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Following our previous studies on the molecular level structure of (co)oligoesters obtained via anionic homo- and co-polymerization of novel ß-substituted ß-lactones, prepared by the atmospheric pressure carbonylation reaction of respective epoxides, the boric acid biocatalyzed ring-opening (co)polymerization of δ-valerolactone has been studied. As a co-monomer the 6-methy-ε-caprolactone, prepared by the one-pot oxidation of respective alcohol, and ethylene glycol as polymerization initiator were used. The obtained copolymers were characterized by 1H-NMR, GPC and ESI-MS, respectively in order to confirm their chemical structures and identity. Subsequently, tandem mass spectrometry (MS-MS studies) via collision-induced dissociation were utilized to characterize the fragmentation pattern. ESI-MS and NMR analyses confirmed the formation of random linear copolymer chains composed of different polyester repeat units. MS-MS experiments showed that fragmentation proceeds via ester bound cleavage along the (co)polyester chains. The innovative aspect of this contribution is related to the elaboration of the telechelic (co)polymers end-capped with hydroxyl end groups and well-defined molecular architectures, which could facilitate the development of new flexible macromolecular systems for potential biomedical applications.

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This article reports the studies on bioactive (co)oligoesters towards their use as controlled delivery systems of p-anisic acid. The objects of the study were oligo[3-hydroxy-3-(4-methoxybenzoyloxymethyl)propionate], (p-AA-CH2-HP)n oligoester, and oligo[(3-hydroxy-3-(4-methoxybenzoyloxymethyl)propionate)-co-(3-hydroxybutyrate)] [(p-AA-CH2-HP)x-co-(HB)y (co)oligoesters containing p-anisic acid moiety (p-AA, as the bioactive end and side groups) connected to the polymer backbone through the susceptible to hydrolysis ester bonds. A thorough insight into the hydrolysis process of the bioactive (co)oligoesters studied has allowed us to determine the release profile of p-AA as well as to identify polymer carrier degradation products. The p-AA release profiles determined on the basis of high-performance liquid chromatography (HPLC) measurements showed that the release of the bioactive compound from the developed (co)oligoester systems was regular and no burst effect occurred. Biological studies demonstrated that studied (homo)- and (co)oligoesters were well tolerated by HaCaT cells because none of them showed notable cytotoxicity. They promoted keratinocyte growth at moderate concentrations. Bioactive (co)oligoesters containing p-anisic acid moiety had somewhat decreased cell proliferation at the highest concentration (100 µg/mL). The important practical inference of the current study is that the (co)oligoesters developed have a relatively large load of the biologically active substance (p-AA) per polymer macromolecule, which unlocks their potential application in the cosmetic industry.

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Periodontitis (PD) is a chronic inflammatory disease of periodontal tissues caused by pathogenic microorganisms and characterized by disruption of the tooth-supporting structures. Conventional drug administration pathways in periodontal disease treatment have many drawbacks such as poor biodistribution, low selectivity of the therapeutic effect, burst release of the drug, and damage to healthy cells. To overcome this limitation, controlled drug delivery systems have been developed as a potential method to address oral infectious disease ailments. The use of drug delivery devices proves to be an excellent auxiliary method in improving the quality and effectiveness in periodontitis treatment, which includes inaccessible periodontal pockets. This review explores the current state of knowledge regarding the applications of various polymer-based delivery systems such as hydrogels, liposomes, micro-, and nanoparticles in the treatment of chronic periodontal disease. Furthermore, to present a more comprehensive understanding of the difficulties concerning the treatment of PD, a brief description of the mechanism and development of the disease is outlined.

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INTRODUCTION: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical man-agement. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies. In this study we used mass spectrometry imaging to detect lipids discriminating papillary cancer from not cancerous thyroid directly in formalin-fixed tissue sections. MATERIAL AND METHODS: For this purpose imaging and profiling of lipids present in non-malignant and cancerous thyroid tissue specimens were conducted. High resolution MALDI-Q-Ion Mobility-TOF-MS technique was used for lipidomic analysis of formalin fixed thyroid tissue samples. Lipids were identified by the comparison of the exact molecular masses and fragmentation pathways of the protonated molecule ions, recorded during the MS/MS experiments, with LIPID MAPS database. RESULTS: Several phosphatidylcholines (32:0, 32:1, 34:1 and 36:3), sphingomyelins (34:1 and 36:1) and phosphatidic acids (36:2 and 36:3) were detected and their abundances were significantly higher in cancerous tissue compared to non-cancerous tissue. The same lipid species were detected in formalin-fixed as in fresh-frozen tissue, but [M + Na]+ ions were the most abundant in formalin fixed whereas [M + K]+ ions were predominant in fresh tissue. CONCLUSIONS: Our results prove the viability of MALDI-MSI for analysis of lipid distribution directly in formalin-fixed tissue, and the potential for their use in the classification of thyroid diseases.

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Conjugates of antioxidants p-anisic (p-AA) and vanillic (VA) acids with nontoxic, biocompatible, and biodegradedable oligo-(R,S)-(3-hydoxybutyrate) carrier were synthesized, and their structural and biological characterization was performed. The molecular structure of the bioconjugates, in which antioxidants are covalently bonded with oligo(3-hydroxybutyrate) (OHB) chains, has been proven by mass spectrometry supported by NMR. The bioconjugate hydrolytic degradation studies allowed gaining thorough insight into the hydrolysis process and confirmed the release of p-AA and VA. In vitro studies demonstrated that all of the conjugates studied were well tolerated by KB and HaCaT cell lines, as they had no marked cytotoxicity, while conjugates with a relatively short OHB carrier are optimal to support keratinocyte function. The preliminary study of the biological activity confirmed the protective effect of VA-OHB conjugates against H2O2-induced lipid peroxidation in human keratinocytes (HaCaT). It was also demonstrated that the selected bioconjugates can penetrate all layers of the skin, which shows their functionality and opens up their potential application in cosmetology.

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The present study focuses on electrospray ionisation (ESI) tandem mass spectrometry of novel copolyesters obtained by anionic ring-opening copolymerisation of ß-substituted ß-lactones. Detailed analysis of these copolyesters, including molecular chain architecture as well as the structures of the end groups, was performed using ESI-MS/MS collision-induced dissociation spectra. The random arrangement of comonomeric units along the copolyester chains was demonstrated by comparison of ESI-MS(n) fragmentation spectra and fragmentation pathways. Sequence distribution analysis of comonomeric units confirmed the copolymer's random structure. ESI-MS(n) proved to be a promising technique for structural analysis of copolyesters obtained via anionic ROP.

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RATIONALE: Currently, most of the antioxidants and free radical neutralizers used in cosmetic compositions are absorbed quickly into deeper layers of skin, and then carried away by the blood stream. It would be beneficial to delay the penetration of antioxidants to the deeper layers of skin to control their delivery and release. METHODS: Recently, growing attention has been paid to the attachment of cosmetics to specific polymer carriers. Biodegradable and biocompatible conjugates of oligo-3-hydroxybutyrate with lipoic acid were obtained via the anionic ring-opening oligomerization of (R,S)-ß-butyrolactone initiated by lipoic acid potassium salt. The structure of the resulting conjugates as well as their water-soluble hydrolytic degradation products were established at the molecular level by electrospray ionization mass spectrometry (ESI-MS(n)) supported by (1)H NMR analyses. RESULTS: The structural studies, performed with the aid of ESI-MS(n), confirmed that the lipoic acid was covalently bound to oligo-3-hydroxybutyrate chains through hydrolyzable ester bonds. Furthermore, hydrolytic degradation studies of the bioconjugates provided detailed insight into the hydrolysis process, allowing the identification of the degradation products and confirming the release of α-lipoic acid. Cytotoxicity tests demonstrated that the conjugates were non-toxic. CONCLUSIONS: Detailed molecular structural studies of new polymeric delivery systems of lipoic acid were performed by ESI-MS. ESI-MS proved to be an excellent technique for the evaluation of hydrolytic degradation products of the conjugates and for monitoring the release of lipoic acid. The results obtained contribute significantly to the characterization of biocompatible LA-OHB conjugates with potential applications in cosmetology.

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