Solubility and ADMET profiles of short oligomers of lactic acid

Dascălu, Daniela; Roman, Diana Larisa; Filip, Mǎdǎlina; Ciorsac, Alecu; Ostafe, Vasile; Isvoran, Adriana

doi:10.5599/admet.843

Cited by 13 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quite similar results with those emphasized in this study were obtained when assessing the pharmacological profiles of the short oligomers resulting from the degradation of other biopolymers that are used for medical applications: oligomers (up to 40 monomeric units) of lactic acid (OLAs) (Dascalu et al, 2020) and low molecular weight chito-oligosaccharides (Roman et al, 2019). OLAs were also predicted as being able to inhibit the organic anion transporting peptides OATP1B1 and/or OATP1B3.…”

Section: O4hbv O4hvb O4hbvb O4hbvv 04hvbv O4hvbbsupporting

confidence: 84%

“…The co-oligomers containing the sequences 3-hydroxybutyrate-3-hydroxyvalerate or 4-hydroxybutyrate-4hydroxyvalerate revealed to have the highest probabilities to bind to plasma proteins. Low probabilities to bind to plasma proteins have been also predicted for low molecular weight chitosan based oligomers (Roman et al, 2019) and low molecular weight oligomers of lactic acid (Dascalu et al, 2020). This outcome is also in good agreement with the information that the binding of 4HB to plasma proteins is negligible and its distribution on the human organism depends on its distribution in the total body water (Busardò and Jones, 2015).…”

Section: O4hbv O4hvb O4hbvb O4hbvv 04hvbv O4hvbbsupporting

confidence: 79%

“…the pharmacological profiles and toxicological endpoints of water-soluble chitosan derivatives (Isvoran et al, 2017), steroids (Roman et al, 2018a), parabens (Roman et al, 2018b), chito-oligomers (Roman et al, 2019), phthalates (Craciun et al, 2019), pesticides (Alves et al, 2018b;Gridan et al, 2019), and low molecular weight oligomers of lactic acid (Dascalu et al, 2020). These methods are summarized in Table 2.…”

Section: Computational Toolmentioning

confidence: 99%

See 2 more Smart Citations

In silico Assessment of Pharmacological Profile of Low Molecular Weight Oligo-Hydroxyalkanoates

Roman

Isvoran

Filip

et al. 2020

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: O4hbv O4hvb O4hbvb O4hbvv 04hvbv O4hvbbsupporting

confidence: 84%

Section: O4hbv O4hvb O4hbvb O4hbvv 04hvbv O4hvbbsupporting

confidence: 79%

Section: Computational Toolmentioning

confidence: 99%

See 1 more Smart Citation

In silico Assessment of Pharmacological Profile of Low Molecular Weight Oligo-Hydroxyalkanoates

Roman

Isvoran

Filip

et al. 2020

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Prediction of ADMET profile is mainly based on models of the physicochemical properties of chemicals which influence much of their pharmacokinetics, but there are also prediction models of the endpoints in ADME that are based on both in vitro and in vivo assay results [23][24][25][26].…”

Section: K1 K2mentioning

confidence: 99%

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

et al. 2021

View full text Add to dashboard Cite

Background and Objectives: The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity; thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods: The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results: ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity; thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions: The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact.

show abstract

“…They observed statistically significant differences between USP Apparatus 1 and 2, whereas conditions producing similar dissolution profiles for USP Apparatus 2 and 4 were identified. In the paper authored by Isvoran et al [16] solubility of short oligomers of lactic acid is studied. Polylactic acid has potential to be used in medical applications, and hence the solubility of this polymer is important.…”

mentioning

confidence: 99%