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To date, nanomaterials have been widely used for the treatment and diagnosis of rheumatoid arthritis. Amongst various nanomaterials, polymer-based nanomaterials are becoming increasingly popular in nanomedicine due to their functionalised fabrication and easy synthesis, making them biocompatible, cost-effective, biodegradable, and efficient nanocarriers for the delivery of drugs to a specific target cell. They act as photothermal reagents with high absorption in the near-infrared region that can transform near-infrared light into localised heat with fewer side effects, provide easier integration with existing therapies, and offer increased effectiveness. They have been combined with photothermal therapy to understand the chemical and physical activities behind the stimuli-responsiveness of polymer nanomaterials. In this review article, we provide detailed information regarding the recent advances in polymer nanomaterials for the non-invasive photothermal treatment of arthritis. The synergistic effect of polymer nanomaterials and photothermal therapy has enhanced the treatment and diagnosis of arthritis and reduced the side effects of drugs in the joint cavity. In addition, further novel challenges and future perspectives must be resolved to advance polymer nanomaterials for the photothermal therapy of arthritis.
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The aim of this study was to design, optimize, and develop metronidazole (Met) loaded nanoparticles (MetNp) by employing quality-based design (QbD) as well as a risk assessment methodology. A fractional factorial design was used by selecting five independent variables viz., chitosan concentration, tripolyphosphate concentration, and acetic acid concentration as material attributes, stirring speed, and stirring time as process parameters, whereby their influence on two dependent variables such as particle size (PS) and %entrapment efficiency (%EE) was studied. MetNp were synthesized by employing an ionic-gelation technique and optimized formula obtained from the QbD design study. PS and %EE studies revealed the formation of MetNp with 558.06 ± 2.52 nm and 59.07 ± 2.15%, respectively. Furthermore, a Met release study in various simulated gastro-intestinal media suggested pH-triggered (pH > 7.0) and sustained release profile of Met from Eudragit S100 enteric-coated MetNp capsule (MetNp cap). Moreover, the stability investigation of formulations confirmed good stability with respect to their PS and residual drug content (RDC) at different temperature conditions. In conclusion, the QbD method was effectively utilized in the development of MetNp and enteric-coated MetNp cap depicting their potential to release Met through MetNp cap only in the colon region and can be utilized for the treatment of amoebiasis in the colon.
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Etoposide (ETS), topoisomerase-II inhibitor, is a first-line anticancer therapeutics used in diverse cancer types. However, the therapeutic potential of this molecule has mainly impeded due to its detrimental toxicity profile, unfavorable rejection by the cancer cells due to P-glycoprotein (P-gp) efflux activity, and rapid hepatic clearance through extensive metabolism by Cytochrome-P450. To increase the therapeutic potency without significant adverse effects, the implication of novel ETS-nanoformulation strategies have recommended mainly. Nanomedicine based nanoformulation approaches based on nanoparticles (NPs), dendrimers, carbon-nanotubes (CNTs), liposomes, polymeric micelles, emulsions, dendrimers, solid-lipid NPs, etc offers immense potential opportunities to improve the therapeutic potential of pharmaceutically problematic drugs. This review provides an up-to-date argument on the work done in the field of nanomedicine to resolve pharmacokinetic and pharmacodynamic issues associated with ETS. The review also expounds the progress in regards to the regulatory, patenting and clinical trials related to the innovative formulation aspects of ETS.
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Portadores de Fármacos/química , Etopósido/química , Nanopartículas/química , Inhibidores de Topoisomerasa II/química , Animales , Estabilidad de Medicamentos , Endocitosis , Etopósido/metabolismo , Semivida , Humanos , Solubilidad , Inhibidores de Topoisomerasa II/metabolismoRESUMEN
BACKGROUND: Prostate cancer (PC) has the highest prevalence in men and accounts for a high rate of neoplasia-related death. Doxorubicin (DOX) is one of the most widely used anti-neoplastic drugs for prostate cancer among others. However, it has low specificity and many side effects and affects normal cells. More recently, there have been newly developed drug delivery tools which are graphene or graphene-based, used to increase the specificity of the delivered drug molecules. The graphene derivatives possess both π-π stacking and increased hydrophobicity, factors that increase the likelihood of drug delivery. Despite this, the hydrophilicity of graphene remains problematic, as it induced problems with stability. For this reason, the use of a chitosan coating remains one way to modify the surface features of graphene. METHOD: In this investigation, a hybrid nanoparticle that consisted of a DOX-loaded reduced graphene oxide that is stabilized with chitosan (rGOD-HNP) was developed. RESULT: The newly developed rGOD-HNP demonstrated high biocompatibility and efficiency in entrapping DOX (~65%) and releasing it in a controlled manner (~50% release in 48 h). Furthermore, it was also demonstrated that rGOD-HNP can intracellularly deliver DOX and more specifically in PC-3 prostate cancer cells. CONCLUSION: This delivery tool offers a feasible and viable method to deliver DOX photo-thermally in the treatment of prostate cancer.
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Doxorrubicina/uso terapéutico , Grafito/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Grafito/síntesis química , Hemólisis/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Ratones , Oxidación-Reducción , Espectroscopía Infrarroja por Transformada de Fourier , TemperaturaRESUMEN
RNA interference (RNAi) therapeutics (siRNA, miRNA, etc.) represent an emerging medicinal remedy for a variety of ailments. However, their low serum stability and low cellular uptake significantly restrict their clinical applications. Exosomes are biologically derived nanodimensional vesicle ranging from a few nanometers to a hundred. In the last few years, several reports have been published demonstrating the emerging applications of these exogenous membrane vesicles, particularly in carrying different RNAi therapeutics to adjacent or distant targeted cells. In this report, we explored the numerous aspects of exosomes from structure to clinical implications with special emphasis on their application in delivering RNAi-based therapeutics. siRNA and miRNA have attracted great interest in recent years due to their specific application in treating many complex diseases including cancer. We highlight strategies to obviate the challenges of their low bioavailability for gene therapy.
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Exosomas/química , Terapia Genética/métodos , Nanocápsulas/química , Neoplasias/terapia , Interferencia de ARN , Animales , Técnicas de Transferencia de Gen , Humanos , MicroARNs/metabolismo , Neoplasias/genética , ARN Interferente Pequeño/metabolismo , Tratamiento con ARN de Interferencia/métodosRESUMEN
BACKGROUND: Nifedipine is a potential therapeutic agent for the treatment of cardiovascular disturbances, although it suffers from short half-life (t1/2, 2 hr). OBJECTIVE: To address the problem, we first prepared nifedipine loaded sustained release microsponges and then formulated tablets for effective clinical application and patient compliance. METHOD: Preparations of microsponges were carried out using different compositions of nifedipine and polymer (1:1, 1:2 and 1:3 % molar ratio) using emulsion solvent diffusion technique. RESULTS: The microsponges with molar ratio 1:3 (formulation code: MF-3) found optimized as revealed by analyzing surface morphology, better powder flow properties (angle of repose; 28.80 ± 0.9, Hausner ratio 1.15 ± 0.2, % compressibility 15.28 ± 0.5% and higher % drug content (80 ± 1.9 %). Different batches of tablets were then formulated incorporating MF-3 microsponges and different proportions (10-50 %) of microcrystalline cellulose and starch as additives. Among tablet formulations, batch composed of 48% of MF-3, 30% of MCC, 20 % of starch and 2 % of talc (TF-33), showed 92.73 ± 2.19 % drug release during 24 hr in vitro release study in comparison to other batches including commercial formulation which was found to be released completely in 20 hr. Further, stability analysis revealed good drug retention of loaded nifedipine as well as consistent in vitro release pattern over a period of 90 days at 40°C and 75% RH. CONCLUSION: The microsponge tablet delivery system was found to be superior concerning the therapeutic advantage as well as manufacturing feasibility of nifedipine.
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Antihipertensivos/química , Composición de Medicamentos/métodos , Nifedipino/química , Polímeros/química , Antihipertensivos/administración & dosificación , Preparaciones de Acción Retardada , Liberación de Fármacos , Estabilidad de Medicamentos , Emulsiones , Semivida , Humanos , Nifedipino/administración & dosificación , Tamaño de la Partícula , Solubilidad , ComprimidosRESUMEN
BACKGROUND: The respiratory tract as a non-invasive route of drug administration is gaining increasing attention in the present time on achieving both local and the systemic therapeutic effects. Success in achieving pulmonary delivery, requires overcoming barriers including mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time and rate to target sites. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically. METHODS: We searched and reviewed the literature focusing on chitosan and chitosan derivative based nanocarrier systems used in pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for this purpose. RESULTS: Chitosan, a natural linear bio-polyaminosaccharide is central in the development of novel drug delivery systems (NDDS) including nanoparticles for use in the treatment of various respiratory diseases. It achieves this through its unique properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation across membranes. It also achieves sustained and targeted effects, primary requirements for an effective pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, employed in the management of respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. CONCLUSION: This review will be of interest to both the biological and formulation scientists as it provides a summary on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available for pulmonary drug delivery and so this area has enormous potential in the field of respiratory science.
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Quitosano/análogos & derivados , Quitosano/química , Portadores de Fármacos/química , Trastornos Respiratorios/tratamiento farmacológico , Animales , Asma/tratamiento farmacológico , Preparaciones de Acción Retardada , Liberación de Fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Fibrosis Pulmonar/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológicoRESUMEN
BACKGROUND: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients. METHODS: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body. RESULTS: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation. CONCLUSION: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.
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Dendrímeros/uso terapéutico , Neoplasias/tratamiento farmacológico , Dendrímeros/administración & dosificación , Dendrímeros/síntesis química , Dendrímeros/química , Humanos , Metástasis de la Neoplasia , Neoplasias/patologíaRESUMEN
To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth. Here, we review the use of dendritic delivery systems in tissue engineering. We discuss the available literature, highlighting the 3D architecture and preparation of these nanoscaffolds, and also review challenges to, and advances in, the use dendrimers in tissue engineering. Advances in the manufacturing of dendritic nanoparticles and scaffold architectures have resulted in the successful incorporation of dendritic scaffolds in tissue engineering.
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Dendrímeros/uso terapéutico , Nanopartículas/administración & dosificación , Animales , Materiales Biocompatibles/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Humanos , Regeneración/efectos de los fármacos , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
The merger of nanotechnology and combination chemotherapy has shown notable promise in the therapy of resistant tumors. The latest scientific attention encompasses the engagement of anticancer drugs in combination with small interfering (si)RNAs, such as VEGF, XLAP, PGP, MRP-1, BCL-2 and cMyc, to name but a few. siRNAs have shown immense promise to knockout drug resistance genes as well as to recover the sensitivity of resistant tumors to anticancer therapy. The nanotechnology approach could also protect siRNA against RNAse degradation as well as prevent off-target effects. In this article, we discuss the approaches that have been used to deliver of siRNA in combination with chemotherapeutic drugs to treat resistant tumors. We also discuss the stipulations that must be considered in formulating a nanotechnology-assisted siRNA-drug cancer therapy.
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Antineoplásicos/administración & dosificación , Neoplasias/terapia , Interferencia de ARN , ARN Interferente Pequeño/administración & dosificación , Animales , Terapia Combinada , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos , Humanos , NanotecnologíaRESUMEN
In this investigation, sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product. The method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18 columns (1.7 µm, 2.1 mm × 150 mm) using acetonitrile and water (40:60 V/V) at a flow rate of 0.2 mL/minute in UPLC. UV detection was performed at 240.1 nm. Deflazacort was subjected to oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The drug was found to be stable in water and thermal stress, as well as under neutral stress conditions. However, forced-degradation study performed on deflazacort showed that the drug degraded under alkaline, acid and photolytic stress. The degradation products were well resolved from the main peak, which proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to accuracy, linearity, limit of detection, limit of quantification, accuracy, precision and robustness, selectivity and specificity. Apart from the aforementioned, the results of the present study also emphasize the importance of isolation characterization and identification of degradant. Hence, an attempt was made to identify the degradants in deflazacort. One of the degradation products of deflazacort was isolated and identified by the FTIR, NMR and LC-MS study.
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Cardiovascular diseases (CVDs), primarily myocardial infarction (MI), atherosclerosis, hypertension and congestive heart failure symbolize the foremost cause of death in almost all parts of the world. Besides the traditional therapeutic approaches for the management of CVDs, newer innovative strategies are also emerging on the horizon. Recently, gene silencing via small interfering RNA (siRNA) is one of the hot topics amongst various strategies involved in the management of CVDs. The siRNA mechanism involves natural catalytic processes to silence pathological genes that are overexpressed in a particular disease. Also the versatility of gene expression by siRNA deciphers a prospective tactic to down-regulate diseases associated gene, protein or receptor existing on a specific disease target. This article reviews the application of siRNA against CVDs with special emphasis on gene targets in combination with delivery systems such as cationic hydrogels, polyplexes, peptides, liposomes and dendrimers.
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Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/terapia , Portadores de Fármacos/química , Terapia Genética/métodos , Nanopartículas/química , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Silenciador del Gen , Humanos , NanotecnologíaRESUMEN
siRNA technology presents a helpful means of gene silencing in mammalian cells. Advancement in the field includes enhanced attentiveness in the characterization of target and off-target effects employing suitable controls and gene expression microarrays. These will permit expansion in the measurement of single and multiple target combinations and also permit comprehensive efforts to understand mammalian cell processes. Another fact is that the delivery of siRNA requires the creation of a nanoparticulate vector with controlled structural geometry and surface modalities inside the targeted cells. On the other hand, dendrimers represent the class of carrier system where massive control over size, shape and physicochemical properties makes this delivery vector exceptional and favorable in genetic transfection applications. The siRNA therapeutics may be incorporated inside the geometry of the density controlled dendrimers with the option of engineering the structure to the specific needs of the genetic material and its indication. The existing reports on the siRNA carrying and deliverance potential of dendrimers clearly suggest the significance of this novel class of polymeric architecture and certainly elevate the futuristic use of this highly branched vector as genetic material delivery system.
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Dendrímeros/química , Silenciador del Gen , ARN Interferente Pequeño/administración & dosificación , Animales , Técnicas de Transferencia de Gen , Vectores Genéticos , Humanos , Nanopartículas , Polímeros/química , Interferencia de ARNRESUMEN
The increasing prevalence and complexity of cardiovascular diseases demand innovative strategies for diagnostic and therapeutic applications to improve patient care/prognoses. Additionally, various factors constrain present cardiovascular therapies, including low aqueous drug solubility, early metabolism, short half-life and drug delivery limitations. The efficient treatment of cardiovascular diseases requires improvement of traditional drug delivery systems. This can be accomplished by using novel nanomaterial that can incorporate diverse bio-actives along with diagnostic agents in a single carrier, referred to as theranostics. This review discusses the state of the art in the applications to diagnosis and therapy of innovative, nanomaterial- based strategies such as lipid based carriers, nanocapsules, magnetic nanoparticles, gold nanoparticles, protein conjugated nanoparticles, dendrimers and carbon-based nanoformulations with a special emphasis on how they can contribute to improving the management of cardiovascular disease.
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Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/tratamiento farmacológico , Nanomedicina , Nanopartículas/química , Portadores de Fármacos/química , HumanosRESUMEN
PURPOSE: To formulate dendrimer-stabilized smart-nanoparticle (DSSN; pD-ANP-f) for the targeted delivery of the highly hydrophobic anticancer drug, Paclitaxel (PTXL). METHOD: The developed nanoformulations were evaluated for particle size, surface-charge, loading efficiency, particle density, in-vitro drug release, SEM/TEM, cytotoxicity assay, fluorescence uptake, HPLC quantitative cell uptake assay, flow cytometry, tubulin polymerization, and stability assessments. RESULTS: The developed pD-ANP-f nanoformulation (135.17 ± 7.39 nm; -2.05 ± 0.37 mV and 80.11 ± 4.39% entrapment) exhibited a pH-dependent drug release; remained stable in physiological pH, while rapid releasing PTXL under tumorous environment (pH 5.5). The cytotoxicity assay performed in cervical, breast, blood, and liver cancer cell lines showed pD-ANP-f to be strongly suppressing the growth of cancer cells. We investigated the fluorescence based intracellular trafficking and HPLC based cellular uptake of nanoformulated drug and the result indicates higher cellular uptake of pD-ANP-f compared to other formulations. pD-ANP-f prominently induced apoptosis (73.11 ± 3.84%) and higher polymerization of tubulins (59.73 ± 6.22%). DSSN nanoformulation was found to be extremely biocompatible (<1% hemolytic) compared to naked PTXL (19.22 ± 1.01%) as well as PTXL-dendrimer nanocomplex (8.29 ± 0.71%). CONCLUSION: DSSN strategy is a novel and promising platform for biomedical applications that can be effectively engaged for the delivery of drug/gene/siRNA targeting.