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1.
PLoS One ; 19(2): e0299334, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422084

RESUMO

This research addresses the pressing challenge of intrusion detection and prevention in Wireless Sensor Networks (WSNs), offering an innovative and comprehensive approach. The research leverages Support Vector Regression (SVR) models to predict the number of barriers necessary for effective intrusion detection and prevention while optimising their strategic placement. The paper employs the Ant Colony Optimization (ACO) algorithm to enhance the precision of barrier placement and resource allocation. The integrated approach combines SVR predictive modelling with ACO-based optimisation, contributing to advancing adaptive security solutions for WSNs. Feature ranking highlights the critical influence of barrier count attributes, and regularisation techniques are applied to enhance model robustness. Importantly, the results reveal substantial percentage improvements in model accuracy metrics: a 4835.71% reduction in Mean Squared Error (MSE) for ACO-SVR1, an 862.08% improvement in Mean Absolute Error (MAE) for ACO-SVR1, and an 86.29% enhancement in R-squared (R2) for ACO-SVR1. ACO-SVR2 has a 2202.85% reduction in MSE, a 733.98% improvement in MAE, and a 54.03% enhancement in R-squared. These considerable improvements verify the method's effectiveness in enhancing WSNs, ensuring reliability and resilience in critical infrastructure. The paper concludes with a performance comparison and emphasises the remarkable efficacy of regularisation. It also underscores the practicality of precise barrier count estimation and optimised barrier placement, enhancing the security and resilience of WSNs against potential threats.


Assuntos
Algoritmos , Resiliência Psicológica , Reprodutibilidade dos Testes , Benchmarking , Alocação de Recursos
2.
Environ Sci Technol ; 57(46): 18091-18103, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37399541

RESUMO

CO2 sorption in physical solvents is one of the promising approaches for carbon capture from highly concentrated CO2 streams at high pressures. Identifying an efficient solvent and evaluating its solubility data at different operating conditions are highly essential for effective capture, which generally involves expensive and time-consuming experimental procedures. This work presents a machine learning based ultrafast alternative for accurate prediction of CO2 solubility in physical solvents using their physical, thermodynamic, and structural properties data. First, a database is established with which several linear, nonlinear, and ensemble models were trained through a systematic cross-validation and grid search method and found that kernel ridge regression (KRR) is the optimum model. Second, the descriptors are ranked based on their complete decomposition contributions derived using principal component analysis. Further, optimum key descriptors (KDs) are evaluated through an iterative sequential addition method with the objective of maximizing the prediction accuracy of the reduced order KRR (r-KRR) model. Finally, the study resulted in the r-KRR model with nine KDs exhibiting the highest prediction accuracy with a minimum root-mean-square error (0.0023), mean absolute error (0.0016), and maximum R2 (0.999). Also, the validity of the database created and ML models developed is ensured through detailed statistical analysis.


Assuntos
Dióxido de Carbono , Aprendizado de Máquina , Dióxido de Carbono/química , Solventes/química
3.
Phys Rev E ; 107(6-1): 064118, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37464618

RESUMO

Renormalization enables a systematic scale-by-scale analysis of multiscale systems. In this paper, we employ renormalization group (RG) to the shell model of turbulence and show that the RG equation is satisfied by |u_{n}|^{2}=K_{Ko}ε^{2/3}k_{n}^{-2/3}, where Ko is the Kolmogorov constant and ν_{n}=ν_{*}sqrt[K_{Ko}]ε^{1/3}k_{n}^{-4/3}, where k_{n}andu_{n} are the wave number and velocity of shell n; ν_{*}andK_{Ko} are RG and Kolmogorov's constants; and ε is the energy dissipation rate. We find that ν_{*}≈0.5 and K_{Ko}≈1.7, consistent with earlier RG works on the Navier-Stokes equation. We verify the theoretical predictions using numerical simulations.

4.
Phys Rev E ; 107(5-2): 055106, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37329061

RESUMO

In this paper, using a shell model, we simulate highly turbulent stably stratified flow for weak to moderate stratification at unitary Prandtl number. We investigate the energy spectra and fluxes of velocity and density fields. We observe that for moderate stratification, in the inertial range, the kinetic energy spectrum E_{u}(k) and the potential energy spectrum E_{b}(k) show dual scaling-Bolgiano-Obukhov scaling [E_{u}(k)∼k^{-11/5} and E_{b}(k)∼k^{-7/5}] for kk_{B}. In addition, we find that the mixing efficiency η_{mix} varies as η_{mix}∼Ri for weak stratification, whereas η_{mix}∼Ri^{1/3} for moderate stratification, where Ri is the Richardson number.

5.
Sensors (Basel) ; 23(11)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37300076

RESUMO

The emergence of the Internet of Things (IoT) and its subsequent evolution into the Internet of Everything (IoE) is a result of the rapid growth of information and communication technologies (ICT). However, implementing these technologies comes with certain obstacles, such as the limited availability of energy resources and processing power. Consequently, there is a need for energy-efficient and intelligent load-balancing models, particularly in healthcare, where real-time applications generate large volumes of data. This paper proposes a novel, energy-aware artificial intelligence (AI)-based load balancing model that employs the Chaotic Horse Ride Optimization Algorithm (CHROA) and big data analytics (BDA) for cloud-enabled IoT environments. The CHROA technique enhances the optimization capacity of the Horse Ride Optimization Algorithm (HROA) using chaotic principles. The proposed CHROA model balances the load, optimizes available energy resources using AI techniques, and is evaluated using various metrics. Experimental results show that the CHROA model outperforms existing models. For instance, while the Artificial Bee Colony (ABC), Gravitational Search Algorithm (GSA), and Whale Defense Algorithm with Firefly Algorithm (WD-FA) techniques attain average throughputs of 58.247 Kbps, 59.957 Kbps, and 60.819 Kbps, respectively, the CHROA model achieves an average throughput of 70.122 Kbps. The proposed CHROA-based model presents an innovative approach to intelligent load balancing and energy optimization in cloud-enabled IoT environments. The results highlight its potential to address critical challenges and contribute to developing efficient and sustainable IoT/IoE solutions.


Assuntos
Algoritmos , Inteligência Artificial , Animais , Cavalos , Inteligência , Conscientização , Internet
6.
Cureus ; 15(4): e37774, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37213948

RESUMO

Hypertension is a risk factor for cardiovascular diseases which also causes progressive kidney damage leading to chronic kidney disease (CKD), so the rate of progression of CKD can be controlled by reducing blood pressure (BP). Many anti-hypertensive drugs are available. Cilnidipine is a new-generation calcium channel blocker (CCB). This meta-analysis is aimed to generate pooled evidence about the effectiveness of cilnidipine as an anti-hypertensive and to explore its reno-protective actions. Pubmed, Scopus, Cochrane Library, and Google Scholar were searched from January 2000 to December 2022 to include the studies. The pooled mean difference, along with 95% CI, was computed using Revman 5.4.1 software (Revman International, Inc., New York City, New York). The Cochrane risk-of-bias assessment tool was used for bias assessment. This meta-analysis was registered in PROSPERO with Reg. no. CRD42023395224. This meta-analysis included seven studies with 289 participants in the intervention group and 269 in the comparator group, and were selected from Japan, India, and Korea. Systolic blood pressure (SBP) was significantly reduced in cilnidipine treated group among hypertensives with CKD subjects weighted mean difference (WMD) was 4.33, and the 95% confidence interval (CI) was 1.26 to 7.31 as compared to the other group. Cilnidipine also shows a significant reduction in proteinuria with WMD 0.61 and 95% CI 0.42 to 0.80. Both groups were similar in adverse drug reactions (ADR). Cilnidipine is a more effective anti-hypertensive as compared to Amlodipine or other CCBs, mainly in reducing SBP. Besides this, cilnidipine also shows better reno-protective action because it also significantly reduces proteinuria in such patients.

7.
Macromol Biosci ; 22(9): e2200097, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35920099

RESUMO

Wound healing is a complex process requiring multiple biological pathways and chemical responses to be activated and synchronized to recover tissue integrity. In normal physiological circumstances, the epidermal barrier restoration process through new tissue formation is highly efficient. However, increased production of reactive oxygen species (ROS), attack of pathogenic microorganisms, and high glucose level delay the normal healing process in diabetic patients. The successful treatment of diabetic wounds requires efficient strategies to control oxidative stress, promoting angiogenesis, re-epithelialization, and collagen deposition. In this study, a composite hydrogel for rapid wound healing in diabetic condition is developed by the amalgamation of hypolipidemic property of silk fibroin (SF), antioxidant property of melanin, and therapeutic effect of berberine. Studies have revealed that cross-linked mesoporous morphology of hydrogel matrix facilitates slow release of berberine to impart long-term therapeutic effects at wound site. The composite hydrogel formulation is biocompatible, stimulates effective migration of fibroblast cells, and control oxidative stress under in vitro conditions. The hydrogel served as scaffold for tissue re-epithelialization and promotes wound repair in diabetic type I Wistar rat model. This study demonstrates the ability of berberine- loaded SF-melanin composite hydrogel as a potential dressing formulation for wound healing in diabetic conditions.


Assuntos
Berberina , Diabetes Mellitus , Fibroínas , Animais , Antioxidantes/farmacologia , Berberina/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Melaninas , Ratos , Ratos Wistar , Seda/farmacologia , Cicatrização
8.
Comput Intell Neurosci ; 2022: 9766844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634070

RESUMO

The internet of medical things (IoMT) is a smart medical device structure that includes apps, health services, and systems. These medical equipment and applications are linked to healthcare systems via the internet. Because IoT devices lack computational power, the collected data can be processed and analyzed in the cloud by more computationally intensive tools. Cloud computing in IoMT is also used to store IoT data as part of a collaborative effort. Cloud computing has provided new avenues for providing services to users with better user experience, scalability, and proper resource utilization compared to traditional platforms. However, these cloud platforms are susceptible to several security breaches evident from recent and past incidents. Trust management is a crucial feature required for providing secure and reliable service to users. The traditional trust management protocols in the cloud computing situation are centralized and result in single-point failure. Blockchain has emerged as the possible use case for the domain that requires trust and reliability in several aspects. Different researchers have presented various blockchain-based trust management approaches. This study reviews the trust challenges in cloud computing and analyzes how blockchain technology addresses these challenges using blockchain-based trust management frameworks. There are ten (10) solutions under two broad categories of decentralization and security. These challenges are centralization, huge overhead, trust evidence, less adaptive, and inaccuracy. This systematic review has been performed in six stages: identifying the research question, research methods, screening the related articles, abstract and keyword examination, data retrieval, and mapping processing. Atlas.ti software is used to analyze the relevant articles based on keywords. A total of 70 codes and 262 quotations are compiled, and furthermore, these quotations are categorized using manual coding. Finally, 20 solutions under two main categories of decentralization and security were retrieved. Out of these ten (10) solutions, three (03) fell in the security category, and the rest seven (07) came under the decentralization category.


Assuntos
Blockchain , Computação em Nuvem , Internet , Reprodutibilidade dos Testes , Confiança
9.
Front Public Health ; 10: 858327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372222

RESUMO

Early detection of vessels from fundus images can effectively prevent the permanent retinal damages caused by retinopathies such as glaucoma, hyperextension, and diabetes. Concerning the red color of both retinal vessels and background and the vessel's morphological variations, the current vessel detection methodologies fail to segment thin vessels and discriminate them in the regions where permanent retinopathies mainly occur. This research aims to suggest a novel approach to take the benefit of both traditional template-matching methods with recent deep learning (DL) solutions. These two methods are combined in which the response of a Cauchy matched filter is used to replace the noisy red channel of the fundus images. Consequently, a U-shaped fully connected convolutional neural network (U-net) is employed to train end-to-end segmentation of pixels into vessel and background classes. Each preprocessed image is divided into several patches to provide enough training images and speed up the training per each instance. The DRIVE public database has been analyzed to test the proposed method, and metrics such as Accuracy, Precision, Sensitivity and Specificity have been measured for evaluation. The evaluation indicates that the average extraction accuracy of the proposed model is 0.9640 on the employed dataset.


Assuntos
Algoritmos , Vasos Retinianos/diagnóstico por imagem , Fundo de Olho , Humanos , Redes Neurais de Computação , Vasos Retinianos/anatomia & histologia
10.
Mater Today Proc ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33777707

RESUMO

The refugees and migrants are not recorded generally and deemed invisible by governments without providing them with identity and welfare services. The COVID-19 pandemic has badly impacted the economy, and the poor migrants and refugees have suffered most due to the closure of industries and informal sectors. Lack of legal identity made them more vulnerable and excluded them from getting benefits of even meagre government support and welfare schemes. Self-sovereign identity is a form of distributed digital identity that can provide immutable identity with full user control and interoperability features. Self-sovereign identities also ensure the privacy and security of personal information. SSI model can effectively provide migrants and refugees with an effective legal identity and include them in government welfare schemes and other schemes run by non-governmental agencies. Also, SSI can be used for uniquely identifying the people who have been already vaccinated or tested negative from COVID-19 within a stipulated time. This paper reviews the aspects of SSI application during the pandemic situation like COVID-19.

11.
ACS Appl Bio Mater ; 3(6): 3544-3552, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35025224

RESUMO

Diabetes is a chronic disease affecting over 400 million people worldwide. Inadequate production of insulin due to loss of beta cells or insulin resistance within the body imbalances the glucose homeostasis, resulting in an abrupt increase of blood glucose level. The conventional and last resort of treatment involves repeated subcutaneous insulin injections to maintain the physiological glucose homeostasis. However, continuous and multiple subcutaneous injections are associated with poor patient compliance and local amyloidosis of insulin, which can be overcome with controlled and sustained insulin delivery. In this context, we have designed and formulated an injectable silk fibroin hydrogel (iSFH) to realize sustained insulin delivery over a prolonged period under diabetic conditions. The specific composition of glycol additives (ethylene glycol and triethylene glycol) allowed the silk fibroin protein to form an injectable hydrogel within 50 min. The detailed characterization of iSFH by a field-emission scanning electron microscope displayed the desired mesoporous structures, which are appropriate for drug (insulin) encapsulation in its active form. Interestingly, the subcutaneous injection of iSFH-encapsulated insulin (insulin-iSFH) in diabetic T1DM Wistar rats showed controlled release of insulin and restored physiological glucose homeostasis up to 4 days. The biocompatible and biodegradable nature of iSFH makes it a potential drug delivery system for active storage, and controlled and sustained delivery of insulin in diabetic conditions to maintain the physiological glucose level.

12.
ACS Omega ; 3(6): 6912-6930, 2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30023966

RESUMO

Despite the vast availability of antibiotics, bacterial infections remain a leading cause of death worldwide. In an effort to enhance the armamentarium against resistant bacterial strains, 1,2,3-triazole (5a-x) and sulfonate (7a-j) analogues of natural bioactive precursors were designed and synthesized. Preliminary screening against two Gram-positive (Streptococcus pneumoniae and Enterococcus faecalis) and four Gram-negative bacterial strains (Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Escherichia coli) was performed to assess the potency of these analogues as antibacterial agents. Among all triazole analogues, 5e (derived from carvacrol) and 5u (derived from 2-hydroxy 1,4-naphthoquinone) bearing carboxylic acid functionality emerged as potent antibacterial agents against S. pneumoniae (IC50: 62.53 and 39.33 µg/mL), E. faecalis (IC50: 36.66 and 61.09 µg/mL), and E. coli (IC50: 15.28 and 22.57 µg/mL). Furthermore, 5e and 5u also demonstrated moderate efficacy against multidrug-resistant E. coli strains and were therefore selected for further biological studies. Compound 5e in combination with ciprofloxacin displayed a synergistic effect on multidrug-resistant E. coli MRA11 and MRC17 strains, whereas compound 5u was selective against E. coli MRA11 strain. Growth kinetic studies on S. pneumoniae and E. coli treated with 5e and 5u showed an extended lag phase. 5e and 5u did not show significant cytotoxicity up to 100 µg/mL concentration on human embryonic kidney (HEK293) cells. Transmission electron microscopic (TEM) analysis of bacterial cells (S. pneumoniae and E. coli) exposed to 5e and 5u clearly showed morphological changes and damaged cell walls. Moreover, these compounds also significantly inhibited biofilm formation in S. pneumoniae and E. coli strains, which was visualized by scanning electron microscopic (SEM) analysis. Treatment of larvae of Galleria mellonella (an in vivo model for antimicrobial studies) with 5e and 5u did not cause an alteration in the hemocyte density, thereby indicating lack of an immune response, and were nontoxic up to a concentration of 2.5 mg/mL.

13.
PLoS One ; 12(4): e0175710, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28430797

RESUMO

Candida albicans, along with some other non-albicans Candida species, is a group of yeast, which causes serious infections in humans that can be both systemic and superficial. Despite the fact that extensive efforts have been put into the discovery of novel antifungal agents, the frequency of these fungal infections has increased drastically worldwide. In our quest for the discovery of novel antifungal compounds, we had previously synthesized and screened quinoline containing 1,2,3-triazole (3a) as a potent Candida spp inhibitor. In the present study, two structural analogues of 3a (3b and 3c) have been synthesized to determine the role of quinoline and their anti-Candida activities have been evaluated. Preliminary results helped us to determine 3a and 3b as lead inhibitors. The IC50 values of compound 3a for C. albicans ATCC 90028 (standard) and C. albicans (fluconazole resistant) strains were 0.044 and 2.3 µg/ml, respectively while compound 3b gave 25.4 and 32.8 µg/ml values for the same strains. Disk diffusion, growth and time kill curve assays showed significant inhibition of C. albicans in the presence of compounds 3a and 3b. Moreover, 3a showed fungicidal nature while 3b was fungistatic. Both the test compounds significantly lower the secretion of proteinases and phospholipases. While, 3a inhibited proteinase secretion in C. albicans (resistant strain) by 45%, 3b reduced phospholipase secretion by 68% in C. albicans ATCC90028 at their respective MIC values. Proton extrusion and intracellular pH measurement studies suggested that both compounds potentially inhibit the activity of H+ ATPase, a membrane protein that is crucial for various cell functions. Similarly, 95-97% reduction in ergosterol content was measured in the presence of the test compounds at MIC and MIC/2. The study led to identification of two quinoline based potent inhibitors of C. albicans for further structural optimization and pharmacological investigation.


Assuntos
Candida albicans/efeitos dos fármacos , Quinolinas/química , Triazóis/farmacologia , Candida albicans/crescimento & desenvolvimento , Candida albicans/patogenicidade , Testes de Sensibilidade Microbiana , Triazóis/química , Virulência/efeitos dos fármacos
14.
J Nanobiotechnology ; 14: 26, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-27044333

RESUMO

BACKGROUND: Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine-α,ß-dehydrophenylalanine (FΔF), arginine-α,ß-dehydrophenylalanine (RΔF), valine-α,ß-dehydrophenylalanine (VΔF) and methonine-α,ß-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. RESULTS: FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC50, 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC50, 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nanoparticles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells. CONCLUSION: This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an enhancement in its efficacy as an antimalarial agent.


Assuntos
Antimaláricos/farmacologia , Curcumina/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Malária/tratamento farmacológico , Nanopartículas/administração & dosagem , Animais , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Nanotubos de Peptídeos , Plasmodium falciparum/efeitos dos fármacos
15.
Nanomedicine (Lond) ; 8(12): 1927-42, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23398497

RESUMO

AIM: Different nanoparticles have been investigated to deliver chemotherapeutic agents, but complex synthesis procedures and biocompatibility issues raise concerns in developing them for safe human usage. The aim of this work is to develop α,ß-dehydrophenylalanine-containing, self-assembled, amphipathic dipeptide nanoparticles for tumor-targeted drug delivery and therapy. MATERIAL & METHODS: Solution-phase peptide synthesis was used to synthesize dipeptides. Nanoparticles were prepared by molecular self-assembly. A tumor distribution study was carried out using a radiolabeling method. Tumor regression studies were carried out in murine ascitic tumors in BALB/c mice and breast tumor xenografts in in nonobese diabetic/severe combined immunodeficiency mice. RESULTS: Arg-α,ß-dehydrophenylalanine formed self-assembled nanoparticles that could be easily derivatized with folic acid. Folic acid-derivatized nanoparticles showed enhanced cellular uptake and, when loaded with doxorubicin, showed enhanced tumor regression compared with underivatized nanoparticles or native drug, without any adverse side effects, both in vitro and in vivo.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Dipeptídeos/química , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Dipeptídeos/metabolismo , Doxorrubicina/farmacocinética , Feminino , Ácido Fólico/química , Ácido Fólico/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Neoplasias/patologia , Fenilalanina/análogos & derivados , Fenilalanina/metabolismo
16.
Int J Nanomedicine ; 7: 4207-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22915849

RESUMO

BACKGROUND: Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility and bioavailability of curcumin, attempts have been made to encapsulate it in liposomes, polymeric nanoparticles (NPs), lipid-based NPs, biodegradable microspheres, cyclodextrin, and hydrogels. METHODS: In this work, we attempted to entrap curcumin in novel self-assembled dipeptide NPs containing a nonprotein amino acid, α, ß-dehydrophenylalanine, and investigated the biological activity of dipeptide-curcumin NPs in cancer models both in vitro and in vivo. RESULTS: Of the several dehydrodipeptides tested, methionine-dehydrophenylalanine was the most suitable one for loading and release of curcumin. Loading of curcumin in the dipeptide NPs increased its solubility, improved cellular availability, enhanced its toxicity towards different cancerous cell lines, and enhanced curcumin's efficacy towards inhibiting tumor growth in Balb/c mice bearing a B6F10 melanoma tumor. CONCLUSION: These novel, highly biocompatible, and easy to construct dipeptide NPs with a capacity to load and release curcumin in a sustained manner significantly improved curcumin's cellular uptake without altering its anticancer or other therapeutic properties. Curcumin-dipeptide NPs also showed improved in vitro and in vivo chemotherapeutic efficacy compared to curcumin alone. Such dipeptide-NPs may also improve the delivery of other potent hydrophobic drug molecules that show poor cellular uptake, bioavailability, and efficacy.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Curcumina/análise , Curcumina/química , Dipeptídeos/administração & dosagem , Dipeptídeos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacocinética , Citometria de Fluxo , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Tamanho da Partícula , Solubilidade , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Ther Deliv ; 2(2): 193-204, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22833945

RESUMO

Synthesis of nanomaterials via 'molecular self-assembly' allows one to define the properties of the nanomaterial by rational design of the individual constituents. Use of peptides for self-assembly offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. Our work focused on the synthesis, characterization and potential biomedical applications of small self-assembled peptide-based nanosystems. We demonstrated that dipeptides containing the conformational restricting residue alpha,beta-dehydrophenylalanine, self-assembled into nanovesicular and nanotubular structures. The nanosystems could encapsulate and release anticancer drugs, showed enhanced stability to proteinase K degradation, a property crucial for them to have a high in vivo half-life, and exhibited no cytotoxicity towards cultured mammalian cells. The dipeptide nanostructures were easily taken up by cells and could evade uptake by reticuloendothelial systems when injected into healthy laboratory animals. Thus, small self-assembling peptides may offer novel scaffolds for the future design of nanostructures with potential applications in the field of drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/administração & dosagem , Peptídeos/administração & dosagem , Animais , Desenho de Fármacos , Luz , Peptídeos/farmacocinética , Conformação Proteica , Espalhamento de Radiação , Distribuição Tecidual
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