RESUMEN

Microbial keratitis (MK) is a vision-threatening disease and the fourth leading cause of blindness worldwide. In this work, we aim to develop moxifloxacin (MXN)-loaded chitosan-based cationic mucoadhesive polyelectrolyte nanocapsules (PENs) for the effective treatment of MK. PENs were formulated by polyelectrolyte complex coacervation method and characterized for their particle size, surface charge, morphology, mucoadhesive property, in-vitro and ex-vivo release, ocular tolerance, and antimicrobial efficacy studies. The pharmacodynamic study was conducted on rabbit eye model of induced keratitis and it is compared with marketed formulation (MF). Developed PENs showed the size range from 230.7 ± 0.64 to 249.0 ± 0.49 nm and positive surface charge, spherical shape along with appropriate physico-chemical parameters. Both in-vitro and ex-vivo examination concludes that PENs having more efficiency in sustained release of MXN compared to MF. Ocular irritation studies demonstrated that no corneal damage or ocular irritation. The in-vivo study proved that the anti-bacterial efficacy of PENs was improved when compared with MF. These results suggested that PENs are a feasible choice for MK therapy because of their ability to enhance ocular retention of loaded MXN through interaction with the corneal surface of the mucous membrane.

Asunto(s)

Desarrollo de Medicamentos/métodos , Queratitis/tratamiento farmacológico , Moxifloxacino/síntesis química , Nanocápsulas/química , Polielectrolitos/síntesis química , Animales , Antibacterianos/administración & dosificación , Antibacterianos/síntesis química , Antibacterianos/farmacocinética , Embrión de Pollo , Córnea/efectos de los fármacos , Córnea/metabolismo , Córnea/microbiología , Cabras , Queratitis/metabolismo , Queratitis/microbiología , Moxifloxacino/administración & dosificación , Moxifloxacino/farmacocinética , Nanocápsulas/administración & dosificación , Polielectrolitos/administración & dosificación , Polielectrolitos/farmacocinética , Conejos

RESUMEN

Polyanions are negatively charged macromolecules known for several decades as inhibitors of many viruses in vitro, notably AIDS virus. In the case of enveloped viruses, this activity was assigned to the formation of a polyelectrolyte complex between an anionic species, the polyanion, and the spike cationic proteins which are, for polymer chemists, comparable to cationic polyelectrolytes. Unfortunately, in vitro antiviral activity was not confirmed in vivo, possibly because polyanions were captured by cationic blood elements before reaching target cells. Accordingly, virologists abandoned the use of polyanions for antiviral therapy. In the case of coronaviruses like SARS-CoV-2 and its mutants the game may not be over because these viruses infect cells of airways and not of blood. This communication proposes strategies to use polysulfates to attack and inhibit viral particles before they reach target cells in the airways. For this, polysulfate solutions may be administered by spray, gargling and nebulization or used to capture virus-containing droplets and aerosols by bubbling when these vectors are in the atmosphere. The technical means exist. However, biocompatibility and biofunctionality tests are necessary in the case of airways. Such tests require manipulation of pathogens, something which is beyond the competences of a biomaterialist. For this, a specialist in virology is necessary. Attempts to find one failed so far despite all-around solicitations over the past ten months and despite the fact that attacking the virus with polysulfates may complement beneficially the defensive strategies based on masks, vaccines and hospitals.

Asunto(s)

Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Polielectrolitos/farmacología , SARS-CoV-2/efectos de los fármacos , Sulfatos/farmacología , Microbiología del Aire , Antivirales/administración & dosificación , Antivirales/química , COVID-19/prevención & control , Humanos , Nebulizadores y Vaporizadores , Vaporizadores Orales , Polielectrolitos/administración & dosificación , Polielectrolitos/química , SARS-CoV-2/genética , Sulfatos/administración & dosificación , Sulfatos/química

RESUMEN

In situ simultaneous formation of both covalent linkages and ion pair is challenging yet necessary to control the biological properties of a hydrogel. We report that the generation of covalent linkages (+N-C) facilitates the simultaneous formation of ion pairs between polyelectrolytes (PEs) in a hydrogel network. Co-injection of tertiary amine functional macromolecules and reactive poly(ethylene glycol) (PEG) containing negatively charged PE leads to the formation of hydrogel conetworks consisting of covalent junctions and ion pairs. Our design is based on the gradual appearance of +N-C junctions followed by formation of ion pairs. This strategy provides an easy access to hydrogel networks bearing a predetermined proportion of ion pair and covalent cross-linking junction. The proportion of ion pair could be varied by introducing a precalculated proportion of mono- and difunctional reactive PEG in the hydrogel system. The topology of the prepolymer and the hydrogel could be modulated (graft) during hydrogel formation. This approach is applicable to obtain covalent/ionic, covalent bond induced purely ionic, and purely covalent hydrogels of several macromolecular entities. The effect of ion pairing in the hydrogels is strongly reflected in the modulus, strain bearing, degradation, free volume, swelling, and drug release properties. The hydrogels exhibit microscopic recovery of modulus after application of high amplitude strain depending on the prepolymer concentration (chain entanglement) and nature of hydrogel network. The hydrogels are hemocompatible, and the covalent/ionic hydrogels show a slower release of methotrexate than that of the purely covalent hydrogel. This work provides an understanding for the in situ construction and manipulation of biological properties of hydrogels through the covalent bond induced formation of a strong ion pair.

Asunto(s)

Materiales Biocompatibles/química , Hidrogeles/química , Polielectrolitos/química , Materiales Biocompatibles/administración & dosificación , Hidrogeles/administración & dosificación , Iones/administración & dosificación , Iones/química , Ensayo de Materiales , Estructura Molecular , Tamaño de la Partícula , Polielectrolitos/administración & dosificación

RESUMEN

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window exhibits enhanced deep-tissue imaging capability. Likely, cancer therapy in the NIR-II window could provide deeper penetration depth and higher exposure to laser over NIR-I. However, the traditional application of excitation light is still in the NIR-I window. In view of the excellent imaging and therapeutic capabilities of NIR-II window, we have demonstrated a simple polyoxometalate (POM) clusters (molecular formula: (Na)n(PMo12O40) or (NH4+)n(PMo12O40)), which integrates NIR-II photoacoustic imaging and NIR-II photothermal therapy into an "all-in-one" theranostic nanoplatform, and could be used for PA imaging-guided photothermal therapy in the NIR-II window. In vivo experiments demonstrate that the POM clusters with good water solubility and biocompatibility were effective to kill tumor without recurrence and metastasis under 1064 nm laser illumination.

Asunto(s)

Aniones/química , Nanopartículas/química , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Terapia Fototérmica/métodos , Polielectrolitos/química , Animales , Aniones/administración & dosificación , Línea Celular Tumoral , Humanos , Rayos Infrarrojos , Ratones , Molibdeno/química , Nanopartículas/administración & dosificación , Neoplasias/diagnóstico , Neoplasias/patología , Polielectrolitos/administración & dosificación , Nanomedicina Teranóstica/métodos

RESUMEN

Gene and nucleic acid delivery constitute a huge biological challenge and several attempts have been made by research laboratories to address this issue. Cationic polymers and cationic lipids (positively charged carriers) can be utilized for the transport of these biomolecules. Polyplexes (PPs) are interpolyelectrolyte complexes which are spontaneously formed through the electrostatic condensation between nucleic acid and a cationic polymer. PPs are capable of high-density payload condensation leading to cell internalization and subsequent protection from enzymatic degradation. Most cationic polymers can cross extracellular barriers, but it is more challenging to overcome intracellular barriers (efficient disassembly and endosomal escape). In this review, the use of PPs for gene and nucleic acid delivery is discussed.

Asunto(s)

Técnicas de Transferencia de Gen , Ácidos Nucleicos/administración & dosificación , Polielectrolitos/administración & dosificación , Animales , Humanos

RESUMEN

Previously, we reported on the surfactant cetylpyridinium chloride (CPC) as a crosslinker of alginate for the formation of stable polyelectrolyte-surfactant-complex nanoparticles. Here, we evaluate this system for increased solubility of a poorly soluble drug. The aim was to use CPC for solubilisation of ibuprofen and to use the micellar associates formed for alginate complexation and nanoparticle formation. We acquired deeper insights into the entropy led interactions between alginate, CPC and ibuprofen. Stable nanoparticles were formed across limited surfactant-to-polyelectrolyte molar ratios, with ~150 nm hydrodynamic diameter, monodispersed distribution, and negative zeta potential (-40 mV), with 34% ibuprofen loading. Their structure was obtained using small-angle X-ray scattering, which indicated disordered micellar associates when ibuprofen was incorporated. This resulted in nanoparticles with a complex nanostructured composition, as shown by transmission electron microscopy. Drug release from ibuprofen-cetylpyridinium-alginate nanoparticles was not hindered by alginate, and was similar to the release kinetics from ibuprofen-CPC solubilisates. These innovative carriers developed as polyelectrolyte-surfactant complexes can be used for solubilisation of poorly soluble drugs, where the surfactant simultaneously increases the solubility of the drug at concentrations below its critical micellar concentration and crosslinks the polyelectrolyte to form nanoparticles.

Asunto(s)

Alginatos/metabolismo , Cetilpiridinio/metabolismo , Ibuprofeno/metabolismo , Nanopartículas/metabolismo , Polielectrolitos/metabolismo , Tensoactivos/metabolismo , Alginatos/administración & dosificación , Alginatos/química , Cetilpiridinio/administración & dosificación , Cetilpiridinio/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Ibuprofeno/administración & dosificación , Ibuprofeno/química , Nanopartículas/administración & dosificación , Nanopartículas/química , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Dispersión del Ángulo Pequeño , Solubilidad , Tensoactivos/administración & dosificación , Tensoactivos/química , Termodinámica

RESUMEN

The construction of intelligent self-assembly systems with cancer targeting photodynamic therapy abilities is highly required for increasing the precise therapeutic efficiency in clinical treatment. Herein, a cationic water soluble conjugated polymer (PFT-SH) functionalized with thiol groups was designed and synthesized via a palladium-catalyzed Suzuki coupling reaction. Firstly, PFT-SH can enter cells and form loose aggregations by hydrophobic and π-π stacking interactions. Secondly, a high level of H2O2 in cancer cells oxidizes sulfhydryl groups to disulfide bonds and then forms more and larger aggregations. Finally, PFT-SH showed remarkable ROS producing ability under white light irradiation with 78% quantum yields (ΦΔ). Due to this unique self-aggregation property, PFT-SH was successfully used to achieve in situ self-assembly specifically inside cancer cells for targeted imaging. Both the specific aggregation of PFT-SH in cancer cells and its ROS producing ability led to its use in the targeted killing of cancer cells through efficient photodynamic therapy.

Asunto(s)

Neoplasias/tratamiento farmacológico , Polielectrolitos/administración & dosificación , Compuestos de Sulfhidrilo/administración & dosificación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Luz , Microscopía Confocal , Neoplasias/metabolismo , Fotoquimioterapia , Polielectrolitos/química , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Sulfhidrilo/química

RESUMEN

The development of polyelectrolyte-surfactant complexes (PESCs) has attracted extensive research interest in different fields of applications. However, the liquid state of PESCs has limited their utility in applications where solid materials are required. In this study, novel antibacterial fibers were fabricated via electrospinning PESCs in the solid state without any additives. The PESCs were prepared in aqueous mixtures of pre-hydrolyzed polyacrylonitrile (HPAN), a polyelectrolyte, and cetyltrimethyl ammonium chloride (CTAC), an antibacterial cationic surfactant, by taking advantage of the self-aggregation behavior of the polyelectrolyte and surfactant, which increased the antibacterial agent loading ability and, thus, the antibacterial activity of polymers. By release-killing and contact-killing mechanisms, the as-spun PESC nanofibrous membranes exhibited strong antibacterial ability against both Gram-positive and Gram-negative bacteria, killing 5 log CFU of E. coli and S. aureus within a contact time as short as 30 min. Furthermore, PESCs were blended with polycaprolactone (PCL) to prepare composite nanofibrous membranes as a novel wound dressing, which showed excellent antibacterial activity and favorable cytocompatibility, with the mechanical strength high enough to satisfy the clinical application requirements. The PESC fibers with durable antibacterial activity presented in the current work would be promising for medical applications.

Asunto(s)

Antibacterianos , Vendajes , Nanofibras , Polielectrolitos , Tensoactivos , Células 3T3 , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Supervivencia Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Ratones , Nanofibras/administración & dosificación , Nanofibras/química , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Tensoactivos/administración & dosificación , Tensoactivos/química , Tecnología Farmacéutica

RESUMEN

In this study we evaluate macroporous scaffolds made of alginate-chitosan polyelectrolyte complexes (PEC) as tools to optimize the results of soft tissues cell therapy. Cell therapy using mesenchymal stem cells (MSC) has become attractive for tissue repair and regeneration in a number of acute and chronic injuries. Unfortunately their low retention and/or survival after injection limit their beneficial effects. A biomaterial-assisted implantation, providing cells a three-dimensional (3D) microenvironment is a promising strategy. To this purpose, we designed a family of PEC scaffolds, and studied if they could meet the requirement of such application. Xray tomography showed that all PEC scaffolds present an interconnected macroporosity, and both rheology and tensile measurements reveal optimized mechanical properties (higher storage moduli and Young moduli) compared to alginate reference scaffolds. In vitro assays demonstrated their ability to allow MSC retention (higher than 90%), long-term viability and FGF2 secretion. Then, we used a skeletal muscle implantation model to assess the biological response to scaffolds graft, and showed that they support in vivo vascular formation within the implant-derived tissue. The combination of alginate/chitosan PEC scaffolds architecture and angiogenic potential make them appear as interesting tools to optimize MSC therapy results in soft tissues.

Asunto(s)

Alginatos/administración & dosificación , Quitosano/administración & dosificación , Isquemia/terapia , Trasplante de Células Madre Mesenquimatosas , Polielectrolitos/administración & dosificación , Andamios del Tejido/química , Alginatos/química , Animales , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Quitosano/química , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Masculino , Ensayo de Materiales , Células Madre Mesenquimatosas , Polielectrolitos/química , Porosidad , Cultivo Primario de Células , Ratas , Ratas Endogámicas Lew , Ingeniería de Tejidos

RESUMEN

Chitosan (CS) is a biodegradable and biocompatible polysaccharide which displays immune-stimulatory effects and anti-bacterial properties to facilitate wound closure. Over the years, different CS-based dressings have been developed; however, most of them are not fully biodegradable due to the involvement of synthetic polymers during dressing fabrication. In addition, preparation of many of these dressings is laborious, and may impose damaging effects on fragile therapeutic molecules. The objective of this study is to address these problems by developing a tunable, biocompatible, and biodegradable CS-based dressing for wound treatment. The dressing is fabricated via electrostatic interactions between CS and carmellose (CM). Its swelling properties, erosion behavior, loading efficiency and drug release sustainability can be tuned by simply changing the CS/CM mass-to-mass ratio. Upon loaded with minocycline hydrochloride, the dressing effectively protects the wound in mice from infection and enhances wound closure. Regarding its high tunability and promising in vivo performance, our dressing warrants further development as a user-friendly dressing for use in wound care.

Asunto(s)

Antibacterianos/administración & dosificación , Vendajes , Carboximetilcelulosa de Sodio/administración & dosificación , Quitosano/administración & dosificación , Sistemas de Liberación de Medicamentos , Minociclina/administración & dosificación , Células 3T3 , Animales , Antibacterianos/química , Carboximetilcelulosa de Sodio/química , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Femenino , Ratones , Ratones Endogámicos ICR , Minociclina/química , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Electricidad Estática , Cicatrización de Heridas

RESUMEN

Wound healing, when compromised, may be guided by biological cues such as Arg-Gly-Asp (RGD), a peptide known to induce cell adhesion and migration, eventually combined with adapted nanocarriers. Three different formulations were prepared and investigated in vitro for topical application. All formulations were based on carboxylated and trimethylated chitosan (CMTMC) displaying RGD. The polyelectrolyte nanocomplexes were prepared by mixing two oppositely charged polymers of CMTMC and chondroitin sulfate at different polymer ratios and subsequently characterized by dynamic light scattering and scanning electron microscopy. Hydrogels and foams with a high concentration of RGD-functionalized chitosan (3%) and hyaluronic acid (1.5%) that formed gel-embedded nanocomplexes were developed. In vitro assays showed absence of toxicity, ability to promote proliferation over 7 days and promotion of migration of human dermal fibroblasts treated with any of our formulations. These formulations were shown to be suitable for easy topical application and have the potential to accelerate wound healing.

Asunto(s)

Quitosano/administración & dosificación , Quitosano/química , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Cicatrización de Heridas/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Línea Celular , Fibroblastos/efectos de los fármacos , Humanos , Hidrogeles/química , Concentración de Iones de Hidrógeno , Oligopéptidos/administración & dosificación , Oligopéptidos/química , Polímeros/química , Piel/efectos de los fármacos

RESUMEN

Incorporating a biomimetic coating and integrating osteoinductive biomolecules into basic bone substitutes are two common strategies to improve osteogenic capabilities in bone tissue engineering. Currently, the underlying mechanism of osteoporosis (OP)-related deficiency of osteogenesis remains unclear, and few treatments target at OP-related bone regeneration. Herein, we describe a self-assembling polyelectrolyte multilayered (PEM) film coating with local immobilisation of calcitriol (Cal) in biphasic calcium phosphate (BCP) scaffolds to promote osteoporotic bone regeneration by targeting the calcium sensing receptor (CaSR). Methods: The ovariectomy-induced functional changes in bone marrow mesenchymal stem cells (BMSCs), protective effects of Cal, and the potential mechanism were all verified. A PEM film composed of hyaluronic acid (HA) and chitosan (Chi) was prepared through layer-by-layer self-assembly. The morphology, growth behaviour, and drug retention capability of the composite scaffolds were characterised, and their biocompatibility and therapeutic efficacy for bone regeneration were systematically explored in vitro and in vivo.Results: The osteogenic differentiation, adhesion, and proliferation abilities of ovariectomised rat BMSCs (OVX-rBMSCs) decreased, in accordance with the deficiency of CaSR. Cal effectively activated osteogenesis in these OVX-rBMSCs by binding specifically to the active pocket of the CaSR structure, while the biomimetic PEM coating augmented OVX-rBMSCs proliferation and adhesion due to its porous surface structure. The PEM-coated scaffolds showed advantages in Cal loading and retention, especially at lower drug concentrations. HA/Chi PEM synergised with Cal to improve the proliferation, adhesion, and osteogenesis of OVX-rBMSCs and promote bone regeneration and BCP degradation in the critical-size calvarial bone defect model of OVX rats. Conclusion: A composite scaffold based on BCP, created by simply combining a biomimetic PEM coating and Cal immobilisation, could be clinically useful and has marked advantages as a targeted, off-the-shelf, cell-free treatment option for osteoporotic bone regeneration.

Asunto(s)

Regeneración Ósea/efectos de los fármacos , Calcitriol/administración & dosificación , Hormonas y Agentes Reguladores de Calcio/administración & dosificación , Portadores de Fármacos/administración & dosificación , Hidroxiapatitas/administración & dosificación , Osteoporosis/tratamiento farmacológico , Polielectrolitos/administración & dosificación , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas , Resultado del Tratamiento

RESUMEN

Citalopram HCl (CH) is one of the few drugs which can be used safely in childhood psychiatric disorders. This study was focused on the preparation of interpenetrating polyelectrolytes nano-complexes (IPNC) to transform the hydrophilic carbohydrate polymers into an insoluble form. The IPNCs were loaded with CH to sustain its effect. The IPNC2 (composed of chitosan:pectin in a 3:1 ratio) showed the most extended drug release pattern (P < 0.05) and followed a Higuchi-order kinetics model. It was characterized using SEM, X-rays diffractometry, and FTIR. In-vivo studies were performed using immature rats with induced depression, and were based on the investigation of behavioral, biochemical, and histopathological changes at different time intervals up to 24 h. Rats treated with IPNC2 showed a significant more rapid onset of action and more extended effect in the behavioral tests, in addition to a significantly higher serotonin brain level up to 24 h, compared to rats treated with the market product (P < 0.05). The histopathological examination showed a profound amelioration of the cerebral cortex features of the depressed rats after IPNC2 administration. This study proves the higher efficacy and more extended effect of the new polyelectrolytes nano-complexes compared to the market product.

Asunto(s)

Antidepresivos de Segunda Generación/administración & dosificación , Quitosano/administración & dosificación , Citalopram/administración & dosificación , Nanoestructuras/administración & dosificación , Pectinas/administración & dosificación , Polielectrolitos/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Administración Oral , Animales , Antidepresivos de Segunda Generación/química , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Quitosano/química , Citalopram/química , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Depresión/tratamiento farmacológico , Depresión/patología , Liberación de Fármacos , Masculino , Nanoestructuras/química , Pectinas/química , Polielectrolitos/química , Ratas , Inhibidores Selectivos de la Recaptación de Serotonina/química

RESUMEN

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

Asunto(s)

Antibacterianos , Ciprofloxacina , Polielectrolitos , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/orina , Ciprofloxacina/administración & dosificación , Ciprofloxacina/química , Ciprofloxacina/farmacocinética , Ciprofloxacina/orina , Estudios Cruzados , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Método Doble Ciego , Liberación de Fármacos , Femenino , Voluntarios Sanos , Humanos , Masculino , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Polielectrolitos/farmacocinética , Comprimidos , Adulto Joven

RESUMEN

In this study, chitosan-alginate polyelectrolyte microparticles containing the antibiotic, vancomycin chloride were prepared using the ionotropic gelation (coacervation) technique. In vitro release and drug transport mechanisms were studied concerning the chitosan only and alginate only microparticles as a control group. Further, the effect of porosity on the drug transport mechanism was also studied for chitosan-alginate mixed particles produced by lyophilizing in contrast to the air-dried non-porous particles. According to the in vitro release data, alginate only and chitosan only microparticles showed burst release and prolonged release respectively. Chitosan-alginate lyophilized microparticles showed the best-controlled release of vancomycin with the average release of 22µg per day for 14days. Also, when increasing alginate concentration there was no increase in the release rate of vancomycin. The release data of all the microparticles were treated with Ritger-Peppas, Higuchi, Peppas-Sahlin, zero-order, and first-order kinetic models. The best fit was observed with Peppas-Sahlin model, indicating the drug transport mechanism was controlled by both Fickian diffusion and case II relaxations. Also, Fickian diffusion dominates the drug transport mechanism of all air-dried samples during the study period. However, the Fickian contribution was gradually reducing with time. Porosity significantly effects the drug transport mechanism as case II relaxation dominates after day 10 of the lyophilized microparticles.

Asunto(s)

Alginatos/farmacocinética , Quitosano/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Microesferas , Polielectrolitos/farmacocinética , Vancomicina/farmacocinética , Alginatos/administración & dosificación , Transporte Biológico/fisiología , Quitosano/administración & dosificación , Preparaciones de Acción Retardada , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/farmacocinética , Liberación de Fármacos/fisiología , Ácido Glucurónico/administración & dosificación , Ácido Glucurónico/farmacocinética , Ácidos Hexurónicos/administración & dosificación , Ácidos Hexurónicos/farmacocinética , Polielectrolitos/administración & dosificación , Vancomicina/administración & dosificación

RESUMEN

BACKGROUND: Despite having excellent anticancer efficacy and ability to knockdown gene expression, the therapeutic feasibility of Dicer-substrate small interfering RNA (DsiRNA) is limited due to its poor cellular uptake, chemical instability and rapid degradation in biological environments. OBJECTIVE: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA delivery to colon for the treatment of colorectal cancer. METHOD: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA from gastric milieu. RESULTS: The mean particle size and zeta potential of the prepared WSC-DsiRNA complexes were varied from 145 ± 4 nm to 867 ± 81 nm and +38 ± 4 to -6.2 ± 2.7 mV respectively, when the concentrations of WSC (0.1%, 0.2% and 0.3% w/v) and pectin (0.1%, 0.2% and 0.25% w/v) were varied. The electron microscopic analysis revealed that morphology of WSC-DsiRNA complexes was varied from smooth spherical to irregular spherical. Cytotoxicity analysis demonstrated that viability of colorectal adenocarcinoma cell was decreased when the dose of WSC-DsiRNA was increased over the incubation from 24 to 48 h. A significantly low cumulative release of DsiRNA in simulated gastric (<15%) and intestinal fluids (<30%) and a marked increase in its release (>90%) in simulated colonic fluid (SCF) evidenced the feasibility and suitability of WSC-DsiRNA complexes for the colonic delivery. CONCLUSION: These findings clearly indicated promising potential of WSC-DsiRNA complexes as a carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.

Asunto(s)

Quitosano/administración & dosificación , Colon/metabolismo , Nanopartículas/administración & dosificación , Pectinas/administración & dosificación , Polielectrolitos/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Liberación de Fármacos , Jugo Gástrico/química , Mucosa Gástrica/metabolismo , Humanos , Secreciones Intestinales/química , Nanopartículas/química , Pectinas/química , Polielectrolitos/química , ARN Interferente Pequeño/química

RESUMEN

This work focuses on the relevance of antibacterial nanofibers based on a polyelectrolyte complex formed between positively charged chitosan (CHT) and an anionic hydroxypropyl betacyclodextrin (CD)-citric acid polymer (PCD) complexing triclosan (TCL). The study of PCD/TCL inclusion complex and its release in dynamic conditions, a cytocompatibility study, and finally the antibacterial activity assessment were studied. The fibers were obtained by electrospinning a solution containing chitosan mixed with PCD/TCL inclusion complex. CHT/TCL and CHT-CD/TCL were also prepared as control samples. The TCL loaded nanofibers were analyzed by Scanning Electron Microscopy (SEM), Fourier Transformed Infrared spectroscopy (FTIR) and X-Ray Diffraction (XRD). Nanofibers stability and swelling behavior in aqueous medium were pH and CHT:PCD weight ratio dependent. Such results confirmed that CHT and PCD interacted through ionic interactions, forming a polyelectrolyte complex. A high PCD content in addition to a thermal post treatment at 90°C were necessary to reach a nanofibers stability during 15days in soft acidic conditions, at pH=5.5. In dynamic conditions (USP IV system), a prolonged release of TCL with a reduced burst effect was observed on CHT-PCD polyelectrolyte complex based fibers compared to CHT-CD nanofibers. These results were confirmed by a microbiology study showing prolonged antibacterial activity of the nanofibers against Escherichia coli and Staphylococcus aureus. Such results could be explained by the fact that the stability of the polyelectrolyte CHT-PCD complex in the nanofibers matrix prevented the diffusion of the PCD/triclosan inclusion complex in the supernatant, on the contrary of the similar system including cyclodextrin in its monomeric form.

Asunto(s)

Antibacterianos/química , Nanofibras/química , Triclosán/química , Animales , Antibacterianos/administración & dosificación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Celulosa/administración & dosificación , Celulosa/química , Quitosano/administración & dosificación , Quitosano/química , Ciclodextrinas/administración & dosificación , Ciclodextrinas/química , Liberación de Fármacos , Estabilidad de Medicamentos , Escherichia coli/efectos de los fármacos , Ratones , Nanofibras/administración & dosificación , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Solubilidad , Staphylococcus aureus/efectos de los fármacos , Tecnología Farmacéutica , Triclosán/administración & dosificación

RESUMEN

Novel fibrous materials with antioxidant and antibacterial properties from poly(3-hydroxybutyrate) (PHB), quaternized chitosan (QCh), κ-carrageenan (Car) and caffeic acid (CA) were obtained. These materials were prepared by applying electrospinning or electrospinning in conjunction with dip-coating and polyelectrolyte complex (PEC) formation. It was found that the CA release depended on the fiber composition. X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) revealed that CA incorporated in the fibers was in the amorphous state, whereas CA included in the coating was in the crystalline state. In contrast to the neat PHB mats, the CA-containing mats and the PEC QCh/Car-coated mats were found to kill the Gram-positive bacteria S. aureus and the Gram-negative bacteria E. coli and were effective in suppressing the adhesion of pathogenic bacteria S. aureus. Enhancement of the antioxidant activity of the fibrous materials containing both CA and QCh/Car coating was observed.

Asunto(s)

Antibacterianos/química , Antioxidantes/química , Ácidos Cafeicos/química , Carragenina/química , Quitosano/química , Hidroxibutiratos/química , Poliésteres/química , Antibacterianos/administración & dosificación , Antioxidantes/administración & dosificación , Adhesión Bacteriana , Compuestos de Bifenilo/química , Ácidos Cafeicos/administración & dosificación , Carragenina/administración & dosificación , Quitosano/administración & dosificación , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Hidroxibutiratos/administración & dosificación , Picratos/química , Polielectrolitos/administración & dosificación , Polielectrolitos/química , Poliésteres/administración & dosificación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/fisiología

RESUMEN

INTRODUCCIÓN: En la actualidad el priming (cebado) del oxigenador y el circuito de CEC lo están haciendo com Solución fisiológica, Ringer lactato y bicarbonato. Un preparado para mantener osmolaridad y pH. En algunos pacientes se les agrega manitol también. Además de los glóbulos rojos en pacientes neonatos y pediátricos. EFICACIA: La solución polielectrolitica isotónica es de uso habitual en la práctica clínica tanto en la población pediátrica como en la adulta en centros de elevado volumen quirúrgico, pero la evidencia solo está basada en la experiencia del uso. Podría constituir una buena estrategia de protección miocárdica en cirugía cardiaca. Surge la necesidad de evidencia solida (ECAs) que avalen estos resultados. SEGURIDAD: No existen evidencias de una mayor tasa de efectos adversos con alguno de los productos analizados en este informe Costo: El impacto económico en el hospital no sería tan grande. CONCLUSIÓN: Son necesarios estudios adicionales de corte prospectivo para corroborar estos datos.

Asunto(s)

Humanos , Polielectrolitos/administración & dosificación , Soluciones Isotónicas , Evaluación de la Tecnología Biomédica , Análisis Costo-Beneficio/economía