RESUMEN
Colorectal cancer (CRC) is the third most prominent cancer worldwide, and the second leading cause of cancer death. Poor outcomes and limitations of current treatments fuel the search for new therapeutic options. Curcumin (CUR) is often presented as a safer alternative for cancer treatment with a staggering number of molecular targets involved in tumor initiation, promotion, and progression. Despite being promising, its therapeutic potential is hindered due to its hydrophobic nature. Hence, the ongoing development of optimal delivery strategies based on nanotechnology, such as polymeric micelles (PMs), to overcome issues in CUR solubilization and delivery to tumor cells. In this sense, this study aimed to optimize the development and stability of CUR-loaded P123:F127:TPGS PMs (PFT:CUR) based on the thin-film approach and evaluate their therapeutic potential in CRC. Overall, the results revealed that the solubility of CUR was improved when room temperature was used to hydrate the film. The PFT-CUR hydrated at room temperature presents an average hydrodynamic diameter of 15.9 ± 0.3 nm with a polydispersity index (PDI) of 0.251 ± 0.103 and a zeta potential of -1.5 ± 1.9 mV, and a 35.083 ± 1.144 encapsulation efficiency (EE%) and 3.217 ± 0.091 drug loading (DL%) were observed. To ensure the stability of the optimized PFT-CUR nanosystems, different lyophilization protocols were tested, the use of 1% of glycine (GLY) being the most promising protocol. Regarding the critical micellar concentration (CMC), it was shown that the cryoprotectant and the lyophilization process could impact it, with an increase from 0.064 mg/mL to 0.119 mg/mL. In vitro results showed greater cytotoxic effects when CUR was encapsulated compared to its free form, yet further analysis revealed the heightened cytotoxicity could be attributed to the system itself. Despite challenges, the developed CUR-loaded PM shows potential as an effective therapeutic agent for CRC. Nonetheless, the system must undergo refinements to enhance drug entrapment as well as improve overall stability.
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Neoplasias Colorrectales , Curcumina , Micelas , Vitamina E , Curcumina/química , Curcumina/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Humanos , Vitamina E/química , Portadores de Fármacos/química , Poloxaleno/química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Solubilidad , Polímeros/química , Liberación de FármacosRESUMEN
Lyotropic liquid crystals (LLCs) have attracted considerably growing interest in drug delivery applications over the last years. The structure of LLC matrices is complementary to cell membranes and provides an efficient, controlled, and selective release of drugs. In this work, a complex of experimental methods was used to characterize binary LLCs Pluronic P123/DMSO and triple LLC systems Pluronic P123/DMSO/Ibuprofen, which are interesting as transdermal drug delivery systems. Liquid crystalline, thermal, and rheological properties of LLCs were studied. Concentration and temperature areas of the lyomesophase existence were found, and phase transition enthalpies were evaluated. Intermolecular interactions among the components were studied by infrared (IR) spectroscopy. In vitro studies of Ibuprofen (Ibu) release from various LLCs allow differentiation of its release depending on the polymer content. Atomic force microscopy and contact angle methods were used to characterize the surface morphology of the hydrophobic membrane, which was used as a stratum corneum model, and also evaluate the adhesion work of the LLCs. A complex analysis of the results provided by these experimental methods allowed revealing correlations between the phase behavior and rheological characteristics of the LLCs and release kinetics of ibuprofen. The proposed biocompatible systems have considerable potential for a transdermal delivery of bioactive substances.
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Ibuprofeno , Cristales Líquidos , Poloxaleno , Cristales Líquidos/química , Ibuprofeno/química , Ibuprofeno/administración & dosificación , Poloxaleno/química , Reología , Administración Tópica , Liberación de FármacosRESUMEN
Purpose: Numerous failures in melanoma treatment as a highly aggressive form of skin cancer with an unfavorable prognosis and excessive resistance to conventional therapies are prompting an urgent search for more effective therapeutic tools. Consequently, to increase the treatment efficiency and to reduce the side effects of traditional administration ways, herein, it has become crucial to combine photodynamic therapy as a promising therapeutic approach with the selectivity and biocompatibility of a novel colloidal transdermal nanoplatform for effective delivery of hybrid cargo with synergistic effects on melanoma cells. Methods: The self-assembled bilosomes, co-stabilized with L-α-phosphatidylcholine, sodium cholate, Pluronic® P123, and cholesterol, were designated, and the stability of colloidal vesicles was studied using dynamic and electrophoretic light scattering, also provided in cell culture medium (Dulbecco's Modified Eagle's Medium). The hybrid compounds - a classical photosensitizer (Methylene Blue) along with a complementary natural polyphenolic agent (curcumin), were successfully co-loaded, as confirmed by UV-Vis, ATR-FTIR, and fluorescent spectroscopies. The biocompatibility and usefulness of the polymer functionalized bilosome with loaded double cargo were demonstrated in vitro cyto- and phototoxicity experiments using normal keratinocytes and melanoma cancer cells. Results: The in vitro bioimaging and immunofluorescence study upon human skin epithelial (A375) and malignant (Me45) melanoma cell lines established the protective effect of the PEGylated bilosome surface. This effect was confirmed in cytotoxicity experiments, also determined on human cutaneous (HaCaT) keratinocytes. The flow cytometry experiments indicated the enhanced uptake of the encapsulated hybrid cargo compared to the non-loaded MB and CUR molecules, as well as a selectivity of the obtained nanocarriers upon tumor cell lines. The phyto-photodynamic action provided 24h-post irradiation revealed a more significant influence of the nanoplatform on Me45 cells in contrast to the A375 cell line, causing the cell viability rate below 20% of the control. Conclusion: As a result, we established an innovative and effective strategy for potential metastatic melanoma treatment through the synergism of phyto-photodynamic therapy and novel bilosomal-origin nanophotosensitizers.
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Curcumina , Melanoma , Nanomedicina , Fotoquimioterapia , Fármacos Fotosensibilizantes , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Fotoquimioterapia/métodos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/administración & dosificación , Curcumina/química , Curcumina/farmacología , Supervivencia Celular/efectos de los fármacos , Liposomas/química , Liposomas/farmacología , Colesterol/química , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacología , Colato de Sodio/química , Sistemas de Liberación de Medicamentos/métodos , Poloxaleno/química , Poloxaleno/farmacologíaRESUMEN
Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.
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Antineoplásicos , Neoplasias Óseas , Neoplasias de la Mama , Poloxaleno , Humanos , Femenino , Micelas , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ligandos , Calidad de Vida , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Polímeros/química , Polímeros/uso terapéutico , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias Óseas/tratamiento farmacológico , Alendronato/farmacología , Alendronato/química , Alendronato/uso terapéutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéuticoRESUMEN
Salicylic acid (SA) finds extensive applications in the treatment of rheumatic and skin diseases because of its analgesic, anti-inflammatory and exfoliating properties. As it is lipophilic in nature, there is a need for appropriate delivery systems to harness these properties for different applications. Herein, we examined the suitability of Pluronic P123/F127 micellar systems as delivery media by investigating the structural, flow and antimicrobial properties of P123/F127-SA solutions and hydrogels using DLS, SANS, rheological and zone inhibition measurement techniques. SA modulates the aggregation characteristics of these surfactant systems and brings about spherical-to-worm-like micelle-to-vesicular structural transitions in the hydrophobic Pluronic P123 system, a spherical-to-worm-like micellar transition in the mixed P123/F127 system and an onset of inter-micellar attraction in the hydrophilic Pluronic F127 system. SA-solubilized systems of both hydrophobic and hydrophilic Pluronics inhibit the growth of Gram-positive and Gram-negative bacteria with comparable MIC values. This suggests that the interaction of SA molecules with the bacterial cell membrane remains unobstructed upon encapsulation in Pluronic micelles. F127 hydrogel-based SA formulations with rheological properties suitable for topical applications and up to 15% SA loading were prepared. These will be useful SA ointments as F127 is an FDA-approved excipient for topical drug delivery applications. The results indicate that Pluronics remain effective as delivery agents for SA and exhibit interesting structural polymorphism upon its solubilization.
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Hidrogeles , Poloxaleno , Poloxámero , Polietilenos , Polipropilenos , Poloxámero/química , Ácido Salicílico/farmacología , Antibacterianos , Bacterias Gramnegativas , Bacterias Grampositivas , MicelasRESUMEN
The objective of this study was to develop folic acid (FA) grafted mixed polymeric micelles loaded with Tamoxifen citrate (TMXC) to enhance its antitumor activity in breast tissues. The conjugated folic acid Pluronic 123 (FA-P123) was prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. TMXC-loaded P123/P84 (unconjugated) and TMXC-loaded FA-P123/P84 (conjugated) micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro drug release, cytotoxic effect, and cellular uptake by a breast cancer cell line. The conjugated TMXC-loaded micelle exhibited a nanoparticle size of 35.01 ± 1.20 nm, a surface charge of-20.50 ± 0.95 mV, entrapped 87.83 ± 5.10% and released 67.58 ± 2.47% of TMXC after 36 h. The conjugated micelles exhibited a significantly higher cellular uptake of TMXC by the MCF-7 cell line and improved in vitro cytotoxicity by 2.48 folds compared to the TMXC-loaded unconjugated micelles. The results of in vivo studies indicated that TMXC-loaded FA-P123/P84 has a potential antitumor activity, as revealed by a significant reduction of tumor volume in tumor-bearing mice compared to TMXC-loaded unconjugated micelles. In conclusion, the obtained results suggested that conjugated FA-P123/P84 micelles could be an encouraging carrier for the treatment of breast cancer with TMXC.
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Micelas , Neoplasias , Ratones , Animales , Tamoxifeno , Ácido Fólico/química , Poloxaleno/química , Línea Celular Tumoral , Polímeros/química , Portadores de Fármacos/químicaRESUMEN
Polyurethane (PU) and poly(l-lactide) (PLLA) have attracted increasing attention in the development of shape memory polymers (SMPs) due to their good biocompatibility and degradability. Although Pluronic P123 can be used to tune polymeric surface hydrophilicity, its effect on SM performance is a mystery. In this study, a soluble cross-linked PU is synthesized as the switching phase and combined with PLLA and P123 to construct a hydrothermally responsive SM composite. The water contact angle of PU/PLLA/P123 decreases from 22.7° to 5.1° within 2 min. PU and P123 form the switching group, which enhances the SM behavior of the composite. The shape fixity (Rf) and shape recovery (Rr) of PU/PLLA/P123 are 94.4 % and 98 % in 55 °C water, respectively, and the shape recovery time is only 10 s. P123 plays the role of "turbine" in the SM process. PU/PLLA/P123 exhibits a balance between stiffness and elasticity, and good degradability. Furthermore, PU/PLLA/P123 is also biocompatible and beneficial to cell proliferation and growth. Therefore, it offers an alternative approach to developing hydrothermally responsive SM biocomposites based on P123, PU and PLLA for biomedical applications.
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Poloxaleno , Poliuretanos , Poliésteres , Agua , Materiales BiocompatiblesRESUMEN
The poultry industry in developing countries is still combating mortality and economic loss due to Salmonella contamination. Salmonella Gallinarum is a common pathogen of poultry birds, being the etiologic agent of fowl typhoid, which specifically infects adult birds via the oral-fecal route. Timely detection of S. Gallinarum in poultry flocks can allow early treatment intervention leading to a decrease in economic losses. Detection of S. Gallinarum is challenging, while its PCR-based detection is a promising strategy, however, due to its high genomic similarity with other commonly existing Salmonella spp., identification of S. Gallinarum from poultry samples with high specificity is still a challenge. The current study was conducted to isolate S. Gallinarum from different districts of Pakistan, assess their antibiotic susceptibility profile, and develop a method for its early detection. A total of 20 strains were isolated using buffer peptone water, selenite cysteine broth, and Xylose Lysine Tergitol-4 (XLT-4) agar supplemented with tergitol and characterized by biochemical procedures. The antibiotic sensitivity profile highlighted the highest resistance of isolates towards novobiocin and nalidixic acid, commonly used antibiotics in Pakistan Poultry production. The primers designed to amplify a unique genomic region of S. Gallinarum, showed successful detection of twenty S. Gallinarum strains, while no amplification with genomic DNA from other common Salmonella spp. The reported method can be utilized to detect S. Gallinarum from tissue samples of infected birds in a short time leading to early diagnosis and timely treatment intervention.
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Enfermedades de las Aves de Corral , Salmonelosis Animal , Animales , Aves de Corral , Pakistán , Poloxaleno , Enfermedades de las Aves de Corral/diagnóstico , Salmonella/genética , Aves , Reacción en Cadena de la Polimerasa/veterinaria , Farmacorresistencia Microbiana , Antibacterianos/farmacología , Diagnóstico Precoz , Salmonelosis Animal/diagnóstico , PollosRESUMEN
OBJECTIVES: The triblock copolymer Pluronic® is widely used in the personal care industry, including sun protection, for its film-forming and solubilization capabilities. In this study, the effect of three commonly used organic UV filters (ethylhexyl methoxycinnamate [EMC], ethylhexyl triazone [EHT], and avobenzone [AVB]) on the structure of Pluronic P123 micelles was investigated. METHODS: The Pluronic P123 micelle structure has been investigated using dynamic surface tension, nuclear magnetic resonance (NMR) and small-angle neutron scattering (SANS). RESULTS: Dynamic surface tension results show strong interactions between the UV filters and Pluronic® evident by sharp changes in the surface activity of the latter. The NMR results have revealed the creation of a hydrophobic microenvironment special to the Pluronic PPO core group in the presence of UV filters. Some interaction with the hydrophilic EO was also recorded, albeit weaker. This is further confirmed by SANS, where the Pluronic P123 micelles interacted with varying strengths with the UV filters, resulting in sharp changes in their size and shape. CONCLUSIONS: We have demonstrated the sensitivity of the Pluronic P123 micelles to the presence of various UVA/B filters. The micelles shape varied from spherical to cylindrical as the concentration and type of the UV filters were varied. These variations in the shape are expected to have a significant effect on the sun protection factor (SPF), as it affects the solubilization of the UV filters within a formulation in addition to the formulations' rheological profile and film-forming behaviour.
OBJECTIFS: le copolymère tribloc Pluronic® est largement utilisé dans le domaine des soins personnels, notamment la protection solaire, pour ses capacités de formation de film et de solubilisation. Cette étude a permis d'étudier l'effet de trois filtres UV organiques couramment utilisés (éthylhexyl méthoxycinnamate [EMC], éthylhexyl triazone [EHT] et avobenzone [AVB]) sur la structure des micelles P123 Pluronic. MÉTHODES: la structure de la micelle P123 Pluronic a été étudiée à l'aide d'une tension superficielle dynamique, d'une résonance magnétique nucléaire (RMN) et d'une diffusion de neutrons aux petits angles (DNPA). RÉSULTATS: les résultats de la tension superficielle dynamique montrent de fortes interactions entre les filtres UV et Pluronic®, ce qui se traduit par de fortes variations de l'activité superficielle de ce dernier. Les résultats de la RMN ont montré la création d'un micro-environnement hydrophobe spécifique au groupe principal de l'OPP pluronique en présence de filtres UV. Une certaine interaction avec l'OE hydrophile a également été enregistrée, quoique plus faible. Ceci est confirmé par la DNPA, où les micelles P123 Pluronic ont interagi avec des forces variables avec les filtres UV, entraînant des changements importants dans leur taille et leur forme. CONCLUSIONS: nous avons démontré la sensibilité des micelles P123 Pluronic à la présence de différents filtres UVA/B. La forme des micelles variait de sphérique à cylindrique en fonction de la concentration et du type de filtres UV. Ces variations de forme devraient avoir un effet significatif sur le facteur de protection solaire (SPF), car elles affectent la solubilisation des filtres UV dans une formulation, en plus du profil rhéologique et du comportement de formation de film des formulations.
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Micelas , Poloxámero , Poloxámero/química , Protectores Solares , Poloxaleno/químicaRESUMEN
Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug-resistant bacteria. Here, an in situ-formed biotherapeutic gel that controls multidrug-resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene-polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities-based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria-derived xenograft infection models, as well as in patient-derived multidrug-resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad-spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug-resistant bacterial infections.
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Antiinfecciosos , Infecciones Bacterianas , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Poloxaleno/farmacología , Infecciones Bacterianas/tratamiento farmacológicoRESUMEN
Multifunctional P123 micelle linked covalently with spermine (SM) and folic acid (FA) was developed as a drug delivery system of hypericin (HYP). The chemical structures of the modified copolymers were confirmed by spectroscopy and spectrophotometric techniques (UV-vis, FTIR, and 1H NMR). The copolymeric micelles loading HYP were prepared by solid dispersion and characterized by UV-vis, fluorescence, dynamic light scattering (DLS), ζ potential, and transmission electron microscopy (TEM). The results provided a good level of stability for HYP-loaded P123-SM, P123-FA, and P123-SM/P123-FA in the aqueous medium. The morphology analysis showed that all copolymeric micelles are spherical. Well-defined regions of different contrast allow us to infer that SM and FA were localized on the surface of micelles, and the HYP molecules are located in the core region of micelles. The uptake potential of multifunctional P123 micelle was accessed by exposing the micellar systems loading HYP to two cell lines, B16-F10 and HaCaT. HYP-loaded P123 micelles reveal a low selectivity for melanoma cells, showing significant photodamage for HaCat cells. However, the exposition of B16-F10 cells to Hyp-loaded SM- and FA-functionalized P123 micelles under light irradiation revealed the lowest CC50 values. The interpretation of these results suggested that the combination of SM and FA on P123 micelles is the main factor in enhancing the HYP uptake by melanoma cells, consequently leading to its photoinactivation.
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Melanoma , Fotoquimioterapia , Humanos , Micelas , Fotoquimioterapia/métodos , Ácido Fólico/química , Poloxaleno/química , Espermina , Polímeros/química , Melanoma/tratamiento farmacológico , Portadores de Fármacos/químicaRESUMEN
The potential for liquid biopsy samples to be used in place of more invasive tissue biopsies has become increasingly revalent as it has been found that nucleic acids (NAs) present in the blood of cancer patients originate from tumors. Nanomagnetic extraction has proven to be a highly effective means to rapidly prepare NA from clinical samples for molecular diagnostics. In this article, the lysis reaction used to extract RNA from the human epithelial melanoma cells have been optimized using silica coated superparamagnetic nanoparticles (SPM NP). The lysis buffer (LB) is composed of several agents that denature cells, i.e., surfactant and guanidinium isothiocyanate (GITC), and agents that inhibit the degradation of circulated nucleic acids (cfNAs). The surfactant Triton X-100 has been widely used in LB but has been placed on the European Union REACH list. We have compared the qRT-PCR sensitivity resulting from LBs composed of Triton X-100 to several sustainable surfactants, i.e., Tergitol 15-S-7, Tergitol 15-S-9 and Tween-20. Surprisingly, the inclusion of these surfactants in the LB was not found to significantly improve cell lysis, and subsequently the sensitivity of qRT-PCR. The role of the sample matrix was also examined by performing extractions from solutions containing up to 30 mg mL-1 serum albumin. The qRT-PCR sensitivity was found to decrease as the concentration of this protein was increased; however, this was linked to an increased RNase activity and not the concentration of the protein itself. These results lead us to recommend a reformulation of LB for clinical samples, and to conclude that sensitive qRT-PCR RNA analysis can be performed in serum with the timely addition of an RNase inhibitor.
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Detergentes , Ácidos Nucleicos , ARN , Ribonucleasas , Células Eucariotas , Humanos , Melanoma , Octoxinol , Poloxaleno , ARN/aislamiento & purificación , Ribonucleasas/antagonistas & inhibidoresRESUMEN
Residual oil in palm oil mill effluent (POME) poses difficulties in its treatment chain. Non-ionic surfactants containing different hydrophobic tail structures and their optimal concentrations were evaluated for effectiveness in biohydrogen production. By adding the surfactants at their critical micelle concentration in synthetic oily wastewater, the maximal H2 yield was increased by 2.2 and 3.5 times for Triton X-100 and Tergitol 15-S-9, respectively, compared to the control. Using real POME, the supplemental Tergitol 15-S-9 resulted in a 56.4 % improvement in H2 production. For continuous digestion studies, pure POME and Tergitol 15-S-9 supplemented POME (sPOME) were fed to thermophilic anaerobic sequencing batch reactors (ASBRs) under hydraulic retention time (HRT) of 32-12.5 days. Optimally at HRT 19 days, H2 content in the biogas from sPOME-fed ASBR was noticeably higher, which gave a superior yield of 203.4 mLH2/gCODremoved (+15 %).
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Reactores Biológicos , Aguas Residuales , Anaerobiosis , Fermentación , Aceite de Palma , Poloxaleno , TensoactivosRESUMEN
The hydrophobicity of most of the anticancer drugs offers a great challenge in selecting a system for their effective transport. Here comes the importance of micelles that offers a hydrophobic core for incorporating these drugs. In this study, Hyaluronic Acid coated Pluronic mixed micelle loaded with Paclitaxel and Curcumin was designed and evaluated its anticancer activity in MCF-7 cells. Pluronic F127 (PF127) and Pluronic P123 (PP123) were taken for preparing the mixed micelles. The targeting ligand folic acid (FA) was conjugated to one end of PP123 forming FA-PP. The end hydroxyl groups of PF127 were oxidized to aldehyde groups resulted in PF-CHO. Mixed micelles were prepared from PF-CHO and FA-PP and the end aldehyde groups were used for coating the micelles with hyaluronic acid. The material was characterized using FTIR, H1NMR, DLS, FE-SEM and TEM. The coated micelles showed spherical shape with drug loading efficiency of 50.15 and 65.05% for Paclitaxel and Curcumin, respectively. In vitro drug release was studied at pH 5.5 and 7.4. Dual drug-loaded material showed higher in-vitro anticancer activity than free Paclitaxel and Curcumin. The results suggested that synthesized mixed micelle with dual drugs showed great potential for targeted delivery to MCF-7 cells.
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Materiales Biocompatibles Revestidos , Curcumina/administración & dosificación , Portadores de Fármacos/química , Ácido Hialurónico/química , Micelas , Paclitaxel/administración & dosificación , Poloxaleno/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Curcumina/farmacología , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Paclitaxel/química , Paclitaxel/farmacología , Tamaño de la Partícula , Análisis EspectralRESUMEN
Inactivation of SARS-CoV-2 virus is necessary to mitigate risk but may interfere with diagnostic assay performance. We examined the effect of heat inactivation on a prototype SARS-CoV-2 antigen immunoassay run on the ARCHITECT automated analyzer. Recombinant full-length SARS-CoV-2 nucleocapsid protein and virus lysate detection was reduced by 66 and 31%, respectively. Several nonionic detergents were assessed as inactivation alternatives based on infectivity in cultured Vero CCL81 cells. Incubation of SARS-CoV-2 in 0.1% Tergitol 15-S-9 for 10 min significantly reduced infectivity and increased the immunoassay signal for cultured lysate and patient specimens. Tergitol 15-S-9 can inactivate SARS-CoV-2 while preserving epitopes on the nucleocapsid protein for enhanced detection by immunoassay antibodies.
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Prueba de COVID-19/métodos , Poloxaleno/farmacología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , Inactivación de Virus/efectos de los fármacos , Animales , Anticuerpos Antivirales/efectos de los fármacos , Anticuerpos Antivirales/inmunología , COVID-19/diagnóstico , COVID-19/inmunología , Prueba de COVID-19/normas , Células Cultivadas , Chlorocebus aethiops , Humanos , Inmunoensayo/métodos , Inmunoensayo/normas , Nucleocápside/inmunología , Tensoactivos/farmacología , Células VeroRESUMEN
BACKGROUND: Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. RESULTS: Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. CONCLUSIONS: These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. GRAPHIC ABSTARCT.
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Antineoplásicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Micelas , Mitocondrias/metabolismo , Nanopartículas/química , Paclitaxel/metabolismo , Células A549 , Apoptosis , Sistemas de Liberación de Medicamentos/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Mitocondrias/efectos de los fármacos , Membranas Mitocondriales/efectos de los fármacos , Nanopartículas/uso terapéutico , Oxidación-Reducción , Paclitaxel/química , PoloxalenoRESUMEN
The aqueous extract of fallen leaves from Fridericia chica (Bonpl.) L.G. Lohmann is utilized as a remedy in communities at northern Colombia. Traditional uses include wound healing, gastrointestinal inflammation, leukemia and psoriasis, among others. The aims of this research were to evaluate the potential of the aqueous extract of fallen leaves of F. chica (AEFchica) to inhibit ethoxylated nonylphenol (Tergitol)-induced toxicity in Caenorhabditis elegans; and to identify its main components. The pharmacological properties of AEFchica was evaluated using a Tergitol-induced toxicity model in Caenorhabditis elegans. Lethality, locomotion, reproduction, and DAF-16 nuclear translocation were quantified. The chemical composition of AEFchica was carried out using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. AEFchica induced very little lethality on C. elegans (5.6%) even at high concentrations (10,000 µg/mL). The extract had no effect on locomotion impairing induced by ethoxylated nonylphenol. However, AEFchica (1000 µg/mL) abrogated Tergitol-induced mortality, recovering up to 53.3% of the nematodes from lethality induced by 10 mM Tergitol. Similarly, it also blocked Tergitol-dependent reproduction inhibition (82.1% recovery), as well as DAF-16 nuclear translocation (>95%), suggesting a prominent role on oxidative stress control. The chemical analysis indicated the presence of a great variety of molecules with known antioxidant, metabolic and immune modulator properties, such as hydroxylated methoxy flavones, N-methyl-1-deoxynojirimycin, and rehmaionoside A. In short, the aqueous extract of F. chica protects C. elegans from the deleterious effects of Tergitol on lethality, reproduction and oxidative stress involving DAF-16-mediated pathway. This extract is a promising source of bioactive phytochemicals for multi-target pharmacological purposes.
Asunto(s)
Antioxidantes , Bignoniaceae/química , Caenorhabditis elegans/efectos de los fármacos , Extractos Vegetales , Hojas de la Planta/química , Poloxaleno/toxicidad , Animales , Antioxidantes/química , Antioxidantes/farmacología , Colombia , Locomoción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Reproducción/efectos de los fármacosRESUMEN
Drug delivery systems for the sustained and target delivery of doxorubicin to tumor cells are a topic of interest due to the efficacy of the doxorubicin in cancer treatment. The use of polymers such as Pluronic is being studied widely for the formulation of doxorubicin hydrochloride. However, the basic understanding of the physicochemical properties of pluronic micelles in presence of doxorubicin hydrochloride is a very essential topic of study. Doxorubicin hydrochloride is fluorescent; this helped us to study its sensitivity towards the Pluronic microenvironment using the fluorescence technique. In this work, the interaction and place of location of doxorubicin hydrochloride in Pluronic F127 and P123 micelles has been studied extensively using steady-state fluorescence intensity, dynamic fluorescence lifetime, quenching studies, dynamic light scattering, and zeta potential measurements, at different Pluronic concentrations. Using a fluorescence quenching experiment, doxorubicin hydrochloride was found to reside near the hydrophilic PEO corona region of the Pluronic micelles. For both the Pluronic, in the concentration range of study, the micellar size was found to be below 30 nm; this may have a greater advantage for various applications.
Asunto(s)
Antineoplásicos/química , Doxorrubicina/química , Micelas , Poloxaleno/química , Polietilenos/química , Polipropilenos/química , Fluorescencia , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.
Asunto(s)
Antineoplásicos/administración & dosificación , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antracenos , Antineoplásicos/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Femenino , Células HeLa , Humanos , Micelas , Invasividad Neoplásica , Estrés Oxidativo/efectos de los fármacos , Perileno/administración & dosificación , Perileno/farmacología , Poloxaleno/química , Factores de Tiempo , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells. RESULTS: The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1. CONCLUSIONS: P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms. METHODS: The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.