Among the various biomaterials available for tissue engineering and therapeutic applications, microbial polyhydroxyalkanoates offer the most diverse range of thermal and mechanical properties. In this study, the biocompatibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB); containing 50 mol % of 4-hydroxybutyrate] copolymer produced by Delftia acidovorans was evaluated. The cytotoxicity, mode of cell death, and genotoxicity of P(3HB-co-4HB) extract against V79 and L929 fibroblast cells were assessed using MTT assay, acridine orange/propidium iodide staining, and alkaline comet assay, respectively. Our results demonstrate that P(3HB-co-4HB) treated on both cell lines were comparable with clinically-used Polyglactin 910, where more than 60% of viable cells were observed following 72-h treatment at 200 mg/mL. Further morphological investigation on the mode of cell death showed an increase in apoptotic cells in a time-dependent manner in both cell lines. On the other hand, P(3HB-co-4HB) at 200 mg/mL showed no genotoxic effects as determined by alkaline comet assay following 72-h treatment. In conclusion, our study indicated that P(3HB-co-4HB) compounds showed good biocompatibility in fibroblast cells suggesting that it has potential to be used for future medical applications.
This study aimed to investigate the oral acute and subacute toxicity of Poly [3-hydroxybutyrate-co-4-hydroxybutyrate], P(3HB-co-4HB) in the form of nanoparticles in Sprague-Dawley rats. Acute oral administration of P(3HB-co-4HB) nanoparticles was performed as a single dose up to 2000 mg/kg in six female rats for 14 days. Subacute toxicity study via oral administration for 28 days at doses of 0 (control), 500, 1000 and 2000 mg/kg in rats (10 rats in each group, female:male = 1:1) was conducted. The estimated lethal dose (LD50) of P(3HB-co-4HB) nanoparticles was >2000 mg/kg. No mortality, unusual changes in behaviour, adverse clinical signs, abnormal changes in body weights or food consumption were observed on all animals treated with P(3HB-co-4HB) nanoparticles during 14 days of the acute toxicity study. In the subacute test, there was no mortality and toxicologically significant changes in clinical signs, body weights, food consumption, hematology, clinical biochemistry, urinalysis, macroscopic findings, organ weights as well as histopathological examination were observed.
Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.