta potential of blank and drug loaded nanoparticles were determined. While, the morphology of blank and drug loaded nanoparticles was evaluated by scanning electron microscopy. The drug loading efficiency of EPI-PHB-PEG nanoparticles was higher in comparison to EPI-PHBV-PEG nanoparticles. A sustained release of EPI was found over a period of 8 days at pH 4 from EPI-PHB-PEG and EPI-PHBV-PEG nanoparticles in comparison to faster drug release at pH 7. The assessment of antibacterial properties of the drug loaded nanoparticles showed significant antibacterial properties against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains as compared to an equivalent amount of free drug.

Characterization of physical and biodegradation properties of poly-3-hydroxybutyrate-co-3-hydroxyvalerate/sepiolite nanocomposites.

The pristine sepiolite was treated with the 3-aminopropyl triethoxy silane (APTES). The APTES grafted sepiolite (APTES-G-SP) was used to develop the poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV)/sepiolite nanocomposite films by the solution-casting method. Scanning electron micrographs showed that the APTES-G-SP fibers were well embedded in the polymer matrix. Fourier transform Infrared spectroscopy attributed the formation of covalent bonds between the APTES-G-SP and PHBV in the nanocomposite film. Thermal and water-barrier properties of the nanocomposite films were significantly improved. Biodegradation studies indicated the conversion of the crystalline structure of the nanocomposite films into the amorphous one as a result of the synergistic effect of the abiotic and biotic degradation processes. The results of this study provide sound evidence about the use of the biodegradable nanocomposite films with the better thermal and water barrier properties for the food packaging industry.

Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed.

Encapsulation of Ellipticine in poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) based nanoparticles and its in vitro application.

Biodegradable, biocompatible, renewable and non-toxic polyhydroxyalkanoates (PHAs) based nanoparticles are the novel nanotherapeutic tool which are used for the encapsulation of antineoplastic drugs for cancer therapy. In this study, poly-3-hydroxybutyrate-co-5 mol% 3-hydroxyvalerate (PHBV-S), poly-3-hydroxybutyrate-co-11 mol% 3-hydroxyvalerate (PHBV-11) and poly-3-hydroxybutyrate-co-15 mol% 3-hydroxyvalerate (PHBV-15) were used as a nanocarrier for encapsulation of Ellipticine (EPT). EPT is a model anticancer drug. Physicochemical characteristics such as particle size, its morphology and zeta potential of blank and EPT loaded PHBV-S, PHBV-11 and PHBV-15 nanoparticles were studied. In vitro cytotoxicity tests confirmed that the blank PHBV-S, PHBV-11 and PHBV-15 nanoparticles were demonstrating significant biocompatibility without affecting the survival of cancer cell line A549. The loading efficiency of EPT in PHBV nanoparticles was observed in the range of 39.32 to 45.65%. The % inhibition of cancer cell line A549 ranged from 64.28 to 67.77% in comparison to EPT alone in which % inhibition found to be ≤45.11%. The IC50 value for each of three different formulations of EPT loaded PHBV nanoparticles ranged from 1.00 to 1.31 µg/mL. The order of % inhibition of cancer cell line A549 for drug loaded nanoparticles was EPT-PHBV-15>EPT-PHBV-S>EPT-PHBV-11. This system had demonstrated a great potential to increase the cytotoxic effect of EPT by increasing its bioavailability.