RESUMEN
Diabetic wounds (DWs) pose a significant health burden worldwide, with their management presenting numerous challenges. Biopolymeric formulations have recently gained attention as promising therapeutic approaches for diabetic wound healing. These formulations, composed of biocompatible and biodegradable polymers, offer unique properties such as controlled drug release, enhanced wound closure, and reduced scarring. In this review, we aim to provide a comprehensive overview of the current state of research and future prospects regarding the application of biopolymeric formulations for diabetic wound healing. The review begins by highlighting the underlying pathophysiology of DWs, including impaired angiogenesis, chronic inflammation, and compromised extracellular matrix (ECM) formation. It further explores the key characteristics of biopolymeric materials, such as their biocompatibility, biodegradability, and tunable physicochemical properties, which make them suitable for diabetic wound healing applications. The discussion further delves into the types of biopolymeric formulations utilized in the treatment of DWs. These include hydrogels, nanoparticles (NP), scaffolds, films, and dressings. Furthermore, the review addresses the challenges associated with biopolymeric formulations for diabetic wound healing. In conclusion, biopolymeric formulations present a promising avenue for diabetic wound healing. Their unique properties and versatility allow for tailored approaches to address the specific challenges associated with DWs. However, further research and developments are required to optimize their therapeutic efficacy, stability, manufacturing processes, and regulatory considerations. With continued advancements in biopolymeric formulations, the future holds great promise for improving the management and outcomes of DWs.
Asunto(s)
Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Humanos , Biopolímeros/química , Biopolímeros/administración & dosificación , Animales , Diabetes Mellitus/tratamiento farmacológico , Hidrogeles/química , Hidrogeles/administración & dosificación , Vendajes , Materiales Biocompatibles/química , Materiales Biocompatibles/administración & dosificación , Nanopartículas/químicaRESUMEN
There is a great demand for the development of novel wound dressings to overcome the time and costs of wound care performed by a vast number of clinicians, especially in the current overburdened healthcare systems. In this study, Cyanoflan, a biopolymer secreted by a marine unicellular cyanobacterium, was evaluated as a potential biomaterial for wound healing. Cyanoflan effects on cell viability, apoptosis, and migration were assessed in vitro, while the effect on tissue regeneration and biosafety was evaluated in healthy Wistar rats. The cell viability and apoptosis of fibroblasts and endothelial cells was not influenced by the treatment with different concentrations of Cyanoflan, as observed by flow cytometry. Moreover, the presence of Cyanoflan did not affect cell motility and migratory capacity, nor did it induce reactive oxygen species production, even revealing an antioxidant behavior regarding the endothelial cells. Furthermore, the skin wound healing in vivo assay demonstrated that Cyanoflan perfectly adapted to the wound bed without inducing systemic or local oxidative or inflammatory reaction. Altogether, these results suggest that Cyanoflan is a promising biopolymer for the development of innovative applications to overcome the many challenges that still exist in skin wound healing.
Asunto(s)
Materiales Biocompatibles/farmacología , Biopolímeros/farmacología , Cianobacterias/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/aislamiento & purificación , Biopolímeros/administración & dosificación , Biopolímeros/aislamiento & purificación , Línea Celular , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
Biopolymers and biocomposites have emerged as promising pathways to develop novel materials and substrates for biomedical applications [...].
Asunto(s)
Biopolímeros , Sistemas de Liberación de Medicamentos , Medicina Regenerativa/métodos , Animales , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Bioingeniería , Materiales Biomiméticos/química , Biopolímeros/administración & dosificación , Biopolímeros/química , Humanos , Andamios del Tejido/químicaRESUMEN
The main objectives of this study were to evaluate the chemical constitution and allergenic potential of red propolis extract (RPE). They were evaluated, using high performance liquid chromatography (HPLC) and the release of ß-hexosaminidase, respectively. A plethora of biologically active polyphenols and the absence of allergic responses were evinced. RPE inhibited the release of ß-hexosaminidase, suggesting that the extract does not stimulate allergic responses. Additionally, the physicochemical properties and antibacterial activity of hydrogel membranes loaded with RPE were analyzed. Bio-polymeric hydrogel membranes (M) were obtained using 5% carboxymethylcellulose (M1 and M2), 1.0% of citric acid (M3) and 10% RPE (for all). Their characterization was performed using thermal analysis, Fourier transform infrared (FTIR), total phenolic content, phenol release test and, antioxidant activity through 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and Ferric Reducing Antioxidant Power (FRAP). The latter appointed to the similar antioxidant capacity of the M1, M2 and M3. The degradation profiles showed higher thermostability to M3, followed by M2 and M1. The incorporation of RPE into the matrices and the crosslinking of M3 were evinced by FTIR. There were differences in the release of phenolic compounds, with a higher release related to M1 and lower in the strongly crosslinked M3. The degradation profiles showed higher thermostability to M3, followed by M2 and M1. The antibacterial activity of the membranes was determined using the disc diffusion assay, in comparison with controls, obtained in the same way, without RPE. The membranes elicited antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis, with superior performance over M3. The hydrogel membranes loaded with RPE promote a physical barrier against bacterial skin infections and may be applied in the wound healing process.
Asunto(s)
Própolis/química , Administración Tópica , Alérgenos/química , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Vendajes , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Biopolímeros/administración & dosificación , Biopolímeros/química , Biopolímeros/farmacología , Brasil , Línea Celular , Fenómenos Químicos , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Estabilidad de Medicamentos , Humanos , Hidrogeles , Técnicas In Vitro , Mastocitos/efectos de los fármacos , Mastocitos/enzimología , Mastocitos/inmunología , Membranas Artificiales , Fenoles/química , Própolis/administración & dosificación , Própolis/farmacología , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Termogravimetría , beta-N-Acetilhexosaminidasas/metabolismoRESUMEN
In the present study, we have demonstrated synthesis of agar aldehyde (Aald) from seaweed polysaccharide and its further successful application for preparation of Aald mediated solid silver nanocomposite (Aald-AgNPs). Aald-AgNPs were characterized for biophysical properties by FTIR, XRD, SEM, TEM, XPS, and UV-vis spectroscopy. Aald-AgNPs were further tested in vitro and in vivo for anticancer activity. The results of the in vitro study revealed that Aald-AgNPs exhibited activity against 3 cancer cell lines. Aald-AgNPs were found to act through causing dose dependent increase in cell size, inducing anueploidy, mitochondrial disintegration and increasing septa formation in cell cytoplasm. Results of in vivo anticancer activity against ME-180, Colon-26, and HL-60 xenograft mice tumor models showed 64 %, 27.3 % and 51 % reduction in tumor volume, respectively with 83-100 % survival rate. Aald-AgNPs exhibited excellent antibacterial activity. It was interesting to note that Aald-AgNPs did not exhibit any significant detrimental effect on viability and metabolic activity of normal bone marrow derived mesenchymal stem cells. This study opens new areas of research for chemists and biologists to use seaweed-derived polymers to develop nanocomposites for cancer therapeutics.
Asunto(s)
Agar/administración & dosificación , Aldehídos/administración & dosificación , Antineoplásicos/administración & dosificación , Biopolímeros/administración & dosificación , Nanopartículas del Metal/administración & dosificación , Nanocompuestos/administración & dosificación , Algas Marinas , Plata/administración & dosificación , Animales , Antibacterianos/administración & dosificación , Línea Celular Tumoral , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , Neoplasias/tratamiento farmacológicoRESUMEN
We integrate superparamagnetic iron oxide nanoparticles with polyaspartamide (PA) biopolymer to form a biological construct that functions as a tracking, targeting and drug-delivery system for cancer diagnosis and therapy. Iron oxide nanoparticles with uniformly distributed average spherical diameters of around 10 nm and superparamagnetic characteristics play a key role in increasing the transverse 1/T 2 relaxation rate or darkening the T 2-weighted MR image for cancer diagnosis using MRI. In in vitro MRI testing on cancer cells, the MR images of samples with the bio-constructshow a much clearer contrast effect than those of controls. The PA biopolymer plays an essential role in enhancing the hydrophilicity and biocompatibility of the bio-construct. In addition, as a multifunctional polymer, PA is conjugated with biotin and doxorubicin (Dox) functional groups to enhance targeting and impairment of cancer cells. In in vivo testing on cancer tumors, injection with the bio-construct decreased the magnitude of cancer tumor volume growth by three times compared with that of uninjected controls. The physicochemical characteristics of the bio-construct and the roles of biotin and Dox functional groups are examined and discussed in detail.
Asunto(s)
Antineoplásicos/administración & dosificación , Biopolímeros/administración & dosificación , Biotina/química , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Medios de Contraste/administración & dosificación , Células 3T3 , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Biopolímeros/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/química , Doxorrubicina , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas Magnéticas de Óxido de Hierro , Imagen por Resonancia Magnética , Ratones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Preeclampsia is a hypertensive disorder of pregnancy that causes significant acute and long-term risk to the mother and the baby. The multifaceted maternal syndrome is driven by overproduction of circulating anti-angiogenic factors, widespread inflammation, and endothelial dysfunction. Nuclear factor-κB (NF-κB) is a transcription factor that plays a central role in the inflammatory response. Its activity is increased in the preeclamptic placenta, and it promotes the systemic endothelial dysfunction present in preeclampsia. There is an acute need for new therapeutics targeted to the causative pathways of preeclampsia. Our group has developed a drug delivery system based on the bioengineered protein ELP (elastin-like polypeptide) that is capable of stabilizing therapeutics in the maternal circulation and preventing their placental transfer. Here we used the ELP carrier system to deliver a peptide known to inhibit the NF-κB pathway. This polypeptide, containing a cell-penetrating peptide and an NF-κB inhibitory peptide derived from the p50 nuclear localization sequence (abbreviated SynB1-ELP-p50i), blocked NF-κB activation and prevented TNF-α (tumor necrosis factor alpha)-induced endothelin production in vitro. Fusion of the p50i peptide to the SynB1-ELP carrier slowed its plasma clearance and prevented its placental transfer in pregnant rats, resulting in increased deposition in the maternal kidney, liver, and placenta relative to the free peptide. When administered in a rat model of placental ischemia, SynB1-ELP-p50i partially ameliorated placental ischemia-induced hypertension and reduced placental TNF-α levels with no signs of toxicity. These data support the continued development of ELP-delivered NF-κB inhibitors as maternally sequestered anti-inflammatory agents for preeclampsia therapy.
Asunto(s)
Biopolímeros/administración & dosificación , Sistemas de Liberación de Medicamentos , FN-kappa B/antagonistas & inhibidores , Péptidos/uso terapéutico , Preeclampsia/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Femenino , Péptidos/administración & dosificación , Preeclampsia/sangre , Embarazo , Ratas , Factor de Necrosis Tumoral alfa/sangreRESUMEN
When consumed at sufficiently high levels, polyphenols may provide health benefits, which is linked to their antidiabetic, antiinflamatory, antimicrobial, antioxidant, antitumor, and hypolipidemic properties. Moreover, certain polyphenol combinations exhibit synergistic effects when delivered together - the combined polyphenols have a higher biological activity than the sum of the individual ones. However, the commercial application of polyphenols as nutraceuticals is currently limited because of their poor solubility characteristics; instability when exposed to light, heat, and alkaline conditions; and, low and inconsistent oral bioavailability. Colloidal delivery systems are being developed to overcome these challenges. In this article, we review the design, fabrication, and utilization of food-grade biopolymer-based delivery systems for the encapsulation of one or more polyphenols. In particular, we focus on the creation of delivery systems constructed from edible proteins and polysaccharides. The optimization of biopolymer-based delivery systems may lead to the development of innovative polyphenol-enriched functional foods that can improve human health and wellbeing.
Asunto(s)
Biopolímeros/administración & dosificación , Suplementos Dietéticos , Sistemas de Liberación de Medicamentos , Alimentos Funcionales , Polifenoles/administración & dosificación , Polifenoles/farmacocinética , Disponibilidad Biológica , Biopolímeros/química , Biopolímeros/farmacocinética , Sinergismo Farmacológico , Humanos , Polifenoles/químicaRESUMEN
HYPOTHESIS AND BACKGROUND: The clinical treatment of sudden sensorineural hearing loss currently relies on the administration of steroids, either systemically or via intratympanic injections. Intratympanic injections bypass the hemato-cochlear barrier, reducing its systemic side effects. The efficacy of the injections is limited through rapid drug clearance via the Eustachian tube, and through nonoptimal properties of slow-release drug carriers. A new slow-release drug delivery vehicle based on hexyl-substituted-poly-lactic-acid (HexPLA), with the highest possible safety profile and complete bio-degradability, has been evaluated for safety and efficacy in a standardized guinea pig model of intratympanic injection. METHODS: A total of 83 animals received through retrobullar injection either empty Nile-red-colored HexPLA vehicle, 5%-dexamethasone-HexPLA, 5%-dexamethasone suspension, or a sham operation. Long-term residence time of vehicle, biocompatibility, click- and pure-tone hearing thresholds, and dexamethasone levels in the perilymph were prospectively assessed. RESULTS: At 1 week after injection, HexPLA vehicle was morphologically present in the middle ear and perilymph levels in the 5%-dexamethasone-HexPLA were on average 2 to 3âµg/ml and one order of magnitude higher compared with those of the 5%-dexamethasone suspension group. No significant postoperative morphological or functional changes were observed up to 3 months postdelivery. CONCLUSIONS: HexPLA is safe, fully biocompatible, and efficient for sustained high-dose, intratympanic delivery of dexamethasone at least for 1 week and therefore of high interest for the treatment of sudden sensorineural hearing loss and other acute inner ear diseases. Due to the favorable chemical properties, a wide range of other drugs can be loaded into the vehicle further increasing its potential value for otological applications.
Asunto(s)
Biopolímeros/administración & dosificación , Dexametasona/administración & dosificación , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Súbita/tratamiento farmacológico , Inyección Intratimpánica , Poliésteres/administración & dosificación , Membrana Timpánica/efectos de los fármacos , Animales , Preparaciones de Acción Retardada/administración & dosificación , Femenino , Cobayas , Audición/efectos de los fármacos , Resultado del TratamientoRESUMEN
Background and objectives: Cancer is the second leading cause of death globally, an alarming but expected increase. In comparison to other types of cancer, malignant bone tumors are unusual and their treatment is a real challenge. This paper's main purpose is the study of the potential application of composite scaffolds based on biopolymers and calcium phosphates with the inclusion of magnetic nanoparticles in combination therapy for malignant bone tumors. Materials and Methods: The first step was to investigate if X-rays could modify the scaffolds' properties. In vitro degradation of the scaffolds exposed to X-rays was analyzed, as well as their interaction with phosphate buffer solutions and cells. The second step was to load an anti-tumoral drug (doxorubicin) and to study in vitro drug release and its interaction with cells. The chemical structure of the scaffolds and their morphology were studied. Results: Analyses showed that X-ray irradiation did not influence the scaffolds' features. Doxorubicin release was gradual and its interaction with cells showed cytotoxic effects on cells after 72 h of direct contact. Conclusions: The obtained scaffolds could be considered in further studies regarding combination therapy for malignant bone tumors.
Asunto(s)
Biopolímeros/uso terapéutico , Neoplasias Óseas/terapia , Fosfatos de Calcio/uso terapéutico , Quimioradioterapia/métodos , Andamios del Tejido , Biopolímeros/administración & dosificación , Fosfatos de Calcio/administración & dosificación , Quimioradioterapia/normas , Humanos , Nanopartículas de Magnetita/administración & dosificación , Nanopartículas de Magnetita/uso terapéuticoRESUMEN
Electrospun nanofibers are known as the advanced means for wound dressing. They have represented remarkable potency to encapsulate and deliver biomolecules promoting the wound healing process. Compared to synthetic polymers, naturally derived polymers (NDP) are more qualified candidates for fabrication of biomedical electrospun scaffolds. Not only nanofibers of NDP illustrate higher biocompatibility and biodegradability rates, but also they mimic the native extracellular matrix more closely, which leads to the wound closure acceleration by enhancing tissue regeneration. Aside, incorporation of bioactive molecules and therapeutic agents into the nanofibers can generate innovative bioactive wound dressings with significantly improved healing potentials. This paper starts with a brief discussion on the steps and factors influencing the wound healing process. Then, the recent applications of electrospun nanofibers as wound dressing with healing accelerating properties are reviewed. Further, the various healing agents and alternative strategies for modification and functionalization of bioactive naturally-derived electrospun nanofibers are discussed.
Asunto(s)
Vendajes , Biopolímeros/administración & dosificación , Nanofibras/administración & dosificación , Animales , Humanos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND/AIMS: The management of patients with cirrhosis requiring dental extractions is complicated due to an increased risk of post-operative bleeding. Topical hemostatic agents are usually required to control bleeding in these cases, as an adjunct to systemic measures of hemostasis. The aims of this randomized, prospective, single-blind clinical study are twofold. The primary aim is to compare the hemostatic efficacy of chitosan and surgicel in patients with cirrhosis after a tooth extraction, and the secondary aim is to assess the value of the current setting as a clinical model of post-operative bleeding following minor oral surgery. MATERIAL AND METHODS: Fifty patients with cirrhosis scheduled for a tooth extraction under local anesthesia were prospectively included in the study in a randomized fashion. Patients were blinded to the treatment group they were in. The cirrhosis classification, bleeding time, trauma score, and corrected bleeding time (during post-operative reviews) were recorded. Statistical evaluations were done. RESULTS: Study groups had an equal number of teeth extractions (40 teeth each). There were no statistically significant differences between the groups with respect to patient demographics, cirrhosis classification, trauma score, and bleeding time. No side effects were noted. CONCLUSION: Both Celox and Surgicel are effective for controlling bleeding and are safe after a tooth extraction in patients with cirrhosis.
Asunto(s)
Biopolímeros/administración & dosificación , Celulosa Oxidada/administración & dosificación , Hemostáticos/administración & dosificación , Cirrosis Hepática/complicaciones , Hemorragia Posoperatoria/prevención & control , Extracción Dental/efectos adversos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Estudios Prospectivos , Método Simple Ciego , Resultado del Tratamiento , Adulto JovenRESUMEN
Intracellular drug delivery systems are often limited by their poor serum stability and delivery efficiency. Cell-penetrating peptides (CPPs), particularly those derived from basic protein subunits, have been studied extensively in this regard and used for the delivery of a variety of cargoes in vitro. Although promising, traditional cationic CPPs have some drawbacks that hinder their therapeutic application such as rapid proteolytic degradation and undesired interactions with the biological milieu. To overcome these limitations, this article details the discovery of a new class of noncharged cell-penetrating oligoTEAs (CPOTs) that undergo extensive and rapid cellular entry across different cell lines with low cytotoxicity. CPOTs outperform a widely used CPP, R9 peptide. This new class of highly efficient noncharged macromolecular transporters are distinct from their cationic counterparts and show strong promise for the intracellular delivery of hydrophilic small-molecule therapeutics.
Asunto(s)
Biopolímeros/administración & dosificación , Péptidos de Penetración Celular/administración & dosificación , Sistemas de Liberación de Medicamentos , Biopolímeros/química , Péptidos de Penetración Celular/química , Citoplasma/metabolismo , Endocitosis , Colorantes Fluorescentes/química , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , ProteolisisRESUMEN
AIM: Ebselen (Eb) is an example of a repurposed drug with poor aqueous solubility which requires sophisticated delivery system such as nanoencapsulation in nanocapsules for topical application. MATERIALS & METHODS: Eb-nanocapsules were examined for morphology, activity against Candida spp., cytotoxicity and skin permeation. RESULTS: Eb-nanocapsules were active against skin-infecting Candida tropicalis, Candida albicans and Candida parapsilosis yeasts (minimal inhibitory concentration values were about 4-, 2- and 1.25-times lower vs free Eb, respectively) and able to suppress induced lipid oxidation in the oil/water emulsion. Moreover, demonstrated minimal toxicity in normal human dermal fibroblast cell line, whereas ex vivo skin permeation studies showed no transdermal passage and strong interactions with stratum corneum. CONCLUSION: Eb-nanocapsules represent a promising, safe and complementary alternative to the treatment of cutaneous candidiasis.
Asunto(s)
Antifúngicos/administración & dosificación , Azoles/administración & dosificación , Candidiasis/tratamiento farmacológico , Nanocápsulas/administración & dosificación , Compuestos de Organoselenio/administración & dosificación , Administración Tópica , Antifúngicos/química , Azoles/química , Biopolímeros/administración & dosificación , Biopolímeros/química , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidad , Candidiasis/microbiología , Reposicionamiento de Medicamentos , Emulsiones/química , Humanos , Isoindoles , Pruebas de Sensibilidad Microbiana , Nanocápsulas/química , Compuestos de Organoselenio/químicaRESUMEN
Fibroblast growth factor 21 (FGF21) is under investigation as a type 2 diabetes protein drug, but its efficacy is impeded by rapid in vivo clearance and by costly production methods. To improve the protein's therapeutic utility, we recombinantly expressed FGF21 as a fusion with an elastin-like polypeptide (ELP), a peptide polymer that exhibits reversible thermal phase behavior. Below a critical temperature, ELPs exist as miscible unimers, while above, they associate into a coacervate. The thermal responsiveness of ELPs is retained upon fusion to proteins, which has notable consequences for the production and in vivo delivery of FGF21. First, the ELP acts as a solubility enhancer during E. coli expression, yielding active fusion protein from the soluble cell lysate fraction and eliminating the protein refolding steps that are required for purification of FGF21 from inclusion bodies. Second, the ELP's phase transition behavior is exploited for facile chromatography-free purification of the ELP-FGF21 fusion. Third, the composition and molecular weight of the ELP are designed such that the ELP-FGF21 fusion undergoes a phase transition triggered solely by body heat, resulting in an immiscible viscous phase upon subcutaneous (s.c.) injection and thereby creating an injectable depot. Indeed, a single s.c. injection of ELP-FGF21 affords up to five days of sustained glycemic control in ob/ob mice. The ELP fusion partner massively streamlines production and purification of FGF21, while providing a controlled release method for delivery that reduces the frequency of injection, thereby enhancing the pharmacological properties of FGF21 as a protein drug to treat metabolic disease.
Asunto(s)
Biopolímeros/metabolismo , Diabetes Mellitus Experimental/metabolismo , Elastina/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Calor , Hipoglucemiantes/metabolismo , Células 3T3 , Animales , Biopolímeros/administración & dosificación , Biopolímeros/química , Temperatura Corporal/fisiología , Preparaciones de Acción Retardada , Diabetes Mellitus Experimental/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos/métodos , Elastina/administración & dosificación , Elastina/química , Factores de Crecimiento de Fibroblastos/administración & dosificación , Factores de Crecimiento de Fibroblastos/química , Células HEK293 , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Masculino , Ratones , Ratones Obesos , Distribución AleatoriaRESUMEN
Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN-NH2) and then with hyaluronic acid, a biocompatible biopolymer which can be recognized by CD44 receptors in tumor cells, to obtain a targeting drug delivery system. To this purpose, three hyaluronic acid samples differing for the molecular weight, namely HAS (8-15â¯kDa), HAM (30-50â¯kDa) and HAL (90-130â¯kDa), were used. The MSN-HAS, MSN-HAM, and MSN-HAL materials were characterized through zeta potential and dynamic light scattering measurements at pHâ¯=â¯7.4 and Tâ¯=â¯37⯰C to simulate physiological conditions. While zeta potential showed an increasing negative value with the increase of the HA chain length, an anomalous value of the hydrodynamic diameter was observed for MSN-HAL, which was smaller than that of MSN-HAS and MSN-HAM samples. The cellular uptake of MSN-HA samples on HeLa cells at 37⯰C was studied by optical and electron microscopy. HA chain length affected significantly the cellular uptake that occurred at a higher extent for MSN-NH2 and MSN-HAS than for MSN-HAM and MSN-HAL samples. Cellular uptake experiments carried out at 4⯰C showed that the internalization process was inhibited for MSN-HA samples but not for MSN-NH2. This suggests the occurrence of two different mechanisms of internalization. For MSN-NH2 the uptake is mainly driven by the attractive electrostatic interaction with membrane phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed in HeLa cells.
Asunto(s)
Biopolímeros/química , Ácido Hialurónico/química , Nanopartículas/química , Dióxido de Silicio/química , Biopolímeros/administración & dosificación , Biopolímeros/farmacocinética , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Células HeLa , Humanos , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Nanopartículas/administración & dosificación , Nanopartículas/ultraestructura , Tamaño de la Partícula , PorosidadRESUMEN
BACKGROUND: Progressive thinning and dilation of the LV due to ischemic heart failure (IHF) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been used to increase wall thickness to reduce chamber volume, decrease wall stress, and improve cardiac function. We sought to evaluate the efficacy of a biopolymer (Algisyl-LVR) to prevent left ventricular (LV) remodeling in a swine model of IHF. METHODS: IHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Eight weeks later, Algisyl-LVR was injected into the LV myocardial free wall in five of the 11 animals. Echocardiographic examinations were done every 2weeks for 16weeks. RESULTS: Within eight weeks of treatment, the ejection fraction increased from 30.5%±7.7% to 42.4%±3.5% (treated group) vs. 37.3%±3.8% to 34.3%±2.9% (control), p<0.01. Stroke volume increased from 18.5±9.3mL to 41.3±13.3mL (treated group) vs. 25.4±2.3mL to 31.4±5.3mL (control), p<0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69±0.06cm to 0.81±0.13cm (treated group) vs. 0.73±0.09cm to 0.68±0.11cm (control), p<0.05. Sphericity index remained almost unchanged after treatment, although differences were found at the end of the study between both groups (p<0.001). Average myofiber stress changed from 16.3±5.8kPa to 10.2±4.0kPa (treated group) vs. 15.2±4.8kPa to 17.9±5.6kPa (control), p<0.05. CONCLUSIONS: Algisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling caused by IHF in swine.
Asunto(s)
Biopolímeros/administración & dosificación , Implantes de Medicamentos/administración & dosificación , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/tratamiento farmacológico , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/tratamiento farmacológico , Animales , Masculino , Volumen Sistólico/efectos de los fármacos , Volumen Sistólico/fisiología , Porcinos , Resultado del TratamientoRESUMEN
Due to changing lifestyles of modern world, cardiac failures are increasing day by day. Drug delivery systems that can overcome the drawbacks of conventional drug administration are highly desired. Diltiazem hydrochloride (DTZ) is a common and effective drug used for cardiac failures. However, its efficient loading, high bio availability and sustained transdermal release from polymer matrix are of high demand. Herein, the main objective was to fabricate a transdermal drug delivery system (TDDS) capable of efficient DTZ loading with sustained release. Owing to the high hydrophilicity of DTZ, a hydrophilic matrix comprising of poly ethylene glycol coated vinyl trimethoxy silane-g-chitosan (PEG@VTMS-g-CS) was developed. DTZ encapsulated copolymer was dispersed in matrices like sodium alginate (ALG), carboxy methyl cellulose (CMC) and poly vinyl alcohol (PVA). Economic viability and cosmetic attractiveness of the films were evaluated and optimum results were obtained for PVA matrix. The in vitro skin penetration study of DTZ on rat skin further demonstrated the efficacy of PVA based film which yielded more than 40.0% cell viability on HaCaT and PBMC cell line with no histological changes on the skin which further confirmed the practical utility of the prepared film.
Asunto(s)
Alginatos/química , Carboximetilcelulosa de Sodio/química , Diltiazem/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Administración Cutánea , Alginatos/administración & dosificación , Animales , Biopolímeros/administración & dosificación , Biopolímeros/química , Carboximetilcelulosa de Sodio/administración & dosificación , Quitosano/química , Diltiazem/química , Sistemas de Liberación de Medicamentos , Ácido Glucurónico/administración & dosificación , Ácido Glucurónico/química , Ácidos Hexurónicos/administración & dosificación , Ácidos Hexurónicos/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Leucocitos Mononucleares/efectos de los fármacos , Alcohol Polivinílico/administración & dosificación , Alcohol Polivinílico/química , RatasRESUMEN
BACKGROUND: The 'tumor microenvironment' comprised of tumor cells, non-malignant stromal tissues, signaling molecules and the extracellular matrix. Tumor microenvironment has unique physical and physiological characteristics including vascular abnormalities, hypoxia, acidic pH, specific enzymes and growth factors upregulation and high reducing potential. It is these endogenous properties of the tumor environment that can be used to trigger the release of cancer therapeutics both locally and as a function of disease state. Biopolymers such as proteins, polypeptides and polysaccharides are actively being designed to be bioresponsive nanocarriers for drug delivery due to their relative biocompatibility, biodegradability and low immunogenicity. OBJECTIVE: This review focuses on the use of physicochemical attributes of the endogenous tumor microenvironment to provide the impetus for on-demand release of therapeutics from biopolymer-based nanocarriers that are sensitive to pH, enzymes, redox conditions and combinations thereof. CONCLUSION: The development of multifunctional nanocarriers based upon a rational approach for targeting and delivering therapeutics to tumors is an area of active research. Despite the huge amount of work done in this area, especially using pH as a means of eliciting drug release at tumor sites, there is a dearth of work whereby different stages during tumor development are targeted for treatment. Although nanocarriers that are able to react to multiple components of the tumor microenvironment are starting to become common-place, it seems that the ability to release various factors at specific times crucial to therapy has not been studied to a large extent as a means of regaining tissue homeostasis.
Asunto(s)
Antineoplásicos/administración & dosificación , Biopolímeros/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Animales , Antineoplásicos/metabolismo , Biopolímeros/metabolismo , Doxorrubicina/administración & dosificación , Doxorrubicina/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Humanos , Nanopartículas/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral/fisiologíaRESUMEN
Non-specific distribution of chemotherapeutic agents in the body where they affect both cancer as well as normal cells resulting in serious side effects is the major reason for the high mortality rate of cancer. Thus, there is a need for developing targeted delivery strategies specially employing nanoplatform-based cancer therapies that provide specific targeting to tumor cells. In this regard, biopolymeric nanoplatforms such as liposomes, protein- and polysaccharide- based nanoparticles have gained more attention due to their biocompatibility, biodegradability and less toxicity. In terms of targeting, monoclonal antibodies (mAbs), folic acid (FA) and transferrin (Tf) can be considered as the moieties to be attached to the nanoplatforms to deliver their payload to its site of action. This review article focuses on the recent progress in the field of targeted drug and gene delivery systems with emphasizes on liposomes, protein (specially human and bovine serum albumin)-based nanoparticles and polysaccharide (specially chitosan and dextran)-based nanoparticles as the biopolymeric nanoplatforms, which are decorated with mAbs, FA and Tf as the targeting ligands.