{"title":"Urban parks biowaste as a sustainable source of new antidiabetics.","authors":"Marijan Marijan, Lejsa Jakupović, Lovorka Vujić, Marina Jurić, Marijana Zovko Končić","doi":"10.2478/acph-2024-0039","DOIUrl":"10.2478/acph-2024-0039","url":null,"abstract":"<p><p>Biowaste produced in urban parks is composed of large masses of organic matter that is only occasionally used economically. In this work, extracts of six plants widely distributed in urban parks in Central Europe (<i>Achillea millefolium</i>, <i>Cichorium intybus</i>, <i>Malva sylvestris</i>, <i>Medicago sativa</i>, <i>Plantago lanceolata</i>, and <i>Trifolium pratense</i>), prepared using 10 % and 50 % ethanol, were screened for their antidiabetic and related properties. HPLC and UV-Vis analysis revealed the presence of caffeic acid, quercetin, luteolin, and apigenin derivatives. The extracts were active in DPPH antiradical, .-carotene-linoleic acid, ORAC, and reducing power assay. They inhibited lipoxygenase, collagenase, as well as heat-induced ovalbumin coagulation. They were also able to hinder carbohydrate degradation. For example, <i>IC</i> <sub>50</sub> of anti-<i>α</i>-amylase activity of 10 % and 50 % ethanol extract of <i>M. sativa</i> extracts (204.10 ± 2.11 µg mL-1 and 78.27 ± 0.99 µg mL-1, respectively) did not statistically differ from the activity of the positive control, acarbose (284.74 ± 3.81 µg mL<sup>-1</sup>). Similar results were observed for their anti-.-glucosidase activity. In most assays, the use of 50 % ethanol was shown to be better suited for the extraction of active metabolites. The results indicate that the biowaste obtained from urban parks represents a potential source of plant material for the preparation of high-value antidiabetic products.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 4","pages":"613-633"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0020
Sinan Kandir, Sevtap Karakurt, Çiğdem Gökçek-Saraç, Serdar Karakurt
{"title":"Tannic acid elicits differential gene regulation in prostate cancer apoptosis.","authors":"Sinan Kandir, Sevtap Karakurt, Çiğdem Gökçek-Saraç, Serdar Karakurt","doi":"10.2478/acph-2024-0020","DOIUrl":"https://doi.org/10.2478/acph-2024-0020","url":null,"abstract":"<p><p>Prostate cancer is a significant global health concern that requires innovative therapeutic investigations. Here, the potential anticancer properties of tannic acid were evaluated by examining its effects on apoptosis in prostate cancer cell lines. PC-3 and LnCaP prostate adeno carcinoma cells, along with PNT1A prostate control cells, were cultured and divided into untreated and tannic acid-treated groups. Cell proliferation, cytotoxicity, and effects of tannic acid on the cell death mechanism were evaluated. mRNA expression levels of 84 genes were explored in cells following tannic acid treatment. Notably, tannic acid-induced down-regulation of several pro-survival genes, including <i>ATM, BCL2, BCL2A1, BIK, BIRC2, BIRC3, BRE, CASP3, CASP6, CASP8, CHEK2, CRADD, PPIA, RPA3, TNFSF18, TRAF1, TRAF2, TRAF4,</i> and <i>TRAF5</i> in both cell lines. Moreover, tannic acid treatment led to the up-regulation of various pro-apoptotic genes, such as <i>BCL10, BIRC3, BNIP3, CASP1, CASP5, CD40, CIDEB, DAPK2, FASLG, GADD45A, MYD88, RPA 3, TNFRSF10D, TNFRSF17, TNFRSF8, TNFSF13B, TNFSF4, TNFSF7, TNFSF8, TNFSF9, TP53, TRAF1, and TRAF2</i> in both PC-3 and LnCap cells. These findings highlight tannic acid's ability to induce apoptosis in prostate cancer cells through pro-apoptotic pathways. This study concludes that tannic acid selectively inhibits prostate cancer cell growth.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"539-550"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0027
Radek Indra, Sandra Jelínková, Katarína Kollárová, Petra Zahumenská, Josef Dvořák, Šárka Dušková, Helena Dračínská
{"title":"The tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver.","authors":"Radek Indra, Sandra Jelínková, Katarína Kollárová, Petra Zahumenská, Josef Dvořák, Šárka Dušková, Helena Dračínská","doi":"10.2478/acph-2024-0027","DOIUrl":"https://doi.org/10.2478/acph-2024-0027","url":null,"abstract":"<p><p>Lenvatinib is an orally effective tyrosine kinase inhibitor used to treat several types of tumors, including progressive, radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma. Although this drug is increasingly used in therapy, its metabolism and effects on the organism are still not described in detail. Using the rat as an experimental animal model, this study aimed to investigate the metabolism of lenvatinib by rat microsomal enzymes and cytochrome P450 (CYPs) enzymes recombinantly expressed in Supersomes<sup>TM</sup> <i>in vitro</i> and to assess the effect of lenvatinib on rat CYP expression <i>in vivo</i>. Two metabolites, <i>O</i>-desmethyl lenvatinib, and lenvatinib <i>N</i>-oxide, were produced by rat CYPs <i>in vitro</i>. CYP2A1 and 2C12 were found to be the most effective in forming <i>O</i>-desmethyl lenvatinib, while CYP3A2 was found to primarily form lenvatinib <i>N</i>-oxide. The administration of lenvatinib to rats caused changes in the expression of mRNA and protein, as well as the activity of various CYPs, particularly in an increase in CYP1A1. Thus, the administration of lenvatinib to rats has an impact on the level of CYPs.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"441-459"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0029
Saranda Disha-Ibrahimi, Gorazd Drevenšek, Martina Drevenšek, Janja Marc, Irena Prodan Žitnik
{"title":"PPIA, HRPT1, and PGK1 genes as the appropriate combination for RT-qPCR normalization in alveolar and femoral bone remodeling in olanzapine-treated rats.","authors":"Saranda Disha-Ibrahimi, Gorazd Drevenšek, Martina Drevenšek, Janja Marc, Irena Prodan Žitnik","doi":"10.2478/acph-2024-0029","DOIUrl":"https://doi.org/10.2478/acph-2024-0029","url":null,"abstract":"<p><p>Reliable gene expression analysis in bone remodeling studies requires an appropriate selection of internal controls, <i>i.e.</i> stable reference genes for the normalization of quantitative real-time PCR (RT-qPCR), the most common method used for quantifying gene expression measurements. Even the most widely used reference genes can have variable expression under different experimental conditions, or in different tissue types or treatment regimes, so selecting appropriate controls is a key step in ensuring reliable results. The aim of this research was to identify the most stable reference gene(s) for the study of olanzapine modulated bone remodeling in rats. RNA was isolated from the maxillary alveolar and femoral bones of olanzapine or placebo-treated Wistar rats and transcribed to cDNA. The expression of 12 candidate reference genes was assessed by RT-qPCR. Their expressions were analysed using GeNorm, NormFinder, BestKeeper and delta Ct algorithms, and by the comprehensive ranking method. <i>PPIA, HRPT1</i> and <i>PGK1</i> were the most stably expres sed reference genes and the combination of the three genes was optimal for normalization. This study is the first to identify the optimal reference genes for research in olanzapine-exposed rats, which serve as a pivotal benchmark for enhancing the accuracy and reliability of future RT-qPCR expression in bone studies.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"511-524"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0024
Katarina Grabrijan, Nika Strašek Benedik, Alen Krajnc, Krištof Bozovičar, Damijan Knez, Matic Proj, Irena Zdovc, Izidor Sosič, Carlos Contreras-Martel, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec
{"title":"Synthesis and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s).","authors":"Katarina Grabrijan, Nika Strašek Benedik, Alen Krajnc, Krištof Bozovičar, Damijan Knez, Matic Proj, Irena Zdovc, Izidor Sosič, Carlos Contreras-Martel, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec","doi":"10.2478/acph-2024-0024","DOIUrl":"https://doi.org/10.2478/acph-2024-0024","url":null,"abstract":"<p><p>In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from <i>Streptococcus pneumoniae</i>. Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"423-440"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs.","authors":"Xuan Fei, Lele Zixin Yang, Jingjing Zhang, Xiang Li, Mengtian Pan, Guangchen Xu, Cuixia Zhang, Fei Liu, Weirong Fang","doi":"10.2478/acph-2024-0025","DOIUrl":"https://doi.org/10.2478/acph-2024-0025","url":null,"abstract":"<p><p>Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"461-478"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0022
Blaž Lebar, Mitja Zidar, Janez Mravljak, Roman Šink, Aleš Žula, Stane Pajk
{"title":"Alternative buffer systems in biopharmaceutical formulations and their effect on protein stability.","authors":"Blaž Lebar, Mitja Zidar, Janez Mravljak, Roman Šink, Aleš Žula, Stane Pajk","doi":"10.2478/acph-2024-0022","DOIUrl":"https://doi.org/10.2478/acph-2024-0022","url":null,"abstract":"<p><p>The formulation of biopharmaceutical drugs is designed to eliminate chemical instabilities, increase conformational and colloidal stability of proteins, and optimize interfacial stability. Among the various excipients involved, buffer composition plays a pivotal role. However, conventional buffers like histidine and phosphate buffers may not always be the optimal choice for all monoclonal antibodies (mAbs). In this study, we investigated the effects of several alternative buffer systems on seven different mAbs, exploring various combinations of ionic strengths, concentrations of the main buffer component, mAb concentrations, and stress conditions. Protein stability was assessed by analyzing soluble aggregate formation through size exclusion chromatography. At low protein concentrations, protein instability after temperature stress was exclusively observed in the bis-TRIS/ glucuronate buffer. Conversely, freeze-thaw stress led to a significant increase in aggregate formation in tested formulations, highlighting the efficacy of several alternative buffers, particularly arginine/ citrate, in preserving protein stability. Under temperature stress, the introduction of arginine to histidine buffer systems provided additional stabilization, while the addition of lysine resulted in protein destabilization. Similarly, the incorporation of arginine into histi-dine/HCl buffer further enhanced protein stability during freeze--thaw cycles. At high protein concentrations, the histidine/citrate buffer emerged as one of the most optimal choices for addressing temperature and light-induced stress. The efficacy of histidine buffers in combating light stress might be attributed to the light-absorbing properties of histidine molecules. Our findings demonstrate that the development of biopharmaceutical formulations should not be confined to conventional buffer systems, as numerous alternative options exhibit comparable or even superior performance.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"479-493"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0030
Dunja Urbančič, Flaka Pasha, Alenka Šmid, Irena Mlinarič-Raščan
{"title":"Personalization of thiopurine therapy: Current recommendations and future perspectives.","authors":"Dunja Urbančič, Flaka Pasha, Alenka Šmid, Irena Mlinarič-Raščan","doi":"10.2478/acph-2024-0030","DOIUrl":"https://doi.org/10.2478/acph-2024-0030","url":null,"abstract":"<p><p>Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. This review presents the latest guidelines for thiopurine administration, highlighting the importance of individualized therapy guided by pharmacogenomics. It emphasizes dose adjustment based on nudix hydrolase 15 (<i>NUDT15</i>) and thiopurine <i>S</i>-methyltransferase (<i>TPMT</i>) genotype, along side thiopurine <i>S</i>-methyltransferase activity and thiopurine metabolic profile. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"355-381"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0019
Li Xu, Shanshan Chen, Haijun Cao, Zemin Feng, Chao Yang
{"title":"Efficacy of sorafenib plus transcatheter arterial chemoembolization in treating hepatocellular carcinoma with portal vein tumor thrombosis: A meta-analysis.","authors":"Li Xu, Shanshan Chen, Haijun Cao, Zemin Feng, Chao Yang","doi":"10.2478/acph-2024-0019","DOIUrl":"10.2478/acph-2024-0019","url":null,"abstract":"<p><p>This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28<sup>th</sup> Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507-0.685, <i>p</i> < 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205-0.553, <i>p</i> < 0.001; I<sup>2</sup> = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555-2.839, <i>p</i> < 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126-2.126, <i>p</i> = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, <i>p</i> < 0.001; I<sup>2</sup> = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"405-422"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta PharmaceuticaPub Date : 2024-09-14Print Date: 2024-09-01DOI: 10.2478/acph-2024-0021
Misbah Sultan, Shaista Parveen, Mohammad N Uddin, Farhat Jubeen, Mohsin Kazi
{"title":"Enhanced biomedical potential of polyurethane/hydroxyapatite composites through chemical modification: A comprehensive study on structure, morphology, and cytocompatibility for tissue regeneration.","authors":"Misbah Sultan, Shaista Parveen, Mohammad N Uddin, Farhat Jubeen, Mohsin Kazi","doi":"10.2478/acph-2024-0021","DOIUrl":"https://doi.org/10.2478/acph-2024-0021","url":null,"abstract":"<p><p>Polyurethane/hydroxyapatite (PU/HA) composites are well-known for various biomedical applications. This study reports a chemical approach to improve the interaction between HA and PU matrix. HA was surface-modified with 1,6-hexamethylene diisocyanate (HMDI). First, an isocyanate-modified HA (IHA) was synthesized by hydro-thermal method. Second, IHA was incorporated into a separately synthesized thermoplastic PU by a solvent casting technique. A series of PU/IHA composites was prepared by varying PU᾿s soft and hard segments. The IHA was added to PU (5 and 10 %). The FTIR spectra exhibited characteristic bands of urethane and HA, confirming the synthesis of the composites. XRD study showed the crystallite size of IHA (20 Å) with hexagonal geometry and an amorphous to semicrystalline nature of composites. SEM showed that composites displayed porous and granular morphology. The TGA thermograms of the composites revealed the thermal stability up to 400 °C. The IHA addition considerably improved hydrophilicity and degradation of the composites in simulated body fluid (SBF). MTT assay revealed improved cytocompatibility (> 80 %) of the composites. These results demonstrated an appreciable improvement in structure, morphology, hydrophilicity, degradation, and cytocompatibility of PU/IHA composites by chemical modification of HA. Hence, these composites possess remarkable potential for biomedical applications such as tissue regeneration.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"525-537"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}