RESUMO
We have synthesized, characterized, and optimized a novel nano drug-delivery carrier that utilizes the versatile properties of nucleic acid for programmable and on-demand drug release. The drug-delivery carrier consists of 15 nm gold nanoparticles (AuNPs) functionalized with drug binding DNA aptamers via single-stranded (ss) anchor DNA. The presence of anchor DNA makes the nanocarrier flexible to be reprogrammed with various aptamers. Under the optimum binding conditions (0.4 M NaCl and 4 µM DNA), a maximum of 101 ± 8 anchor DNA strands were conjugated per particle. On binding DNA-aptamer:drug complexes to AuNPs, a maximum of 35 neomycin molecules were bound per AuNP. Controlled and extended release of drug from the synthesized carrier was obtained by temperature and affinity modulations. Furthermore, for the first time, we demonstrated that neomycin could bind to DNA with very high affinity (K(d) = 98.101 nM). This DNA-based nanocarrier, designed using the principles of molecular biology, is expected to impact a number of treatment strategies. FROM THE CLINICAL EDITOR: In this basic science work, the authors demonstrate the feasibility of utilizing a novel nano drug-delivery carrier with the versatile properties of nucleic acid for programmable and on-demand drug release.
Assuntos
Antibacterianos/administração & dosagem , Aptâmeros de Nucleotídeos/química , Preparações de Ação Retardada/química , Ouro/química , Nanopartículas/química , Neomicina/administração & dosagem , Aptâmeros de Nucleotídeos/metabolismo , Sítios de LigaçãoRESUMO
CONTEXT: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. AIM: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. SUBJECTS AND METHODS: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. STATISTICAL ANALYSIS USED: Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. RESULTS: Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). CONCLUSION: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.
RESUMO
Therapeutics such as nucleic acids, proteins/peptides, vaccines, anti-cancer, and other drugs have disadvantages of low bio-availability, rapid clearance, and high toxicity. Thus, there is a significant need for the development of efficient delivery methods and carriers. Injectable nanocarriers have received much attention due to their vast range of structures and ability to contain multiple functional groups, both within the bulk material and on the surface of the particles. Nanocarriers may be tailored to control drug release and/or increase selective cell targeting, cellular uptake, drug solubility, and circulation time, all of which lead to a more efficacious delivery and action of therapeutics. The focus of this review is injectable, targeted nanoparticle drug delivery carriers highlighting the diversity of nanoparticle materials and structures as well as highlighting current therapeutics and targeting moieties. Structures and materials discussed include liposomes, polymersomes, dendrimers, cyclodextrin-containing polymers (CDPs), carbon nanotubes (CNTs), and gold nanoparticles. Additionally, current clinical trial information and details such as trial phase, treatment, active drug, carrier sponsor, and clinical trial identifier for different materials and structures are presented and discussed.
Assuntos
Portadores de Fármacos/administração & dosagem , Nanoestruturas/administração & dosagem , Animais , Ensaios Clínicos como Assunto/métodos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Injeções , Lipossomos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológicoRESUMO
RNA aptamers can fold into complex structures and bind with high affinity and selectivity to various macromolecules, viruses, and cells. They are isolated from a large pool of nucleic acids by a conceptually straightforward iterative selection process called SELEX. Aptamers have enormous potential as therapeutics due to their ability to bind to proteins and specifically inhibit their functions with minimal or no harmful side-effects. The first aptamer therapeutic was FDA approved in 2005 and a number of novel aptamer-based therapeutics are currently undergoing clinical trials for treating diseases such as macular degeneration, choroidal neovascularization, intravascular thrombus, acute coronary syndrome, von Willebrand factor related disorders, von Hippel-Lindau syndrome (VHL), angiomas, acute myeloid leukemia, renal cell carcinoma, non-small cell lung cancer, thrombotic thrombocytopenic purpura, and several others. In this review, we present aptamers in on-going, completed, and terminated clinical studies highlighting their mechanism of action as well as the inherent challenges of aptamer production and use.
Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemostasia , Humanos , Degeneração Macular/tratamento farmacológico , Neoplasias/tratamento farmacológicoRESUMO
We describe the design and implementation of a high-data-rate high-capacity digital holographic storage disk system. Various system design trade-offs that affect density and data-rate performance are described and analyzed. In the demonstration system that we describe, high-density holographic recording is achieved by use of high-resolution short-focal-length optics and correlation shift multiplexing in photopolymer disk media. Holographic channel decoding at a 1-Gbit/s data rate is performed by custom-built electronic hardware. A benchmark sustained optical data-transfer rate of 10 Gbits/s has been successfully demonstrated.