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[PMID]: 28110039 [Au] Autor: Ganguly R; Kunwar A; Dutta B; Kumar S; Barick KC; Ballal A; Aswal VK; Hassan PA [Ad] Endereço: Chemistry Division, Bhabha Atomic Research Center, Mumbai, 400085, India. Electronic address: rajibg@barc.gov.in. [Ti] Título: Heat-induced solubilization of curcumin in kinetically stable pluronic P123 micelles and vesicles: An exploit of slow dynamics of the micellar restructuring processes in the aqueous pluronic system. [So] Source: Colloids Surf B Biointerfaces;152:176-182, 2017 Apr 01. [Is] ISSN: 1873-4367 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Wide therapeutic potential combined with low cost and negligible toxicity makes curcumin one of the most sought after drugs in recent times. Its poor aqueous solubility and low bioavailability are often overcome by using micelles and vesicles as its carriers. The substances that are commonly used for this purpose are a class of nonionic surfactants called pluronics. Solubilization of curcumin in aqueous systems of these surfactants is carried out by thin film hydration method presumably because slow dynamics of micellar restructuring processes in them creates hindrance for direct solubilization. In this manuscript, we show that this problem can be overcome and curcumin can be solubilized directly in pluronic P123 micellar solutions by heating them to the phase separation temperature in the presence of curcumin. The obtained curcumin containing micellar solutions show cytotoxicity on human breast carcinoma (MCF7) cells with IC values similar to that shown by free curcumin solution. Addition of mucoadhesive polymer κ-Carrageenan into these solutions converts them to curcumin containing gels and patches with rheological properties suitable for topical application. These solutions also exhibit systematic spherical-to-worm like micellar-to-vesicular structural transitions in the presence of NaCl. The large curcumin containing aggregates thus formed show kinetic stability with respect to dilution, which is an important attribute for drug delivery application. Characterization of the micellar and vesicular systems and gels were carried out by SANS, DLS and rheological measurements. The obtained results represent first systematic study on solubilization of curcumin in pluronic aggregates of various shapes and size. [Mh] Termos MeSH primário: Curcumina/química Temperatura Alta Micelas Poloxaleno/química [Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos Curcumina/toxicidade Seres Humanos Hidrogel de Polietilenoglicol-Dimetacrilato/química Cinética Células MCF-7 [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Micelles); 0 (pluronic block copolymer P123); 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate); 9003-11-6 (Poloxalene); IT942ZTH98 (Curcumin) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170123 [St] Status: MEDLINE

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[PMID]: 28012929 [Au] Autor: Demirci S; Dogan A; Türkmen NB; Telci D; Rizvanov AA; Sahin F [Ad] Endereço: Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey; National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, United States. [Ti] Título: Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro. [So] Source: Biomed Pharmacother;86:492-501, 2017 Feb. [Is] ISSN: 1950-6007 [Cp] País de publicação: France [La] Idioma: eng [Ab] Resumo: Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. [Mh] Termos MeSH primário: Antineoplásicos/química Antineoplásicos/farmacologia Poloxaleno/química Poloxâmero/química Neoplasias da Próstata/tratamento farmacológico Bases de Schiff/química [Mh] Termos MeSH secundário: Animais Apoptose/efeitos dos fármacos Linhagem Celular Tumoral Movimento Celular/efeitos dos fármacos Proliferação Celular/efeitos dos fármacos Seres Humanos Masculino Camundongos Polietilenoglicóis/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Schiff Bases); 0 (pluronic block copolymer p85); 106392-12-5 (Poloxamer); 30IQX730WE (Polyethylene Glycols); 9003-11-6 (Poloxalene) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 170208 [Lr] Data última revisão: 170208 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161226 [St] Status: MEDLINE

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[PMID]: 27987651 [Au] Autor: Pellosi DS; Calori IR; de Paula LB; Hioka N; Quaglia F; Tedesco AC [Ad] Endereço: Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto, Brazil. [Ti] Título: Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells. [So] Source: Mater Sci Eng C Mater Biol Appl;71:1-9, 2017 Feb 01. [Is] ISSN: 1873-0191 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Nanotechnology development provides new strategies to treat cancer by integration of different treatment modalities in a single multifunctional nanoparticle. In this scenario, we applied the multifunctional Pluronic P123/F127 mixed micelles for Verteporfin-mediated photodynamic therapy in PC3 and MCF-7 cancer cells. Micelles functionalization aimed the targeted delivery by the insertion of biotin moiety on micelle surface and fluorescence image-based through rhodamine-B dye conjugation in the polymer chains. Multifunctional Pluronics formed spherical nanoparticulated micelles that efficiently encapsulated the photosensitizer Verteporfin maintaining its favorable photophysical properties. Lyophilized formulations were stable at least for 6months and readily reconstituted in aqueous media. The multifunctional micelles were stable in protein-rich media due to the dual Pluronic mixed micelles characteristic: high drug loading capacity provided by its micellar core and high kinetic stability due its biocompatible shell. Biotin surface functionalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhodamine B-tagged micelles allowed monitoring cellular uptake and intracellular distribution of the formulations. Confocal microscopy studies demonstrated a larger intracellular distribution of the formulation and photosensitizer, which could drive Verteporfin to act on multiple cell sites. Formulations were not toxic in the dark condition, but showed high Verteporfin-induced phototoxicity against both cancer cell lines at low drug and light doses. These results point Verteporfin-loaded multifunctional micelles as a promising tool to further developments in photodynamic therapy of cancer. [Mh] Termos MeSH primário: Portadores de Fármacos Micelas Nanopartículas/química Neoplasias/tratamento farmacológico Fotoquimioterapia Poloxaleno Poloxâmero Porfirinas Nanomedicina Teranóstica/métodos [Mh] Termos MeSH secundário: Portadores de Fármacos/química Portadores de Fármacos/farmacocinética Portadores de Fármacos/farmacologia Feminino Seres Humanos Células MCF-7 Masculino Neoplasias/metabolismo Neoplasias/patologia Poloxaleno/química Poloxaleno/farmacocinética Poloxaleno/farmacologia Poloxâmero/química Poloxâmero/farmacocinética Poloxâmero/farmacologia Porfirinas/química Porfirinas/farmacocinética Porfirinas/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Drug Carriers); 0 (Micelles); 0 (Porphyrins); 0 (pluronic block copolymer P123); 0X9PA28K43 (verteporfin); 106392-12-5 (Poloxamer); 9003-11-6 (Poloxalene) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170926 [Lr] Data última revisão: 170926 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161219 [St] Status: MEDLINE

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[PMID]: 27917871 [Au] Autor: Zhu JJ; Zhang XX; Miao YQ; He SF; Tian DM; Yao XS; Tang JS; Gan Y [Ad] Endereço: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Ji-nan University, Guangzhou 510632, China. [Ti] Título: Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells. [So] Source: Acta Pharmacol Sin;38(2):290-300, 2017 Feb. [Is] ISSN: 1745-7254 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40-50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC =2.94 µmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC values (0.76 and 1.44 µmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects. [Mh] Termos MeSH primário: Glicosídeos Cardíacos/administração & dosagem Glicosídeos Cardíacos/farmacologia Portadores de Fármacos/química Micelas Poloxaleno/química [Mh] Termos MeSH secundário: Animais Glicosídeos Cardíacos/uso terapêutico Linhagem Celular Tumoral Quitosana/química Seres Humanos Camundongos Tamanho da Partícula Ensaios Antitumorais Modelo de Xenoenxerto [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cardiac Glycosides); 0 (Drug Carriers); 0 (Micelles); 0 (acetylthevetin B); 0 (pluronic block copolymer P123); 9003-11-6 (Poloxalene); 9012-76-4 (Chitosan) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170912 [Lr] Data última revisão: 170912 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161206 [St] Status: MEDLINE [do] DOI: 10.1038/aps.2016.113

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[PMID]: 27912181 [Au] Autor: Wolf-Márquez VE; Martínez-Trujillo MA; Aguilar Osorio G; Patiño F; Álvarez MS; Rodríguez A; Sanromán MÁ; Deive FJ [Ad] Endereço: División de Ingeniería Química y Bioquímica, Tecnológico de Estudios Superiores de Ecatepec, CP 55210 México D.F., Mexico; Departamento de Ingeniería Química, Campus Lagoas Marcosende, Universidad de Vigo, Vigo 36310, Spain. [Ti] Título: Scaling-up and ionic liquid-based extraction of pectinases from Aspergillus flavipes cultures. [So] Source: Bioresour Technol;225:326-335, 2017 Feb. [Is] ISSN: 1873-2976 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The viability of the scaling-up of pectinases production by Aspergillus flavipes at 5L-bioreactor scale has been demonstrated by keeping constant the power input, and a drastic increase in the endo- and exopectinolytic enzyme production was recorded (7- and 40-fold, respectively). The main process variables were modelled by means of logistic and Gompertz equations. In order to overcome the limitations of the conventional downstream strategies, a novel extraction strategy was proposed on the basis of the adequate salting-out potential of two biocompatible cholinium-based ionic liquids (N Cl and N H PO ) in aqueous solutions of Tergitol, reaching more than 90% of extraction. [Mh] Termos MeSH primário: Aspergillus/química Microbiologia Industrial/métodos Líquidos Iônicos/química Poligalacturonase/isolamento & purificação Poligalacturonase/metabolismo [Mh] Termos MeSH secundário: Aspergillus/metabolismo Reatores Biológicos Fracionamento Químico/métodos Microbiologia Industrial/instrumentação Poloxaleno/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Ionic Liquids); 9003-11-6 (Poloxalene); EC 3.2.1.15 (Polygalacturonase) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 170213 [Lr] Data última revisão: 170213 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161203 [St] Status: MEDLINE

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[PMID]: 27827005 [Au] Autor: Tomoda K; Chiang HC; Kozak KR; Kwon GS [Ad] Endereço: a Pharmaceutical Sciences Division, School of Pharmacy , University of Wisconsin , Madison , USA. [Ti] Título: Injectable (-)-gossypol-loaded Pluronic P85 micelles for cancer chemoradiotherapy. [So] Source: Int J Radiat Biol;93(4):402-406, 2017 Apr. [Is] ISSN: 1362-3095 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: PURPOSE: The aim of tumor-specific chemoradiotherapy is to achieve synergistic anticancer effects with clinically acceptable toxicity. Our previous studies showed that Pluronic P85 augments radiation cancer cell killing of (±)-gossypol in vitro. In this study, the radiosensitizing effect of (-)-gossypol, more potent Bcl protein inhibitor, with Pluronic P85 was investigated. MATERIALS AND METHODS: The inhibitory effect of (-)-gossypol solubilized Pluronic P85 with 0-8 Gy of radiation on clonogenic survival rate of A549 human lung adenocarcinoma cells was investigated in vitro. The anticancer effect of (-)-gossypol-solubilized Pluronic P85 with fractionated radiation of 15 Gy was assessed by A549 tumor-bearing mice. RESULTS: (-)-Gossypol-loaded Pluronic P85 was found to be a more potent radiosensitizer in vitro. Pluronic P85 increased the anti-proliferative activity of (-)-gossypol against A549 cells (82 ± 42 versus 190 ± 60 nM). In addition, the combination of P85 and (-)-gossypol effectively reduced clonogenic survival of A549 cells: (11 ± 5%) compared to (-)-gossypol and P85 alone (62 ± 27% and 93 ± 13%, respectively), and enhanced radiation cancer cell killing. In vivo, P85 (200 mg/kg/day) and (-)-gossypol (15 mg/kg/day) could be safely injected intravenously over 5 days and enhanced radiation-related tumor control in an A549 xenograft model. CONCLUSION: Pluronic P85 and (-)-gossypol act as a novel dual agent radiosensitizer and holds promise as a chemoradiotherapeutic strategy. [Mh] Termos MeSH primário: Quimiorradioterapia/métodos Gossipol/administração & dosagem Neoplasias Experimentais/patologia Neoplasias Experimentais/terapia Poloxaleno/administração & dosagem Radiossensibilizantes/administração & dosagem [Mh] Termos MeSH secundário: Células A549 Animais Antineoplásicos/administração & dosagem Sobrevivência Celular/efeitos dos fármacos Sobrevivência Celular/efeitos da radiação Relação Dose-Resposta a Droga Feminino Camundongos Camundongos Nus Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Radiation-Sensitizing Agents); 0 (pluronic block copolymer p85); 9003-11-6 (Poloxalene); KAV15B369O (Gossypol) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: IM; S [Da] Data de entrada para processamento: 161110 [St] Status: MEDLINE [do] DOI: 10.1080/09553002.2016.1257833

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[PMID]: 27662855 [Au] Autor: Marien CBD; Marchal C; Koch A; Robert D; Drogui P [Ad] Endereço: Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé (ICPEES), CNRS-UMR7515-University of Strasbourg, Saint-Avold Antenna, Université de Lorraine, 12 rue Victor Demange, 57500, Saint-Avold, France. cdric.ma@gmail.com. [Ti] Título: Sol-gel synthesis of TiO nanoparticles: effect of Pluronic P123 on particle's morphology and photocatalytic degradation of paraquat. [So] Source: Environ Sci Pollut Res Int;24(14):12582-12588, 2017 May. [Is] ISSN: 1614-7499 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: We report a facile method to tune TiO nanoparticles' morphology by modifying and an acid-catalyzed sol-gel synthesis with Pluronic P123. Synthesized particles were characterized by transmission electron microscopy, BET analysis, and X-ray diffraction spectroscopy. XRD analysis revealed a high anatase content while BET measurements showed that porous volume strongly depends on the amount of P123. We demonstrate that high amounts of P123 increase particle's aspect-ratio from spherical to rod-shape morphology. We evaluated the photocatalytic performances for the removal of methyl viologen (paraquat) and found that best performances are obtained for the following weight ratio P123/TiO = 7.5. Furthermore, P25 is less active than synthesized nanoparticles. [Mh] Termos MeSH primário: Luz Paraquat/química [Mh] Termos MeSH secundário: Catálise Nanopartículas/química Poloxaleno Titânio/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (pluronic block copolymer P123); 15FIX9V2JP (titanium dioxide); 9003-11-6 (Poloxalene); D1JT611TNE (Titanium); PLG39H7695 (Paraquat) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171103 [Lr] Data última revisão: 171103 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160925 [St] Status: MEDLINE [do] DOI: 10.1007/s11356-016-7681-2

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[PMID]: 28156162 [Au] Autor: Rashed HM; Shamma RN; Basalious EB [Ad] Endereço: a Department of Labeled Compounds , Hot Labs. Center, Egyptian Atomic Energy Authority , Cairo , Egypt and. [Ti] Título: Contribution of both olfactory and systemic pathways for brain targeting of nimodipine-loaded lipo-pluronics micelles: in vitro characterization and in vivo biodistribution study after intranasal and intravenous delivery. [So] Source: Drug Deliv;24(1):181-187, 2016 Nov. [Is] ISSN: 1521-0464 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Nimodipine (NM) is the only FDA-approved drug for treating subarachnoid hemorrhage induced vasospasm. NM has poor oral bioavailability (5-13%) due to its low aqueous solubility, and extensive first pass metabolism. The objective of this study is to develop radiolabeled NM-loaded LPM and to test its ability prolong its circulation time, reduce its frequency of administration and eventually target it to the brain tissue. NM was radiolabeled with Tc by direct labeling method using sodium dithionite. Different reaction conditions that affect the radiolabeling yield were studied. The in vivo pharmacokinetic behavior of the optimum NM-loaded LPM formulation in blood, heart, and brain tissue was compared with NM solution, after intravenous and intranasal administration. Results show that the radioactivity percentage (%ID/g) in the heart of mice following administration of Tc-NM loaded LPM were lower compared with that following administration of Tc-NM solution, which is greatly beneficial to minimize the cardiovascular side effects. Results also show that the %ID/g in the blood, and brain following intravenous administration of Tc-NM-loaded LPM were higher at all sampling intervals compared with that following intravenous administration of Tc-NM solution. This would be greatly beneficial for the treatment of neurovascular diseases. The drug-targeting efficiency of NM to the brain after intranasal administration was calculated to be 1872.82%. The significant increase in drug solubility, enhanced drug absorption and the long circulation time of the NM-loaded LPM could be promising to improve nasal and parenteral delivery of NM. [Mh] Termos MeSH primário: Bloqueadores dos Canais de Cálcio/administração & dosagem Portadores de Fármacos/administração & dosagem Excipientes/administração & dosagem Nimodipino/administração & dosagem Fosfatidilcolinas/administração & dosagem Poloxâmero/administração & dosagem Vasodilatadores/administração & dosagem [Mh] Termos MeSH secundário: Administração Intranasal Animais Disponibilidade Biológica Barreira Hematoencefálica/metabolismo Bloqueadores dos Canais de Cálcio/sangue Bloqueadores dos Canais de Cálcio/metabolismo Bloqueadores dos Canais de Cálcio/farmacocinética Portadores de Fármacos/metabolismo Portadores de Fármacos/farmacocinética Composição de Medicamentos Excipientes/química Meia-Vida Injeções Intravenosas Camundongos Micelas Nanotecnologia Nimodipino/sangue Nimodipino/metabolismo Nimodipino/farmacocinética Tamanho da Partícula Fosfatidilcolinas/química Poloxaleno/administração & dosagem Poloxaleno/química Poloxâmero/química Solubilidade Tecnécio Distribuição Tecidual Vasodilatadores/sangue Vasodilatadores/metabolismo Vasodilatadores/farmacocinética [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Calcium Channel Blockers); 0 (Drug Carriers); 0 (Excipients); 0 (Micelles); 0 (Phosphatidylcholines); 0 (Vasodilator Agents); 0 (pluronic block copolymer P123); 106392-12-5 (Poloxamer); 57WA9QZ5WH (Nimodipine); 7440-26-8 (Technetium); 9003-11-6 (Poloxalene) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 170223 [Lr] Data última revisão: 170223 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170204 [St] Status: MEDLINE [do] DOI: 10.1080/10717544.2016.1236848

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[PMID]: 27374195 [Au] Autor: Russo A; Pellosi DS; Pagliara V; Milone MR; Pucci B; Caetano W; Hioka N; Budillon A; Ungaro F; Russo G; Quaglia F [Ad] Endereço: Laboratory of Biochemistry, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy. [Ti] Título: Biotin-targeted Pluronic(®) P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells. [So] Source: Int J Pharm;511(1):127-139, 2016 Sep 10. [Is] ISSN: 1873-3476 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic(®) P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic(®) F127 was conjugated with biotin, while Pluronic(®) P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein-rich media and improved cytotoxicity in A549 cells as compared to free NCL (P<0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin-decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance. [Mh] Termos MeSH primário: Biotina/administração & dosagem Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos Neoplasias Pulmonares Niclosamida/administração & dosagem Poloxaleno/administração & dosagem Poloxâmero/administração & dosagem [Mh] Termos MeSH secundário: Células A549 Animais Antineoplásicos/administração & dosagem Antineoplásicos/metabolismo Biotina/metabolismo Sobrevivência Celular/efeitos dos fármacos Sobrevivência Celular/fisiologia Relação Dose-Resposta a Droga Sistemas de Liberação de Medicamentos/métodos Resistência a Medicamentos Antineoplásicos/fisiologia Seres Humanos Neoplasias Pulmonares/tratamento farmacológico Neoplasias Pulmonares/metabolismo Camundongos Micelas Células NIH 3T3 Niclosamida/metabolismo Poloxaleno/metabolismo Poloxâmero/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Micelles); 0 (pluronic block copolymer P123); 106392-12-5 (Poloxamer); 6SO6U10H04 (Biotin); 8KK8CQ2K8G (Niclosamide); 9003-11-6 (Poloxalene) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170925 [Lr] Data última revisão: 170925 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160705 [St] Status: MEDLINE

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[PMID]: 27154250 [Au] Autor: Song CK; Yoon IS; Kim DD [Ad] Endereço: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea; Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea. [Ti] Título: Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailability. [So] Source: Int J Pharm;507(1-2):102-8, 2016 Jun 30. [Is] ISSN: 1873-3476 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Development of an oral docetaxel formulation has been hindered mainly due to its poor solubility and oral bioavailability. The aim of this study was to develop poloxamer F68/P85-based solid dispersions (SDs) for the oral delivery of docetaxel and investigate their in vivo pharmacokinetic impacts on the systemic absorption of docetaxel given orally, in comparison with a SD based on F68 alone. The F68 and/or P85-based docetaxel SDs were prepared with varying the contents of poloxamers and then evaluated in terms of morphology, crystallinity, solubility, dissolution, permeation across rat intestinal segments, and oral pharmacokinetics in rats. As a result, the SDs successfully changed the crystalline properties of docetaxel and enhanced the drug solubility and dissolution. The SD prepared with F68 alone significantly enhanced the dissolution but not intestinal permeation of docetaxel, leading to only limited enhancement of oral bioavailability (1.39-fold increase). Notably, however, the F68/P85-based SD significantly enhanced both the dissolution and intestinal permeation of docetaxel, achieving a markedly improved oral bioavailability (2.97-fold increase). Therefore, the present results suggest that the intestinal permeation factor should be taken into account when designing SD formulations for the oral delivery of BCS class IV drugs including docetaxel, and that P85 could serve as a potential formulation excipient for enhancing the intestinal permeation of docetaxel. [Mh] Termos MeSH primário: Poloxaleno/administração & dosagem Poloxaleno/química Poloxâmero/administração & dosagem Poloxâmero/química Taxoides/administração & dosagem Taxoides/farmacocinética [Mh] Termos MeSH secundário: Administração Oral Animais Disponibilidade Biológica Cristalização Liberação Controlada de Fármacos Intestinos/metabolismo Masculino Ratos Solubilidade Taxoides/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Taxoids); 0 (pluronic block copolymer p85); 106392-12-5 (Poloxamer); 15H5577CQD (docetaxel); 9003-11-6 (Poloxalene) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170718 [Lr] Data última revisão: 170718 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160508 [St] Status: MEDLINE

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