RESUMEN

BACKGROUND: This study aims to evaluate the percutaneous permeation profiles of caffeic acid (CA) from the cubic and hexagonal liquid crystalline phases of Pluronic P123/water mixtures. METHOD: The resulting drug-loaded mesophases were subjected to characterisation through deuterium nuclear magnetic resonance spectroscopy and polarised optical microscopy observations. These analyses aimed to evaluate the structural changes that occurred in the mesophases loading with CA. Additionally, steady and dynamic rheology studies were conducted to further explore their mechanical properties and correlate them to the supramolecular structure. Finally, CA release experiments were carried out at two different temperatures to examine the behaviour of the structured systems in a physiological or hyperthermic state. RESULTS: As the concentration of the polymer increases, an increase in the viscosity of the gel is noted; however, the addition of caffeic acid increases microstructure fluidity. It is observed that the temperature effect conforms to expectations. The increase in temperature causes a decrease in viscosity and, consequently, an increase in the rate of permeation of caffeic acid. CONCLUSIONS: The CA permeation profile from the prepared formulations is mostly dependent on the structural organisation and temperature. Cubic mesophase LLC 30/CA showed greater skin permeation with good accumulation in the skin at both tested temperatures.

RESUMEN

Herein, we report a multifunctional hydrogel membrane with good mechanical properties, excellent antioxidant efficiency, and broad-spectrum antimicrobial activity. For this purpose, a series of chitosan-carboxymethyl cellulose-Pluronic P123 (CHT-CMC-P123) hydrogel membranes were prepared by blending various tetracycline hydrochloride (TCH) contents. The physicochemical and biological properties of CHT-CMC-P123 membranes were comprehensively investigated. With the increase of TCH content from 5 % to 20 %, hydrogel membranes presented a decreased water contact angle from 18.96° to 11.24°, and a decreased water vapor transmission rate from 171.8 to 156.1 g/m2 h. Besides, with the increase of TCH content (5-20 %), the tensile strength (0.31-0.11 MPa) and elongation at break (10.57-4.82 %) of hydrogel membranes decreased while their thickness increased (113.5-324.3 µm). The data show that the release of TCH reached equilibrium after 26 days, with a cumulative percentage of approximately 28 %-87 %. Moreover, the hydrogel membranes exhibited a high antioxidant capacity of ~92 % for DPPH radical. Importantly, the incorporation of TCH significantly (~2.3 fold) enhanced the antimicrobial activity of the hydrogel membranes against Gram-positive, and Gram-negative bacteria and yeast. Based on our findings, these hydrogel membranes with superior properties may serve as effective food packaging and wound healing materials.

Asunto(s)

Antiinfecciosos , Quitosano , Tetraciclina/farmacología , Tetraciclina/química , Quitosano/química , Carboximetilcelulosa de Sodio/química , Hidrogeles/química , Antioxidantes/farmacología , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/química

RESUMEN

The data provided in this study are related to the fabrication of two light-responsive systems based on reduced graphene oxide (rGO) functionalized with the polymers Pluronic P123 (P123), rGO-P123, and polyethyleneimine (PEI), rGO-PEI, and loaded with amphotericin B (AmB), an antileishmanial drug. Here are described the experimental design to obtain the systems and characterization methods, such as Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman Spectroscopy, Powder X-Ray Diffraction, Transmission Electron Microscopy, Scanning Electron Microscopy and Thermogravimetric Analyses. Also, AmB spectroscopy studies are described. The materials rGO-P123 and rGO-PEI were loaded with AmB and the optimization of AmB and polymer fragments structures revealed several possible hydrogen bonds formed between the materials and the drug. The drug release was analyzed with and without Near-Infrared (NIR) light. In the studies conducted under NIR light irradiation for 10 min, an infrared lamp was disposed at 64 cm from the samples and an optical fiber thermometer was employed to measure the temperature variation. Cytotoxicity studies and antiproliferative assays against Leishmania amazonensis promastigotes were evaluated. The complete work data entitled Amphotericin-B-Loaded Polymer-Functionalized Reduced Graphene Oxides for Leishmania amazonensis Chemo-Photothermal Therapy have been published to Colloids and Surfaces B: Bionterfaces (https://doi.org/10.1016/j.colsurfb.2021.112169) [1].

RESUMEN

In this study, we investigated two formulations of chitosan-Pluronic P123 with different folate ligand designation for targeted delivery of Paclitaxel (PTX), in which folic acid (FA) was directly conjugated to chitosan (FA-Cs-P123) or substituted onto P123 (Cs-P123-FA). The results showed that the FA content of Cs-P123-FA was determined at 0.71 wt/wt% which was significantly higher than that of FA-Cs-P123 (0.31 wt/wt%). Two copolymers were low critical gel concentrations (CGC). FA-Cs-P123 and Cs-P123-FA nanogels performed high PTX encapsulation efficiency reaching 95.57 ± 5.51 and 92.51 ± 6.68 wt/wt%, respectively. Transmission electron microscopy (TEM) and zeta potential analysis indicated that the PTX-loaded nanogels were spherically formed around 60 nm in diameter along with positive charge. Furthermore, the PTX release profile was slow and it was controlled by the pH of the medium. In particular, in vitro biocompatibility assays indicated that both FA-Cs-P123 and Cs-P123-FA exhibited good biological compatibility with a human foreskin fibroblast cell line and well uptake efficiency into MCF-7 cancer cells. Cs-P123-FA nanogel significantly enhanced the cytotoxicity of PTX in comparison with FA-Cs-P123. The result indicates that Cs-P123-FA nanogels with a higher decorated FA content perform a better targeting efficiency; therefore, they could have great potential application towards breast cancer treatment.

Asunto(s)

Quitosano , Nanopartículas , Neoplasias , Línea Celular Tumoral , Quitosano/química , Portadores de Fármacos/química , Ácido Fólico/química , Humanos , Ligandos , Células MCF-7 , Nanogeles , Nanopartículas/química , Paclitaxel/química , Paclitaxel/farmacología , Poloxámero

RESUMEN

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 Hidrofílicas

RESUMEN

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/patología

RESUMEN

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.

Asunto(s)

Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Poloxaleno/administración & dosificación , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Micelas

RESUMEN

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic subtype of breast cancer showing non-responsiveness to most available therapeutic options. Therefore, smart therapeutic approaches to selectively transport and target TNBCs are required. Herein, we developed thymoquinone (TQ)-loaded, hyaluronic acid (HA)-conjugated Pluronic® P123 and F127 copolymer nanoparticles (HA-TQ-Nps) as a selective drug-carrying vehicle to deliver anticancer phytochemical TQ to TNBC cells. The mean size of nanoparticles was around 19.3 ± 3.2 nm. and they were stable at room temperature up to 4 months. HA-TQ-Nps were immensely cytotoxic towards TNBC cells but did not show the toxic effect on normal cells. Detailed investigations also demonstrated its pro-apoptotic, anti-metastatic and anti-angiogenic activity. In-depth mechanistic studies highlighted that HA-TQ-Nps retarded cell migration of TNBC cells through up-regulation of microRNA-361 which in turn down-regulated Rac1 and RhoA mediated cell migration and also perturbed the cancer cell migration under the influence of the autocrine effect of VEGF-A. Moreover, HA-TQ-Np-treatment also perturbed tumor-induced vascularization by reducing the secretion of VEGF-A. The anti-metastatic and anti-angiogenic activity of HA-TQ-Nps was found to be evident in both MDA-MB-231 xenograft chick embryos and 4T1-mammary solid tumor model in syngeneic mice. Thus, an innovative targeted nano-therapeutic approach is being established to reduce the tumor burden and inhibit metastasis and angiogenesis simultaneously for better management of TNBC.

Asunto(s)

MicroARNs , Nanopartículas , Neoplasias de la Mama Triple Negativas , Animales , Benzoquinonas , Línea Celular Tumoral , Embrión de Pollo , Humanos , Ácido Hialurónico , Ratones , Poloxámero , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico

RESUMEN

Photoinactivation is a promising technique for Staphylococcus aureus control. This microorganism causes foodborne diseases (DTAs) and forms biofilms that are highly resistant and difficult to eradicate. Thus, the aim of this study was to evaluate the photodynamic activity of hypericin (HYP) in polymeric nanoparticles (Pluronic® P123) against S. aureus planktonic and biofilm cells. Planktonic cells and biofilms of S. aureus (ATCC 25923) were subjected to photoinactivation using low-power orange LED (0.3 mW/cm²) with different HYP formulation concentrations in Pluronic® P123. The P123 molar ratios were 2.5 (HYP/P123-2.5) and 10 (HYP/P123-10), respectively. The treatment times for planktonic cells were proposed by a mixture design, and bacterial photoinactivation was observed in concentrations of 12.5 to 3.12 µmol/L for HYP/P123-2.5 and reductions of ∼ 4.0 log CFU/mL in 12.5 to 0.78 µmol/L for HYP/P123-10. For biofilms, 30 min of darkness and 30 min of illumination were used. Maximum reductions were similar for both formulations and corresponded to approximately 0.9 log CFU/cm². It was concluded that photoinactivation with longer lighting times was effective against planktonic cells and could be potentially applied to control S. aureus.

Asunto(s)

Nanopartículas , Fotoquimioterapia , Antracenos , Biopelículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Staphylococcus aureus

RESUMEN

BACKGROUND: Breast cancer is the most relevant type of cancer and the second cause of cancer- related deaths among women in general. Currently, there is no effective treatment for breast cancer although advances in its initial diagnosis and treatment are available. Therefore, the value of novel anti-tumor therapeutic modalities remains an immediate unmet need in clinical practice. Following our previous work regarding the properties of the Pluronics with different photosensitizers (PS) for photodynamic therapy (PDT), in this study we aimed to evaluate the efficacy of supersaturated hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) against breast cancer cells (MCF-7) and non-tumorigenic breast cells (MCF-10A). METHODS: Cell internalization and subcellular distribution of HYP/P123 was confirmed by fluorescence microscopy. The phototoxicity and citototoxicity of HYP/P123 was assessed by trypan blue exclusion assay in the presence and absence of light. Long-term cytotoxicity was performed by clonogenic assay. Cell migration was determined by the wound-healing assay. Apoptosis and necrosis assays were performed by annexin VFITC/ propidium Iodide (PI) by fluorescence microscopy. RESULTS: Our results showed that HYP/P123 micelles had high stability and high rates of binding to cells, which resulted in the selective internalization in MCF-7, indicating their potential to permeate the membrane of these cells. Moreover, HYP/P123 micelles accumulated in mitochondria and endoplasmic reticulum organelles, resulting in the photodynamic cell death by necrosis. Additionally, HYP/P123 micelles showed effective and selective time- and dose dependent phototoxic effects on MCF-7 cells but little damage to MCF-10A cells. HYP/P123 micelles inhibited the generation of cellular colonies, indicating a possible capability to prevent the recurrence of breast cancer. We also demonstrated that HYP/P123 micelles inhibit the migration of tumor cells, possibly by decreasing their ability to form metastases. CONCLUSION: Taken together, the results presented here indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat human breast cancers through photodynamic therapy, suggesting they are worthy for in vivo preclinical evaluations.

Asunto(s)

Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Perileno/análogos & derivados , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Poloxaleno/farmacología , Antracenos , Antineoplásicos/química , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Micelas , Estructura Molecular , Perileno/química , Perileno/farmacología , Fármacos Fotosensibilizantes/química , Poloxaleno/química , Relación Estructura-Actividad

RESUMEN

Laccases are multi-copper oxidase enzymes having widespread applications in various biotechnological fields. However, low stability of free enzymes restricts their industrial use. Development of effective methods to preserve and even increase the enzymatic activity is critical to maximize their use, though this remains a challenge. In the present study we immobilized Trametes versicolor laccase on pH-responsive (and charge-switchable) Pluronic-stabilized silver nanoparticles (AgNPsTrp). Our results demonstrate that colloidal stabilization of AgNPsTrp with the amphiphilic copolymer Pluronic F127 enhances enzyme activity (AgNPsTrpF1 + Lac6) by changing the active site microenvironment, which is confirmed by circular dichroism (CD) and fluorescence spectroscopy. Detailed kinetic and thermodynamic studies reveal a facile strategy to improve the protein quality by lowering the activation energy and expanding the temperature window for substrate hydrolysis. The immobilized nanocomposite did not show any change in flow behavior which indirectly suggests that the enzyme stability is maintained, and the enzyme did not aggregate or unfold upon immobilization. Finally, assessing the anticancer efficacy of this nanocomposite in breast cancer MCF-7 cells shows the inhibition of cell proliferation through ß-estradiol degradation and cells apoptosis. To understand the molecular mechanism involved in this process, semi qRT-PCR experiments were performed, which indicated significant decrease in the mRNA levels of anti-apoptotic genes, for example, BCL-2 and NF-kß, and increase in the mRNA level of pro-apoptotic genes like p53 in treated cells, compared to control. Overall, this study offers a completely new strategy for tailoring nano-bio-interfaces with improved activity and stability of laccase.

Asunto(s)

Neoplasias de la Mama , Enzimas Inmovilizadas , Proteínas Fúngicas , Lacasa , Poloxámero , Polyporaceae/enzimología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Estabilidad de Enzimas , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/farmacología , Femenino , Proteínas Fúngicas/química , Proteínas Fúngicas/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lacasa/química , Lacasa/farmacología , Células MCF-7 , Proteínas de Neoplasias/biosíntesis , Poloxámero/química , Poloxámero/farmacología

RESUMEN

It is well-known that drugs administered into an organism intravenously or through the gastrointestinal tract are degraded by enzymes of the body, reducing their therapeutic effect. One of the ways to decrease this undesirable process is through the inclusion of drugs in nanomaterials. Earlier strong anticoagulant activity was demonstrated for dipeptide IleTrp (IW) and adenosine (Ado). In this work, the effect of inclusion in nanomaterials on the biological activity of IW and Ado was studied. For this purpose, Ado and IW were incorporated into thermosensitive nanogel composed of pluronic P123-grafted heparin. The prepared nanocarrier was characterized by transmission electron microscopy, dynamic light scattering, and ζ-potential. Biological activity was determined by measuring the bleeding time from mouse tail in vivo and the time of clot formation in vitro. It was found that encapsulation of Ado and IW into nanomaterial significantly increased their effects, resulting in an increase in the bleeding time from mouse tail and clot formation time. Thus, inclusion of low molecular weight anticoagulants Ado and IW into nanomaterials may be considered a way to increase their biological activity.

RESUMEN

This study aimed to fabricate the potential therapeutic scaffold to efficiently and safely fastening skin wound healing. A biocompatible grafting polymer-based thermal sensitive hybrid hydrogel (Chitosan-P123, CP) containing gelatin and curcumin was designed to be suitable stiffness for tissue regeneration. A detailed in the rheological study found that the encapsulated agents induced the change in the stiffness of the hydrogel from the hard to the soft. Especial, the thermally induced phase transition of CP hydrogel was governed by the participant of gelatin rather than curcumin. For example, at 25 wt% gelatin, CP hydrogel exhibited a unique gel-sol-gel transition following the function of temperature. Moreover, in vitro investigation revealed that the hybrid hydrogel provides the capacity of especially induced curcumin release with a sustainable rate as well as the excellent biocompatibility scaffold. Altogether with in vivo study, the hybrid hydrogel highlighted the advance of the dual synergistic of curcumin and gelatin in development of smart scaffold system, which promoted the efficacy in the regeneration of the structure and the barrier's function of damaged skin such as wound or skin cancer.

Asunto(s)

Quitosano/química , Curcumina/farmacología , Gelatina/farmacología , Hidrogeles/farmacología , Temperatura , Cicatrización de Heridas/efectos de los fármacos , Animales , Células Cultivadas , Liberación de Fármacos , Sinergismo Farmacológico , Humanos , Masculino , Ratones , Nanopartículas/química , Transición de Fase , Polímeros/síntesis química , Polímeros/química , Espectroscopía de Protones por Resonancia Magnética , Termogravimetría

RESUMEN

Currently marketed drug-eluting stents are non-selective in their anti-restenotic action. New active substance introduction to polymeric stents and vascular grafts can promote early re-endothelialization, crucial in preventing implant restenosis. Additionally, managing material hydrophobicity by blending synthetic polymers limits adverse effects on bulk properties and controls active substance release. However, the influence of hydrophilic synthetic polymer on human cells in the cardiovascular system remains to be determined. In this report, effects of both poly(ε-caprolactone) (PCL) fibers hydrophilization with Pluronic P123 (P123) and cilostazol (CIL) loading were studied. Physicochemical and mechanical properties of electrospun tubular structures produced from PCL and PCL/P123 fibers with and without CIL were investigated and compared. Release profiles studies and in vitro cell proliferation assays of electrospun materials were conducted. It was found that P123 located near the surface of electrospun fibers increased the rate of CIL release. PCL formulation sustained human umbilical vein endothelial cells (HUVEC) growth for 48 h. Despite improved hydrophilicity, PCL/P123 formulations were found to reduce HUVEC viability. Both PCL and PCL/P123 materials reduced primary aortic smooth muscle cells (PASM) viability after 48 h. In PCL formulations containing CIL, drug release caused a decrease in PASM viability. P123 blending with PCL was found to be as a useful pre-fabrication technique for modulating surface hydrophobicity of electrospun materials and the release profile of incorporated active substance. The cytotoxicity of P123 was evaluated to improve the design of drug-loaded vascular grafts for cardiovascular applications.

Asunto(s)

Sistema Cardiovascular/efectos de los fármacos , Cilostazol/química , Liberación de Fármacos/efectos de los fármacos , Poloxaleno/química , Poliésteres/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Músculo Liso Vascular/efectos de los fármacos , Tamaño de la Partícula , Poloxaleno/farmacología , Propiedades de Superficie

RESUMEN

In tissue engineering, it is common to mix drugs that can control proliferation and differentiation of cells into polymeric solutions as part of composite to get bioactive scaffolds. However, direct incorporation of drugs might potentially result in undesired burst release. To overcome this problem, here we developed electrospun multilayer drug loaded poly-l-lactic acid/pluronic P123 (PLLA-P123) composite scaffolds. The drug was loaded into the middle layer. The surface, the mechanical and physiochemical properties of the scaffolds were evaluated. The drug release profiles were monitored. Finally, the osteogenic proliferation and differentiation potential were determined. The scaffolds fabricated here have appropriate surface properties, but with different mechanical strength and osteogenic proliferation and differentiation. Multi-layer scaffolds where the drug was in the middle layer and PLLA-plasma and PLLA-P123 with cover layer showed the best osteogenic proliferation and differentiation than the other groups of scaffolds. The drug release profiles of the scaffolds were completely different: single layer scaffolds showed burst release within the first day, while multilayer scaffolds showed controlled release. Therefore, the multilayer drug loaded scaffolds prepared have dual benefits can provide both better osteogenesis and controlled release of drugs and bioactive molecules at the implant site.

Asunto(s)

Dexametasona/administración & dosificación , Sistemas de Liberación de Medicamentos , Nanofibras , Ingeniería de Tejidos/métodos , Adulto , Huesos/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Química Farmacéutica/métodos , Dexametasona/farmacología , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Persona de Mediana Edad , Osteogénesis/efectos de los fármacos , Poloxaleno/química , Poliésteres/química , Adulto Joven

RESUMEN

The present study was aimed to examine the interaction of two bile salts viz. sodium cholate (NaC) and sodium deoxycholate (NaDC) with three ethylene polyoxide-polypropylene polyoxide (PEO-PPO-PEO) triblock copolymers with similar PPO but varying PEO micelles with a focus on the effect of pH on mixed micelles. Mixed micelles of moderately hydrophobic Pluronic® P123 were examined in the presence of two bile salts and compared with those from very hydrophobic L121 and very hydrophilic F127. Both the bile salts increase the cloud point (CP) of copolymer solution and decreased apparent micelle hydrodynamic diameter (Dh). SANS study revealed that P123 forms small spherical micelles showing a decrease in size on progressive addition of bile salts. The negatively charged mixed micelles contained fewer P123 molecules but progressively rich in bile salt. NaDC being more hydrophobic displays more pronounced effect than NaC. Interestingly, NaC shows micellar growth in acidic media which has been attributed to the formation of bile acids by protonation of carboxylate ion and subsequent solubilization. In contrast, NaDC showed phase separation at higher concentration. Nuclear Overhauser effect spectroscopy (NOESY) experiments provided information on interaction and location of bile salts in micelles. Results are discussed in terms of hydrophobicity of bile salts and Pluronics® and the site of bile salt in polymer micelles. Proposed molecular interactions are useful to understand more about bile salts which play important role in physiological processes.

Asunto(s)

Ácidos y Sales Biliares/química , Micelas , Polímeros/química

RESUMEN

The aim of the current study was to formulate terconazole (TCZ) loaded polymeric mixed micelles (PMMs) incorporating Cremophor EL as a stabilizer and a penetration enhancer. A 23 full factorial design was performed using Design-Expert® software for the optimization of the PMMs which were formulated using Pluronic P123 and Pluronic F127 together with Cremophor EL. To confirm the role of Cremophor EL, PMMs formulation lacking Cremophor EL was prepared for the purpose of comparison. Results showed that the optimal PMMs formulation (F7, where the ratio of total Pluronics to drug was 40:1, the weight ratio of Pluronic P123 to Pluronic F127 was 4:1, and the percentage of Cremophor EL in aqueous phase was 5%) had a high micellar incorporation efficiency (92.98 ± 0.40%) and a very small micellar size (33.23 ± 8.00 nm). Transmission electron microscopy revealed that PMMs possess spherical shape and good dispersibility. The optimal PMMs exhibited superior physical stability when compared with the PMMs formulation of the same composition but lacking Cremophor EL. Ex vivo studies demonstrated that the optimal PMMs formula markedly improved the dermal TCZ delivery compared to PMMs lacking Cremophor EL and TCZ suspension. In addition, it was found that the optimal PMMs exhibited a greater extent of TCZ deposition in the rat dorsal skin relative to TCZ suspension. Moreover, histopathological studies revealed the safety of the optimal PMMs upon topical application to rats. Consequently, PMMs enriched with Cremophor EL, as a stable nano-system, could be promising for the skin delivery of TCZ.

Asunto(s)

Portadores de Fármacos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Glicerol/análogos & derivados , Micelas , Absorción Cutánea/efectos de los fármacos , Triazoles/administración & dosificación , Animales , Animales Recién Nacidos , Antifúngicos/administración & dosificación , Antifúngicos/química , Antifúngicos/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Composición de Medicamentos , Estabilidad de Medicamentos , Glicerol/administración & dosificación , Glicerol/química , Glicerol/metabolismo , Masculino , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Absorción Cutánea/fisiología , Tensoactivos/administración & dosificación , Tensoactivos/química , Tensoactivos/metabolismo , Triazoles/química , Triazoles/metabolismo

RESUMEN

Quercetin (QT) is a plant polyphenol with various pharmacological properties. However, the low water solubility limits its therapeutic efficacy. In the present study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed micelles were developed and characterized, and the effect of the formulation on improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed micelles were prepared by thin film hydration-direct dissolution and optimized by uniform design. The optimal formulation possessed high drug loading (12.6%) and entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A low critical micelle concentration indicated that the micelles were stable, and they showed a sustained release pattern, as determined in vitro in simulated gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed the Cmax and AUC0-24 were 1.8-fold and 1.6-fold higher than the QT suspension. The present results indicate that QT-loaded ST/P123 micelles are potential candidates to improve the solubility and oral bioavailability of QT.

Asunto(s)

Portadores de Fármacos/química , Micelas , Quercetina/administración & dosificación , Quercetina/química , Administración Oral , Animales , Líquidos Corporales/metabolismo , Liberación de Fármacos , Poloxaleno/química , Quercetina/farmacocinética , Ratas , Ratas Wistar , Solubilidad , Ácido Taurocólico/química , Distribución Tisular

RESUMEN

Poly-L-lactic acid (PLLA) nano fibrous scaffolds prepared by electrospinning technology have been used widely in tissue engineering applications. However, PLLA scaffolds are hydrophobic in nature, moreover the fibrous porous structure produced by electrospinning makes the scaffolds even more hydrophobic which generally limits cell attachment and proliferation. Polymer blending is one of the several efforts used so far to enhance hydrophilicity and recognized as an easy cost-effective approach for the manipulation physiochemical properties of polymeric biomaterials. Pluronic block copolymers containing hydrophilic poly(ethylene oxide) (PEO) blocks and hydrophobic poly(propylene oxide) (PPO) blocks are arranged in triblock structure: PEO-PPO-PEO. It is commonly used recently to blend hydrophobic polymers to enhance hydrophilicity for pharmaceutical and tissue engineering applications. In this study, novel pluronic P123 blend PLLA electrospun nanofibre scaffolds with improved hydrophilicity and biological properties were fabricated. The surface morphology and surface chemistry of the nanofibre scaffolds were characterized by scanning electron microscope (SEM) and FTIR analyses. Surface hydrophilicity and change in mechanical properties were studied. The ability of the scaffolds to support the attachment, and proliferation and differentiation of human adipose tissue derived MSCs, were evaluated generally. The fabricated scaffolds have completely improved, hydrophilicity, similar osteogenic differentiation potential with plasma-treated PLLA nanofibre scaffold, and hence P123 blend PLLA electrospun nanofibre scaffolds are a very good and cost effective choice as a scaffold for bone tissue engineering application.

Asunto(s)

Materiales Biocompatibles Revestidos/farmacología , Composición de Medicamentos/métodos , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Poloxaleno/química , Poliésteres/química , Andamios del Tejido/química , Tejido Adiposo/citología , Adulto , Fosfatasa Alcalina/metabolismo , Calcio/metabolismo , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Nanofibras/química , Nanofibras/ultraestructura , Propiedades de Superficie , Resistencia a la Tracción

RESUMEN

This review focuses on recent investigations that used Pluronic P123 (P123) as pharmaceutical ingredients in vesicle, micelle, mixed micelle, in situ gel, tablet and emulsion. The main results from these studies show that P123 can significantly increase the stability of incorporated hydrophobic drugs with enhanced in vitro cytotoxicity and cellular uptake of anticancer drugs. Moreover, modified forms of P123 with RGD, folate or other targeted marker have shown its therapeutic potentials in various types of tumors and cancers. Furthermore, modified forms of P123 alone and/or mixed with other copolymers have less toxic effects and more tumor-specific delivery of anticancer drugs. They are promising materials as a nanoplatform for the drug delivery. Finally, the future perspectives of the field are briefly discussed.

Asunto(s)

Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Poloxaleno/administración & dosificación , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Portadores de Fármacos/química , Estabilidad de Medicamentos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Oligopéptidos/administración & dosificación , Poloxaleno/efectos adversos , Poloxaleno/química