<p class="ADMETkeywordsheading">Polylactic acid (PLA) is a polymer with an increased potential to be used in different medical applications, including tissue engineering and drug-carries. The use of PLA in medical applications implies the evaluation of the human organism's response to the polymer inserting and to its degradation products. Consequently, within this study, we have investigated the solubility and ADMET profiles of the short oligomers (having the molecular weight lower than 3000 Da) resulting in degradation products of PLA. There is a linear decrease of the molar solubility of investigated oligomers with molecular weight. The results that are obtained also reveal that short oligomers of PLA have promising pharmacological profiles and limited toxicological effects on humans. These oligomers are predicted as potential inhibitors of the organic anion transporting peptides OATP1B1 and OATP1B3, they present minor probability to affect the androgen and glucocorticoid receptors, have a weak potential of hepatotoxicity, and may produce eye injuries. These outcomes may be used to guide or to supplement in vitro and/or in vivo toxicity tests such as to enhance the biodegradation properties of the biopolymer.</p>
Polyhydroxyalkanoates (PHAs) are a large class of polyesters that are biosynthesized by microorganisms at large molecular weights (Mw > 80 kDa) and have a great potential for medical applications because of their recognized biocompatibility. Among PHAs, poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxyvalerate), poly(4-hydroxyvalerate), and their copolymers are proposed to be used in biomedicine, but only poly(4-hydroxybutyrate) has been certified for medical application. Along with the hydrolysis of these polymers, low molecular weight oligomers are released typically. In this study, we have used a computational approach to assess the absorption, distribution, metabolism, and excretion (ADME)-Tox profiles of low molecular weight oligomers (≤32 units) consisting of 3-hydroxybutyrate, 4-hydroxybutyrate, 3-hydroxyvalerate, 4-hydroxyvalerate, 3-hydroxybutyrate-co-3-hydroxyvalerate, and the hypothetical PHA consisting of 4-hydroxybutyrate-co-4-hydroxyvalerate. According to our simulations, these oligomers do not show cardiotoxicity, hepatotoxicity, carcinogenicity or mutagenicity, and are neither substrates nor inhibitors of the cytochromes involved in the xenobiotic’s metabolism. They also do not affect the human organic cation transporter 2 (OCT2). However, they are considered to be inhibitors of the organic anion transporters OATP1B1, and OATP1B3. In addition, they may produce eye irritation, and corrosion, skin irritation and have a low antagonistic effect on the androgen receptor.
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