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OBJECTIVE: The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. METHODS: The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. RESULTS: SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. CONCLUSIONS: The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.
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Cátions/química , Química Farmacêutica/métodos , Quitosana/química , Mastócitos/química , Nanopartículas/química , Polímeros/química , Animais , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Tamanho da Partícula , Ratos Wistar , Projetos de PesquisaRESUMO
Systemic chemotherapy has been shown to produce side effects. A small fraction of the drug reaches the tumor site; other healthy organs or normal tissues get affected or damaged due to the nonspecific action of these cytotoxic agents. Furthermore, due to their short period of activity, repeat injections are often required, which can lead to the exacerbation of side effects and inconvenience. To overcome these obstacles, in this study, we developed controlled and targeted intratumoral injection. Hydrogel was prepared by physical cross-linking method; however, nanohydrogel was prepared using tip probe-sonicator method. Our results revealed that biodegradable and thermosensitive 5-fluorouracil-loaded methylcellulose nanohydrogel synthesized by physical cross-linking method may be a beneficial approach in targeting the therapeutic agent to the tumor site.
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Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Hidrogéis/síntese química , Temperatura , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fluoruracila/farmacologia , Humanos , Hidrogéis/químicaRESUMO
BACKGROUND: Dengue is an important vector-borne disease with a spectrum of classical fever to hemorrhagic fever to dengue shock syndrome. The present study was conducted with objective to study epidemiological and demographic characteristics of dengue infections during the year 2015 in Saurashtra region, Gujarat state, India. MATERIALS AND METHODS: The study was conducted at Tertiary Care Hospital, Rajkot, during the year 2015. A total of 3312 blood samples were collected and tested for dengue NS1 antigen and IgM antibody by capture ELISA testing from various districts of Saurashtra region. A pretested structured data sheet was used as a tool for data collection, and data analysis was done. RESULTS: Out of 3312 tested samples, 33.4% samples were found positive for dengue. Suspected cases were reported from all age groups, including majority from 15 to 24 years (31.1%) and 25 to 44 years (30.0%) and also 8.4% from 0 to 4 years. More than two-third (68.7%) of males were dengue positive than female cases. Significant numbers of cases (P < 0.01) were residing in urban areas (65.7%). Two-third cases (66.8%) diagnosed after 7 days of fever by IgM antibody test. Increasing number of dengue cases reported from July and reached to peak during October 2015. CONCLUSION: The present study reported that dengue mainly affected males and urban population. Perennial occurrence with seasonal increase during monsoon and postmonsoon months was reported. Effective implementation of vector control measures through efforts toward vector breeding source reduction and with the use of personal prophylactic measures against mosquito bites will help in reducing the dengue prevalence in the community.
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BACKGROUND: The purpose of this study was to investigate Quality by Design (QbD) principle for the preparation of hydrogel products to prove both practicability and utility of executing QbD concept to hydrogel based controlled release systems. Product and process understanding will help in decreasing the variability of critical material and process parameters, which give quality product output and reduce the risk. This study includes the identification of the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) from literature or preliminary studies. METHODS: To identify and control the variability in process and material attributes, two tools of QbD was utilized, Quality Risk Management (QRM) and Experimental Design. Further, it helps to identify the effect of these attributes on CQAs. Potential risk factors were identified from fishbone diagram and screened by risk assessment and optimized by 3-level 2- factor experimental design with center points in triplicate, to analyze the precision of the target process. This optimized formulation was further characterized by gelling time, gelling temperature, rheological parameters, in-vitro biodegradation and in-vitro drug release. RESULTS: Design space was created using experimental design tool that gives the control space and working within this controlled space reduces all the failure modes below the risk level. CONCLUSION: In conclusion, QbD approach with QRM tool provides potent and effectual pyramid to enhance the quality into the hydrogel.
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Portadores de Fármacos , Fluoruracila/administração & dosagem , Hidrogel de Polietilenoglicol-Dimetacrilato , Controle de Qualidade , TemperaturaRESUMO
Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.
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Sistemas de Liberação de Medicamentos , Hidrogéis , Nanoestruturas , Patentes como Assunto , Materiais Biocompatíveis , Pesquisa Biomédica , PolímerosRESUMO
BACKGROUND: The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability. METHOD: The Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3). RESULT: The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of -11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher. CONCLUSION: The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer's patch or paracellular pathway which was proven by confocal microscopy.
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Antifúngicos/farmacocinética , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Itraconazol/farmacocinética , Lipossomos/síntese química , Animais , Antifúngicos/química , Mucosa Intestinal/metabolismo , Intestinos/ultraestrutura , Itraconazol/química , Lipossomos/farmacocinética , Masculino , Nanopartículas , Tamanho da Partícula , Ratos , Ratos Wistar , Propriedades de SuperfícieRESUMO
Hydrogels are cross-linked hydrophilic polymer structures that imbibe large quantities of water or biological fluids. Hydrogels are an upcoming class of polymer-based controlled release drug delivery systems, embracing numerous biomedical and pharmaceutical applications. Hydrogels are swellable polymeric materials, and are being widely investigated as a carrier for drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli responsive changes in their structural network and hence leading to the drug release. The present manuscript is concerned with the classification, method of preparation; application in drug deliveryand FDA approved market products of hydrogels with the patent review on hydrogel composition and its manufacturing process. It also highlights recent advances in hydrogel drug delivery especially stimuli-responsive hydrogel and its patents. This patent review is useful in the synthesis methods of hydrogel drug delivery and its application.