Pharmaceutical frontiers最新文献

Use of Gelatin as Tannic Acid Carrier for Its Sustained Local Delivery 明胶作为单宁酸持续局部输送载体的研究

Pharmaceutical frontiers Pub Date : 2020-01-29 DOI: 10.20900/pf20200002

Francois Reitzer, Emine Berber, Juliette Halgand, V. Ball, F. Meyer

{"title":"Use of Gelatin as Tannic Acid Carrier for Its Sustained Local Delivery","authors":"Francois Reitzer, Emine Berber, Juliette Halgand, V. Ball, F. Meyer","doi":"10.20900/pf20200002","DOIUrl":"https://doi.org/10.20900/pf20200002","url":null,"abstract":"Background: Polyphenols are macromolecules that play a pivotal role in plant protection against external aggression from microorganisms or radiations. Their antimicrobial properties have raised interest in the medical community for several years now. Among them, tannic acid is one of the cheapest polyphenols extracted from plants. However, its broad use is impeded because it is unstable, with rapid hydrolysis leading to byproducts such as epigallocatechin with less activity. In this work, we developed a porous material to deliver locally tannic acid. \u0000Methods: The preparation of this matrix relied on the interaction between gelatin and tannic acid in an aqueous medium. Structure properties of the developed matrix were investigated through rheology measurement and by scanning electron microscopy (SEM). Tannic acid quantity and release over time were measured. Antimicrobial activity was tested in vitro on E. coli and S. aureus. \u0000Results: The presence of two tannic acid populations, one free to diffuse across the scaffold and the second stabilized by gelatin with a more structural activity, was demonstrated. We showed that the formulation is possible above a molar ratio of 1:15 (gelatin:tannic acid). Gelatin was used here as a carrier for the tannic acid. Tannic acid content could be modulated depending on its initial concentration during the preparation. Tannic acid was released from these matrices over a period of four days at a concentration that was above the minimum inhibitory concentration (MIC). Antimicrobial activity was confirmed on E. coli and S. aureus. The porous material could be conserved by lyophilization without loss of activity. Its handiness is good enough to consider its use as a wound dressing. \u0000Conclusions: We demonstrate herein an easy and cost-effective protocol to locally deliver tannic acid.","PeriodicalId":92834,"journal":{"name":"Pharmaceutical frontiers","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82331842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Desolvation Conditions for Production of Sulfasalazine Based Albumin Nanoparticles: Physical Properties 磺胺吡啶基白蛋白纳米颗粒的脱溶条件:物理性质

Pharmaceutical frontiers Pub Date : 2019-08-14 DOI: 10.20900/PF20190006

Victor Olaitan, C. Chaw

{"title":"Desolvation Conditions for Production of Sulfasalazine Based Albumin Nanoparticles: Physical Properties","authors":"Victor Olaitan, C. Chaw","doi":"10.20900/PF20190006","DOIUrl":"https://doi.org/10.20900/PF20190006","url":null,"abstract":"Background: Albumin-based nanoparticles have been used as drug carriers to improve therapeutic effect. This study aimed to produce sulfasalazine (SSZ)-loaded bovine serum albumin (BSA) nanoparticles by desolvation technique and characterize their physical properties. Drug loading effect was also investigated. \u0000Methods: SSZ albumin nanoparticles were batch produced by desolvation technique and lyophilized. Physical characteristics of nanoparticles including size distribution, zeta potential and entrapment efficiency were studied. \u0000Results: Nanoparticles were spherical and typically 200–400 nm with low polydispersity (PDI). The zeta potentials of nanoparticles ranged from −21 to −41 mV, which were attributed to BSA and SSZ. The highest actual drug loading was close to 0.5%w/w. The addition of 2% sucrose during lyophilization was essential to avoid cake collapse and the particle sizes increased slightly where their PDI values were low. Although the presence of sucrose led to a slight reduction in zeta potential, it had limited effect on zeta potential of the nanoparticles. The interactions between SSZ and formulation excipients were also confirmed with FTIR and DSC analyses. \u0000Conclusion: Desolvation technique produced stable sulfasalazine-loaded nanoparticles that can be administered parenterally.","PeriodicalId":92834,"journal":{"name":"Pharmaceutical frontiers","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74212042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

The Cancer Cell Killing Effects of Gynura procumbens, Toleaf Are Associated with CD4+ T Lymphocyte Activation 黄芪、黄芪对癌细胞的杀伤作用与CD4+ T淋巴细胞活化有关

Pharmaceutical frontiers Pub Date : 2019-06-21 DOI: 10.20900/PF20190004

K. Takanashi, K. Dan, T. Matsuoka, K. Torii

{"title":"The Cancer Cell Killing Effects of Gynura procumbens, Toleaf Are Associated with CD4+ T Lymphocyte Activation","authors":"K. Takanashi, K. Dan, T. Matsuoka, K. Torii","doi":"10.20900/PF20190004","DOIUrl":"https://doi.org/10.20900/PF20190004","url":null,"abstract":"Background: Toleaf is a cold abstraction extract from the Gynura procumbens (Lour.) Merr. plant. Compounds extracted from G. procumbens exert anti-cancer effects against various cancers. However, detailed mechanisms underlying these actions remain unclear. Previous research indicated that G. procumbens ethanol extracts also have immunomodulatory properties. Therefore, we examined the relationship between Toleaf’s anti-cancer effects and immune system responses in vitro and ex vivo. Methods: Effects of Toleaf on immune response were assessed using ELISA, RT-PCR, and flow cytometry to measure IFN-γ, IL-2, IL-4, and IL-12 expression in primary splenic cells obtained from 6-week-old male BALB/c or C57BL/6 mice and in T lymphocytes isolated from mouse splenic cells. Toleaf’s anti-cancer and T-cell activation effects were evaluated by determining CT-26, EL-4, and B16 cancer cell viability. Results: Toleaf treatment increased splenic cell IFN-γ production and CD4+ T lymphocyte IL-2, IL-4, and IL-12-mRNA levels. All three cancer cell lines exhibited decreased viability after exposure to Toleaf-treated T lymphocytes. However, Toleaf did not exert direct cytotoxic effects on these cells. \u0000Conclusions: Toleaf activates type 1 and 2 T helper responses, suggesting that its anti-cancer effects are associated with CD4+ T lymphocyte activation.","PeriodicalId":92834,"journal":{"name":"Pharmaceutical frontiers","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87386402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Safety Implications of Low-Dose Amitriptyline in Neuropathic Pain 低剂量阿米替林治疗神经性疼痛的安全性影响

Pharmaceutical frontiers Pub Date : 2019-05-28 DOI: 10.20900/PF20190003

L. Buhagiar, Marilyn Casha, A. Grech, Benjamin Micallef, J. Borg, A. Inglott, G. Laferla

{"title":"Safety Implications of Low-Dose Amitriptyline in Neuropathic Pain","authors":"L. Buhagiar, Marilyn Casha, A. Grech, Benjamin Micallef, J. Borg, A. Inglott, G. Laferla","doi":"10.20900/PF20190003","DOIUrl":"https://doi.org/10.20900/PF20190003","url":null,"abstract":"Background: Treatment guidelines in neuropathic pain list amitriptyline as a first-line option. Modest evidence on efficacy and safety concerns possibly shape the rationale behind dosing recommendations. An observational study was carried out to understand the usefulness of safety monitoring for this established medicine. Methods: Twenty-six (26) subjects were categorized into 2 groups: 13 patients under pain management receiving 10 mg amitriptyline daily for less than 12 months, and 13 patients under psychiatric care receiving a daily dose of 25–75 mg for over 12 months. Dose-related reference ranges were calculated and blood levels were assessed for the case examples presented. Adverse events and ECGs were collated. QT intervals were corrected using Bazett’s and Fridericia’s formulae. Side-effect frequencies were evaluated both within the research groups, and in the broader perspective of spontaneous ADR reporting through EudraVigilance. Results: The applicability of dose-related reference ranges, considering confounding factors such as drug interactions and metabolizer status, is discussed. Patients in both groups reported on average three side-effects, with drowsiness being reported more significantly in the 10 mg group and possibly attenuating with time; an observation not replicated for dry mouth. ADR reports with non-granulated information limit the usefulness of the data retrieved. Comparison of QT corrected with Bazett’s and Fridericia’s formulae suggests that Bazett’s may overestimate the number of patients on amitriptyline with QTc prolongation. Conclusions: This research supports the adoption of evolving research observations to understand the implications of dosing recommendations and safety assessments in attempt of delivering individualized treatment with minimal risk","PeriodicalId":92834,"journal":{"name":"Pharmaceutical frontiers","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84115562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Generation of a Small Library of Natural Products Designed to Cover Chemical Space Inexpensively. 一个小型天然产品库的生成，旨在以低成本覆盖化学空间。

Pharmaceutical frontiers Pub Date : 2019-01-01 Epub Date: 2019-08-09 DOI: 10.20900/pf20190005

Steve O'Hagan, Douglas B Kell

{"title":"Generation of a Small Library of Natural Products Designed to Cover Chemical Space Inexpensively.","authors":"Steve O'Hagan, Douglas B Kell","doi":"10.20900/pf20190005","DOIUrl":"10.20900/pf20190005","url":null,"abstract":"Natural products space includes at least 200,000 compounds and the structures of most of these compounds are available in digital format. Previous analyses showed (i) that although they were capable of taking up synthetic pharmaceutical drugs, such exogenous molecules were likely the chief 'natural' substrates in the evolution of the transporters used to gain cellular entry by pharmaceutical drugs, and (ii) that a relatively simple but rapid clustering algorithm could produce clusters from which individual elements might serve to form a representative library covering natural products space. This exploited the fact that the larger clusters were likely to be formed early in evolution (and hence to have been accompanied by suitable transporters), so that very small clusters, including singletons, could be ignored. In the latter work, we assumed that the molecule chosen might be that in the middle of the cluster. However, this ignored two other criteria, namely the commercial availability and the financial cost of the individual elements of these clusters. We here develop a small representative library in which we to seek to satisfy the somewhat competing criteria of coverage ('representativeness'), availability and cost. It is intended that the library chosen might serve as a testbed of molecules that may or may not be substrates for known or orphan drug transporters. A supplementary spreadsheet provides details, and their availability via a particular supplier.","PeriodicalId":92834,"journal":{"name":"Pharmaceutical frontiers","volume":"1 1","pages":"e190005"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89763813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liposome Delivery of Natural STAT3 Inhibitors for the Treatment of Cancer. 天然STAT3抑制剂的脂质体递送治疗癌症。

Pharmaceutical frontiers Pub Date : 2019-01-01 Epub Date: 2019-11-28 DOI: 10.20900/pf20190007

Max Kullberg, Alexandra Francian, Ameneh Arabi, Troy Olsson, Kristine Mann, Holly A Martinson

{"title":"Liposome Delivery of Natural STAT3 Inhibitors for the Treatment of Cancer.","authors":"Max Kullberg, Alexandra Francian, Ameneh Arabi, Troy Olsson, Kristine Mann, Holly A Martinson","doi":"10.20900/pf20190007","DOIUrl":"https://doi.org/10.20900/pf20190007","url":null,"abstract":"In the tumor microenvironment, cytokines, growth factors, and oncogenes mediate constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in both cancer cells and infiltrating immune cells. STAT3 activation in cancer cells drives tumorigenic changes that allow for increased survival, proliferation, and resistance to apoptosis. The modulation of immune cells is more complicated and conflicting. STAT3 signaling drives the myeloid cell phenotype towards an immune suppressive state, which mediates T cell inhibition. On the other hand, STAT3 signaling in T cells leads to proliferation and T cell activity required for an anti-tumor response. Targeted delivery of STAT3 inhibitors to cancer cells and myeloid cells could therefore improve therapeutic outcomes. Many compounds that inhibit the STAT3 pathways for cancer treatment include peptide drugs, small molecule inhibitors, and natural compounds. However, natural compounds that inhibit STAT3 are often hydrophobic, which reduces their bioavailability and leads to unfavorable pharmacokinetics. This review focuses specifically on liposome-encapsulated natural STAT3 inhibitors and their ability to target cancer cells and myeloid cells to reduce tumor growth and decrease STAT3-mediated immune suppression. Many of these liposome formulations have led to profound tumor reduction and examples of combination formulations have been shown to eliminate tumors through immune modulation.","PeriodicalId":92834,"journal":{"name":"Pharmaceutical frontiers","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934091/pdf/nihms-1061712.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37498552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5