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1.
ACS Omega ; 6(33): 21368-21383, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34471741

RESUMO

The current study introduces two novel, smart polymer three-dimensional (3D)-printable interpenetrating polymer network (IPN) hydrogel biomaterials with favorable chemical, mechanical, and morphological properties for potential applications in traumatic brain injury (TBI) such as potentially assisting in the restoration of neurological function through closure of the wound deficit and neural tissue regeneration. Additionally, removal of injury matter to allow for the appropriate scaffold grafting may assist in providing a TBI treatment. Furthermore, due to the 3D printability of the IPN biomaterials, complex structures can be designed and fabricated to mimic the native shape and structure of the injury sight, which can potentially assist with neural tissue regeneration after TBI. In this study, a peptide-only approach was employed, wherein collagen and elastin in a blend with gelatin methacryloyl were prepared and crosslinked using either Irgacure or Irgacure and Genipin to form either a semi or full IPN hydrogel 3D-printable neuromimicking platform system, respectively. The scaffolds displayed favorable thermal stability and were amorphous in nature with high full width at half-maximum values. Furthermore, no alteration to the peptide secondary structure was noted using Fourier transform infrared spectroscopy. The IPN biomaterials have a stiffness of around 600 Pa and are suitable for softer tissue engineering applications-that is, the brain. Scanning electron micrographs indicated that the IPN biomaterials had a morphological structure with a significant resemblance to the native rat cortex. Both biomaterial scaffolds were shown to support the growth of PC12 cells over a 72 h period. Furthermore, the increased nuclear eccentricity and nuclear area were shown to support the postulation that the IPN biomaterials maintain the cells in a healthy state encouraging cellular mitosis and proliferation. The Genipin component of the full IPN was further shown to exhibit antimicrobial properties and this suggests that Genipin can prevent the growth of pathogens associated with postsurgical brain infections. In addition to these findings, the study presents an anomaly, wherein the full IPN is found to be more brittle than the semi IPN, a finding that is in contradiction with the literature. This research, therefore, contributes to the collection of potential biomaterials for TBI applications coupled with 3D printing and can assist in the progression of neural treatments toward patient-specific scaffolds through the development of custom scaffolds.

2.
Expert Opin Ther Pat ; 31(9): 851-865, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33832392

RESUMO

INTRODUCTION: : Among all the anti-schistosomal drugs, praziquantel has been the most widely used. However, some major challenges have been faced using the drug in the treatment of schistosome infections. AREAS COVERED: : Several approaches used in the synthesis of praziquantel aimed at reducing the time and cost of production, the toxicity and experimental harsh conditions are discussed. Also, patented methods involved in the pharmaceutical reformulation of praziquantel in the treatment of diverse endoparasitic infestations are reported. Additionally, future perspectives in terms of nanomedicine approach in the formulation of praziquantel are highlighted. EXPERT OPINION: : Lipid-based nanosystems (LBNSs) formulations can be used to overcome the shortcomings associated with the use of praziquantel in the schistosomiasis treatment due to their amphipathic nature. This could be a promising vehicle for the delivery of praziquantel, which could in turn improve the bioavailability, as well as reduce the frequent dose of the drug and improve patient compliance. This may sustain the release of the drug and improve the rapid conversion of the drug into inactive metabolite due to rapid metabolism. Additionally, LBNSs approach could increase and improve the lipophilicity of the drug, which could make it easier to interact with the hydrophobic cores of the worm tegument.


Assuntos
Anti-Helmínticos/administração & dosagem , Praziquantel/administração & dosagem , Esquistossomose/tratamento farmacológico , Animais , Anti-Helmínticos/farmacocinética , Anti-Helmínticos/farmacologia , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Humanos , Lipídeos/química , Adesão à Medicação , Nanoestruturas , Patentes como Assunto , Praziquantel/farmacocinética , Praziquantel/farmacologia , Esquistossomose/parasitologia
3.
Sci Rep ; 11(1): 3104, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542336

RESUMO

Three-dimensional porous scaffolds are widely employed in tissue engineering and regenerative medicine for their ability to carry bioactives and cells; and for their platform properties to allow for bridging-the-gap within an injured tissue. This study describes the effect of various methoxypolyethylene glycol (mPEG) derivatives (mPEG (-OCH3 functionality), mPEG-aldehyde (mPEG-CHO) and mPEG-acetic acid (mPEG-COOH)) on the morphology and physical properties of chemically crosslinked, semi-interpenetrating polymer network (IPN), chitosan (CHT)/mPEG blend cryosponges. Physicochemical and molecular characterization revealed that the -CHO and -COOH functional groups in mPEG derivatives interacted with the -NH2 functionality of the chitosan chain. The distinguishing feature of the cryosponges was their unique morphological features such as fringe thread-, pebble-, curved quartz crystal-, crystal flower-; and canyon-like structures. The morphological data was well corroborated by the image processing data and physisorption curves corresponding to Type II isotherm with open hysteresis loops. Functionalization of mPEG had no evident influence on the macro-mechanical properties of the cryosponges but increased the matrix strength as determined by the rheomechanical analyses. The cryosponges were able to deliver bioactives (dexamethasone and curcumin) over 10 days, showed varied matrix degradation profiles, and supported neuronal cells on the matrix surface. In addition, in silico simulations confirmed the compatibility and molecular stability of the CHT/mPEG blend compositions. In conclusion, the study confirmed that significant morphological variations may be induced by minimal functionalization and crosslinking of biomaterials.

4.
Pharmaceutics ; 13(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525495

RESUMO

This investigation focused on the design of an injectable nano-enabled thermogel (nano-thermogel) system to attain controlled delivery of p11 anti-angiogenic peptide for proposed effective prevention of neovascularisation and to overcome the drawbacks of the existing treatment approaches for ocular disorders characterised by angiogenesis, which employ multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) antibodies. Synthesis of a polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) triblock co-polymer was undertaken, followed by characterisation employing Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) to ascertain the chemical stability and integrity of the co-polymer instituted for nano-thermogel formulation. The p11 anti-angiogenic peptide underwent encapsulation within poly(lactic-co-glycolic acid) (PLGA) nanoparticles via a double emulsion solvent evaporation method and was incorporated into the thermogel following characterisation by scanning electron microscopy (SEM), zeta size and zeta-potential analysis. The tube inversion approach and rheological analysis were employed to ascertain the thermo-sensitive sol-gel conversion of the nano-thermogel system. Chromatographic assessment of the in vitro release of the peptide was performed, with stability confirmation via Tris-Tricine PAGE (Polyacrylamide Gel Electrophoresis). In vitro biocompatibility of the nano-thermogel system was investigated employing a retinal cell line (ARP-19). A nanoparticle size range of 100-200 nm and peptide loading efficiency of 67% was achieved. Sol-gel conversion of the nano-thermogel was observed between 32-45 °C. Release of the peptide in vitro was sustained, with maintenance of stability, for 60 days. Biocompatibility assessment highlighted 97-99% cell viability with non-haemolytic ability, which supports the potential applicability of the nano-thermogel system for extended delivery of peptide for ocular disorder treatment.

5.
Drug Deliv Transl Res ; 11(5): 1903-1923, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33454927

RESUMO

The last 30 years has seen a proliferation of research on protein-resistant biomaterials targeted at designing bio-inert surfaces, which are prerequisite for optimal performance of implantable devices that contact biological fluids and tissues. These efforts have only been able to yield minimal results, and hence, the ideal anti-fouling biomaterial has remained elusive. Some studies have yielded biomaterials with a reduced fouling index among which high molecular weight polyethylene glycols have remained dominant. Interestingly, the field of implantable ocular devices has not experienced an outflow of research in this area, possibly due to the assumption that biomaterials tested in other body fluids can be translated for application in the ocular space. Unfortunately, progression in the molecular understanding of many ocular conditions has brought to the fore the need for treatment options that necessitates the use of anti-fouling biomaterials. From the earliest implanted horsehair and silk seton for glaucoma drainage to the recent mini telescopes for sight recovery, this review provides a concise incursion into the gradual evolution of biomaterials for the design of implantable ocular devices as well as approaches used to overcome the challenges with fouling. The implication of fouling for drug delivery, the design of immune-responsive biomaterials, as well as advanced surface immobilization approaches to support the overall performance of implantable ocular devices are also reviewed.


Assuntos
Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Polietilenoglicóis , Proteínas
6.
Drug Deliv Transl Res ; 11(1): 24-48, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32323161

RESUMO

Recent research has been successful in demonstrating the importance of the addition of platelets to the field of cell-mediated therapeutics, by making use of different platelet forms to design modalities able to positively impact a wide range of diseases. A key obstacle hindering the success of conventional therapeutic interventions is their inability to produce targeted treatment, resulting in a number of systemic side effects and a longer duration for the onset of action to occur. An additional challenge facing current popular therapeutic interventions is biocompatibility of the system, resulting in the decline of patient compliance to treatment. In an attempt to address these challenges, the past few decades have been witness to the discovery and innovation of precision therapy, in order to achieve targeted treatment for an array of conditions, thereby superseding alternative mechanisms of treatment. Platelet-mediated therapeutics, as well as employing platelets as drug delivery vehicles, are key components in advancing precision therapy within research and in clinical settings. This novel approach is designed with the objective that the platelets retain their original structure and functions within the body, thereby mitigating biocompatibility challenges. In this article, we review the current significant impact that the addition of platelet-inspired systems has made on the field of therapeutics; explore certain limitations of each system, together with ideas on how to overcome them; and discuss the clinical implications and future potential of platelet-inspired therapeutics. Graphical abstract.


Assuntos
Plaquetas , Humanos
7.
Nanomedicine (Lond) ; 15(30): 2955-2970, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33252322

RESUMO

Aim: In this study, curcumin was encapsulated in niosomes (Nio-Curc) to increase its effectiveness for the treatment of asthma. Materials & methods: The formulation underwent various physicochemical characterization experiments, an in vitro release study, molecular simulations and was evaluated for in vitro anti-inflammatory activity. Results: Results showed that Nio-Curc had a mean particle size of 284.93 ± 14.27 nm, zeta potential of -46.93 and encapsulation efficacy of 99.62%, which demonstrates optimized physicochemical characteristics. Curcumin release in vitro could be sustained for up to 24 h. Additionally, Nio-Curc effectively reduced mRNA transcript expression of pro-inflammatory markers; IL-6, IL-8, IL-1ß and TNF-α in immortalized human airway basal cell line (BCi-NS1.1). Conclusion: In this study, we have demonstrated that Nio-Curc mitigated the mRNA expression of pro-inflammatory markers in an in vitro study, which could be applied to treatment of asthma with further studies.


Assuntos
Asma , Curcumina , Asma/tratamento farmacológico , Curcumina/farmacologia , Humanos , Lipossomos , Tamanho da Partícula , RNA Mensageiro/genética
8.
Molecules ; 25(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003358

RESUMO

Synthesis of a novel theranostic molecule for targeted cancer intervention. A reaction between curcumin and lawsone was carried out to yield the novel curcumin naphthoquinone (CurNQ) molecule (2,2'-((((1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl) bis(2-methoxy-4,1-phenylene))bis(oxy))bis(naphthalene-1,4-dione). CurNQ's structure was elucidated and was fully characterized. CurNQ was demonstrated to have pH specific solubility, its saturation solubility increased from 11.15 µM at pH 7.4 to 20.7 µM at pH 6.8. This pH responsivity allows for cancer targeting (Warburg effect). Moreover, CurNQ displayed intrinsic fluorescence, thus enabling imaging and detection applications. In vitro cytotoxicity assays demonstrated the chemotherapeutic properties of CurNQ as CurNQ reduced cell viability to below 50% in OVCAR-5 and SKOV3 ovarian cancer cell lines. CurNQ is a novel theranostic molecule for potential targeted cancer detection and treatment.


Assuntos
Curcumina/uso terapêutico , Naftoquinonas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Camundongos , Células NIH 3T3 , Naftoquinonas/química , Naftoquinonas/farmacologia , Neoplasias Ovarianas/patologia , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Fluorescência
9.
Pharmaceutics ; 12(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007830

RESUMO

Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have yielded consummate results of clinical efficacy. N-acetylcysteine has shown neuroprotective potential. To this end, we developed a N-acetylcysteine (NAC)-loaded poly(lactic-co-glycolic acid) (PLGA) electrospun system for potential neural tissue application for TBI. Scanning electron microscopy showed nanofiber diameters ranging 72-542 nm and 124-592 nm for NAC-free and NAC-loaded PLGA nanofibers, respectively. NAC loading was obtained at 28%, and drug entrapment efficacy was obtained at 84%. A biphasic NAC release pattern that featured an initial burst release (13.9%) stage and a later sustained release stage was noted, thus enabling the prolonged replenishing of NAC and drastically improving cell viability and proliferation. This was evidenced by a significantly higher cell viability and proliferation on NAC-loaded nanofibers for rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines in comparison to PLGA-only nanofibers. The increased cell viability and cell proliferation on NAC-loaded nanofiber substantiates for the repositioning of NAC as a pharmacological agent in neural tissue regeneration applications.

10.
Polymers (Basel) ; 12(9)2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32825546

RESUMO

Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.

11.
Theranostics ; 10(19): 8691-8704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754272

RESUMO

Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H2O2-responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. Methods: Gold nanoparticles were modified with H2O2-responsive amphiphilic block copolymer PEG45-b-PABE330 by ligand exchange. The TPZ and GOx loaded GVs (TG-GVs) were prepared through the self-assembly of PEG45-b-PABE330 -grafted nanoparticles together with TPZ and GOx by solvent displacement method. Results: In response to H2O2 in tumor, the TG-GVs dissociate to release the payloads that are, otherwise, retained inside the vesicles for days without noticeable leakage. The released GOx enzymes catalyze the oxidation of glucose by oxygen in the tumor tissue to enhance the degree of hypoxia that subsequently triggers the reduction of hypoxia-activated pro-drug TPZ into highly toxic free radicals. The H2O2 generated in the GOx-catalyzed reaction also accelerate the dissociation of vesicles and hence the release rate of the cargoes in tumors. The drug-loaded GVs exhibit superior tumor inhibition efficacy in 4T1 tumor-bearing mice owing to the synergistic effect of chemo/starvation therapy, in addition to their use as contrast agents for computed tomography imaging of tumors. Conclusion: This nanoplatform may find application in managing tumors deeply trapped in viscera or other important tissues that are not compatible with external stimulus (e.g. light).


Assuntos
Neoplasias da Mama/tratamento farmacológico , Glucose Oxidase/administração & dosagem , Ouro/química , Peróxido de Hidrogênio/metabolismo , Tirapazamina/administração & dosagem , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Glucose Oxidase/química , Glucose Oxidase/farmacologia , Humanos , Nanopartículas Metálicas , Camundongos , Tirapazamina/química , Tirapazamina/farmacologia , Tomografia Computadorizada por Raios X , Hipóxia Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Molecules ; 25(14)2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32664504

RESUMO

Tankyrase enzymes (TNKS), a core part of the canonical Wnt pathway, are a promising target in the search for potential anti-cancer agents. Although several hundreds of the TNKS inhibitors are currently known, identification of their novel chemotypes attracts considerable interest. In this study, the molecular docking and machine learning-based virtual screening techniques combined with the physico-chemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) profile prediction and molecular dynamics simulations were applied to a subset of the ZINC database containing about 1.7 M commercially available compounds. Out of seven candidate compounds biologically evaluated in vitro for their inhibition of the TNKS2 enzyme using immunochemical assay, two compounds have shown a decent level of inhibitory activity with the IC50 values of less than 10 nM and 10 µM. Relatively simple scores based on molecular docking or MM-PBSA (molecular mechanics, Poisson-Boltzmann, surface area) methods proved unsuitable for predicting the effect of structural modification or for accurate ranking of the compounds based on their binding energies. On the other hand, the molecular dynamics simulations and Free Energy Perturbation (FEP) calculations allowed us to further decipher the structure-activity relationships and retrospectively analyze the docking-based virtual screening performance. This approach can be applied at the subsequent lead optimization stages.


Assuntos
Inibidores Enzimáticos , Tanquirases , Sítios de Ligação , Descoberta de Drogas , Inibidores Enzimáticos/química , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Tanquirases/antagonistas & inibidores , Tanquirases/química
13.
J Biomed Mater Res A ; 108(12): 2324-2350, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32363804

RESUMO

The loss of tissues and organs through injury and disease has stimulated the development of therapeutics that have the potential to regenerate and replace the affected tissue. Such therapeutics have the benefit of reducing the reliance and demand for life-saving organ transplants. Of the several regenerative strategies, 3D printing has emerged as the forerunner in regenerative attempts due to the fact that biologically and anatomically correct 3D structures can be fabricated according to the specified need. Despite the progress in this field, improvement is still limited by the difficulty in fabricating scaffolds that adequately mimic the native cellular microenvironment. In response, despite the complexities of the native extracellular matrix (ECM), the inclusion of ECM components into bioinks has emerged as a cutting-edge research area in terms of providing possible ECM-mimicking abilities of the 3D printed constructs. Furthermore, the development of ECM-mimicking scaffolds can potentially assist in improving personalized patient treatments. This review provides a critical analysis of selected naturally occurring ECM components as well as synthetic self-assembling peptides in their ability to provide the required ECM microenvironment for tissue regeneration. The success and possible short comings of each material, as well as the specific characteristics of each bioink, are evaluated.


Assuntos
Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Matriz Extracelular/química , Peptídeos/química , Alicerces Teciduais/química , Animais , Bioimpressão/métodos , Humanos , Impressão Tridimensional , Engenharia Tecidual/métodos
14.
Curr Pharm Des ; 26(19): 2207-2221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32238132

RESUMO

Carbon nanodots are zero-dimensional spherical allotropes of carbon and are less than 10nm in size (ranging from 2-8nm). Based on their biocompatibility, remarkable water solubility, eco- friendliness, conductivity, desirable optical properties and low toxicity, carbon dots have revolutionized the biomedical field. In addition, they have intrinsic photo-luminesce to facilitate bio-imaging, bio-sensing and theranostics. Carbon dots are also ideal for targeted drug delivery. Through functionalization of their surfaces for attachment of receptor-specific ligands, they ultimately result in improved drug efficacy and a decrease in side-effects. This feature may be ideal for effective chemo-, gene- and antibiotic-therapy. Carbon dots also comply with green chemistry principles with regard to their safe, rapid and eco-friendly synthesis. Carbon dots thus, have significantly enhanced drug delivery and exhibit much promise for future biomedical applications. The purpose of this review is to elucidate the various applications of carbon dots in biomedical fields. In doing so, this review highlights the synthesis, surface functionalization and applicability of biodegradable polymers for the synthesis of carbon dots. It further highlights a myriad of biodegradable, biocompatible and cost-effective polymers that can be utilized for the fabrication of carbon dots. The limitations of these polymers are illustrated as well. Additionally, this review discusses the application of carbon dots in theranostics, chemo-sensing and targeted drug delivery systems. This review also serves to discuss the various properties of carbon dots which allow chemotherapy and gene therapy to be safer and more target-specific, resulting in the reduction of side effects experienced by patients and also the overall increase in patient compliance and quality of life.


Assuntos
Carbono , Pontos Quânticos , Diagnóstico por Imagem , Sistemas de Liberação de Medicamentos , Terapia Genética , Humanos , Qualidade de Vida
15.
Artigo em Inglês | MEDLINE | ID: mdl-32266248

RESUMO

There are many challenges involved in ocular drug delivery. These are a result of the many tissue barriers and defense mechanisms that are present with the eye; such as the cornea, conjunctiva, the blinking reflex, and nasolacrimal drainage system. This leads to many of the conventional ophthalmic preparations, such as eye drops, having low bioavailability profiles, rapid removal from the administration site, and thus ineffective delivery of drugs. Hydrogels have been investigated as a delivery system which is able to overcome some of these challenges. These have been formulated as standalone systems or with the incorporation of other technologies such as nanoparticles. Hydrogels are able to be formulated in such a way that they are able to change from a liquid to gel as a response to a stimulus; known as "smart" or stimuli-responsive biotechnology platforms. Various different stimuli-responsive hydrogel systems are discussed in this article. Hydrogel drug delivery systems are able to be formulated from both synthetic and natural polymers, known as biopolymers. This review focuses on the formulations which incorporate biopolymers. These polymers have a number of benefits such as the fact that they are biodegradable, biocompatible, and non-cytotoxic. The biocompatibility of the polymers is essential for ocular drug delivery systems because the eye is an extremely sensitive organ which is known as an immune privileged site.

16.
Int J Mol Sci ; 21(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218381

RESUMO

Currently, there is a lack of ultrasensitive diagnostic tool to detect some diseases such as ischemic stroke, thereby impacting effective and efficient intervention for such diseases at an embryonic stage. In addition to the lack of proper detection of the neurological diseases, there is also a challenge in the treatment of these diseases. Carbon nanotubes have a potential to be employed in solving the theragnostic challenges in those diseases. In this study, carbon nanotubes were successfully synthesized for potential application in the detection and treatment of the neurological diseases such as ischemic stroke. Vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) were purified with HCl, carboxylated with H2SO4:HNO3 (3:1) and acylated with SOCl2 for use in potential targeting studies and for the design of a carbon-based electrode for possible application in the diagnosis of neurological diseases, including ischemic stroke. MWCNTs were washed, extracted from the filter membranes and dried in a vacuum oven at 60 °C for 24 h prior to functionalization and PEGylation. CNTs were characterized by SEM, TEM, OCA, DLS, CV and EIS. The HCl-treated CNT obtained showed an internal diameter, outer diameter and thickness of 8 nm, 34 nm and 75 µm, while these parameters for the H2SO4-HNO3-treated CNT were 8 nm, 23 nm and 41µm, respectively. PEGylated CNT demonstrated zeta potential, polydispersive index and particle size distribution of 6 mV, 0.41 and 98 nm, respectively. VA-MWCNTs from quartz tube were successfully purified, carboxylated, acylated and PEGylated for potential functionalization for use in targeting studies. For designing the carbon-based electrode, VA-MWCNTs on silicon wafer were successfully incorporated into epoxy resin for diagnostic applications. Functionalized MWCNTs were nontoxic towards PC-12 neuronal cells. In conclusion, vertically super-aligned MWCNTs have been successfully synthesized and functionalized for possible theragnostic biomedical applications in neurological disorders such as ischemic stroke.


Assuntos
Nanotubos de Carbono , Eletrodos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Nanotubos de Carbono/ultraestrutura , Oxirredução , Tamanho da Partícula
17.
Artigo em Inglês | MEDLINE | ID: mdl-32117928

RESUMO

Polymeric biomaterials have found widespread applications in nanomedicine, and poly(lactide-co-glycolide), (PLGA) in particular has been successfully implemented in numerous drug delivery formulations due to its synthetic malleability and biocompatibility. However, the need for preconception in these formulations is increasing, and this can be achieved by selection and elimination of design variables in order for these systems to be tailored for their specific applications. The starting materials and preparation methods have been shown to influence various parameters of PLGA-based nanocarriers and their implementation in drug delivery systems, while the implementation of computational simulations as a component of formulation studies can provide valuable information on their characteristics. This review provides a critical summary of the synthesis and applications of PLGA-based systems in bio-medicine and outlines experimental and computational design considerations of these systems.

18.
Carbohydr Polym ; 235: 115932, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122476

RESUMO

Biomaterials that function as tissue surrogates ought to form three dimensional structures which are conducive to cell proliferation and regeneration. Since the extracellular matrix (ECM) is composed of proteoglycans (long chain polysaccharides) and proteins, the combination of proteins and polysaccharides presents a logical strategy to mimic the ECM and guide cell growth and proliferation. Polysaccharides are distinctive scaffold materials for regeneration due to their biocompatibility, hydrophilicity, biodegradability and functional groups which may be modified to improve mechanical properties and cell signalling. However, modification of polysaccharides is often time consuming, and requires extensive chemical reactions. Therefore, to improve physiological signalling, tissue response and mechanical strength, polysaccharides are combined with proteins. This review will focus on naturally occurring proteins and polysaccharide combinations as well as draw attention to their specific use within the tissue engineering field.


Assuntos
Materiais Biocompatíveis/química , Polissacarídeos/química , Proteínas/química , Engenharia Tecidual , Animais , Configuração de Carboidratos , Proliferação de Células , Matriz Extracelular/química , Humanos , Tamanho da Partícula , Propriedades de Superfície
19.
Cancers (Basel) ; 12(2)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102429

RESUMO

Routes of drug administration and their corresponding physiochemical characteristics play major roles in drug therapeutic efficiency and biological effects. Each route of delivery has favourable aspects and limitations. The oral route of delivery is the most convenient, widely accepted and safe route. However, the oral route of chemotherapeutics to date have displayed high gastric degradation, low aqueous solubility, poor formulation stability and minimum intestinal absorption. Thus, mainstream anti-cancer drugs in current formulations are not suitable as oral chemotherapeutic formulations. The use of biopolymers such as chitosan, gelatin, hyaluronic acid and polyglutamic acid, for the synthesis of oral delivery platforms, have potential to help overcome problems associated with oral delivery of chemotherapeutics. Biopolymers have favourable stimuli-responsive properties, and thus can be used to improve oral bioavailability of anti-cancer drugs. These biopolymeric formulations can protect gastric-sensitive drugs from pH degradation, target specific binding sites for targeted absorption and consequently control drug release. In this review, the use of various biopolymers as oral drug delivery systems for chemotherapeutics will be discussed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32083071

RESUMO

Schistosomiasis is one of the major parasitic diseases and second most prevalent among the group of neglected diseases. The prevalence of schistosomiasis may be due to environmental and socio-economic factors, as well as the unavailability of vaccines for schistosomiasis. To date, current treatment; mainly the drug praziquantel (PZQ), has not been effective in treating the early forms of schistosome species. The development of drug resistance has been documented in several regions globally, due to the overuse of PZQ, rate of parasitic mutation, poor treatment compliance, co-infection with different strains of schistosomes and the overall parasite load. Hence, exploring the schistosome tegument may be a potential focus for the design and development of targeted anti-schistosomal therapy, with higher bioavailability as molecular targets using nanotechnology. This review aims to provide a concise incursion on the use of various advance approaches to achieve targeted anti-schistosomal therapy, mainly through the use of nano-enabled drug delivery systems. It also assimilates the molecular structure and function of the schistosome tegument and highlights the potential molecular targets found on the tegument, for effective specific interaction with receptors for more efficacious anti-schistosomal therapy.

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