Preclinical Evaluation of Genexol-PM, a Nanoparticle Formulation of Paclitaxel, as a Novel Radiosensitizer for the Treatment of Non-Small Cell Lung Cancer

A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease

Formulation of Diblock Polymeric Nanoparticles through Nanoprecipitation Technique

Nanotechnology is a relatively new branch of science that involves harnessing the unique properties of particles that are nanometers in scale (nanoparticles). Nanoparticles can be engineered in a precise fashion where their size, composition and surface chemistry can be carefully controlled. This enables unprecedented freedom to modify some of the fundamental properties of their cargo, such as solubility, diffusivity, biodistribution, release characteristics and immunogenicity. Since their inception, nanoparticles have been utilized in many areas of science and medicine, including drug delivery, imaging, and cell biology1-4. However, it has not been fully utilized outside of "nanotechnology laboratories" due to perceived technical barrier. In this article, we describe a simple method to synthesize a polymer based nanoparticle platform that has a wide range of potential applications

Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity

Nanoparticles’ drug release kinetics can directly affect their therapeutic efficacy and toxicity

Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy

Chemoradiotherapy is a well-established treatment paradigm in oncology. There has been strong interest in identifying strategies to further improve its therapeutic index. An innovative strategy is to utilize nanoparticle (NP)chemotherapeutics in chemoradiation. Since the most commonly utilized chemotherapeutic with radiotherapy is cisplatin, the development of a NP cisplatin for chemoradiotherapy has the highest potential impact on this treatment. Here, we report the development of a NP comprised of polysilsesquioxane (PSQ) polymer crosslinked by a cisplatin prodrug (Cisplatin-PSQ) and its utilization in chemoradiotherapy using non-small cell lung cancer as a disease model. Cisplatin-PSQ NP has an exceptionally high loading of cisplatin. Cisplatin-PSQ NPs were evaluated in chemoradiotherapy in vitro and in vivo. They demonstrated significantly higher therapeutic efficacy when compared to cisplatin. These results suggest that the Cisplatin-PSQ NP holds potential for clinical translation in chemoradiotherapy

Folate-Targeted Polymeric Nanoparticle Formulation of Docetaxel Is an Effective Molecularly Targeted Radiosensitizer with Efficacy Dependent on the Timing of Radiotherapy

Nanoparticle (NP) chemotherapeutics hold great potential as radiosensitizers. Their unique properties, such as preferential accumulation in tumors and their ability to target tumors through molecular targeting ligands, are ideally suited for radiosensitization. We aimed to develop a molecularly targeted nanoparticle formulation of docetaxel (Dtxl) and evaluate its property as a radiosensitizer. Using a biodegradable and biocompatible lipid-polymer NP platform and folate as a molecular targeting ligand, we engineered a folate-targeted nanoparticle (FT-NP) formulation of Dtxl. These NPs have sizes of 72±4 nm and surface charges of −42±8 mV. Using folate receptor over-expressing KB cells and folate receptor low HTB-43 cells, we showed folate-mediated intracellular uptake of NPs. In vitro radiosensitization studies initially showed FT-NP is less effective than Dtxl as a radiosensitizer. However, the radiosensitization efficacy is dependent on the timing of radiotherapy. In vitro radiosensitization conducted with irradiation given at the optimal time (24 hours) showed FT-NP Dtxl is as effective as Dtxl. When FT-NP Dtxl is compared to Dtxl and non-targeted nanoparticle (NT-NP) Dtxl in vivo, FT-NP was found to be significantly more effective than Dtxl or NT-NP Dtxl as a radiosensitizer. We also confirmed that radiosensitization is dependent on timing of irradiation in vivo. In summary, FT-NP Dtxl is an effective radiosensitizer in folate-receptor over-expressing tumor cells. Time of irradiation is critical in achieving maximal efficacy with this nanoparticle platform. To the best of our knowledge, our report is the first to demonstrate the potential of molecularly targeted NPs as a promising new class of radiosensitizers

Estudio del impacto de las nanopartículas de plata sintetizadas con extracto acuoso de Ganoderma applanatum sobre los parámetros tiroideos y lipídicos de la rata albina

Se estudió el impacto de SNP cargadas con extracto de Ganoderma applanatum sobre el perfil tiroideo y lipídico de rata. Las SNP (diámetro medio 58,77 nm; potencial zeta - 3,8) mV se analizaron mediante DLS. La microespectroscopía de infrarrojo con transformada de Fourier proporcionó un pico de transmisión amplio y elevado a 3248,12 cm-1 , que indica la carga bioquímica del extracto de G. applanatum en la superficie de los SNP. No se observó mortalidad ni cambios de comportamiento en la prueba de toxicidad aguda. El grupo-1 recibió 1 mL de agua destilada, el grupo-2 y el grupo-3 recibieron 200 mg kg-1 y 400 mg kg-1 de nanopartículas respectivamente. Una dosis de 400 mg kg-1 de SNPs mostró una mayor actividad hipertiroidea e hipolipidímica en comparación con el control y la dosis de 200 mg kg-1 .Impact of silver nanoparticles loaded with Ganoderma applanatum extract on thyroid and lipid profile of rat were studied. Synthesized SNPs (Average diameter 58.77 nm; -13.8 mV zeta potential) were analysed by dynamic light scattering analysis. Fourier transform infrared spectroscopy provided broad and high transmission peak at 3248.12 cm-1 which indicates the loaded biochemical of the G. applanatum extract on the surface of SNPs. No mortality and behavioural changes were observed in the Acute toxicity test. Group-1 received 1 mL distilled water, group-2 and group-3 received 200 mg kg-1 and 400 mg kg-1 nanoparticles respectively. A 400 mg kg-1 dose of SNPs showed increased hyper thyroid and hypolipidimic activity as compared to control and 200 mg kg-1 dose

Estudio del impacto de nanopartículas de plata sintetizadas mediante extracto acuoso de Ganoderma applanatum sobre parámetros tiroideos y lipídicos de rata albina: Impacto de las nanopartículas de plata en el perfil de lípidos y tiroides

Impact of silver nanoparticles loaded with Ganoderma applanatum extract on thyroid and lipid profile of rat were studied. Synthesized SNPs (Average diameter 58.77 nm; -13.8 mV zeta potential) were analysed by dynamic light scattering analysis. Fourier transform infrared spectroscopy provided broad and high transmission peak at 3248.12 cm-1 which indicates the loaded biochemical of the G. applanatum extract on the surface of SNPs. No mortality and behavioural changes were observed in the Acute toxicity test. Group-1 received 1 mL distilled water, group-2 and group-3 received 200 mg kg-1 and 400 mg kg-1 nanoparticles respectively. A 400 mg kg-1 dose of SNPs showed increased hyper thyroid and hypolipidimic activity as compared to control and 200 mg kg-1 dose.Se estudió el impacto de SNP cargadas con extracto de Ganoderma applanatum sobre el perfil tiroideo y lipídico de rata. Las SNP (diámetro medio 58,77 nm; potencial zeta - 3,8) mV se analizaron mediante DLS. La microespectroscopía de infrarrojo con transformada de Fourier proporcionó un pico de transmisión amplio y elevado a 3248,12 cm-1, que indica la carga bioquímica del extracto de G. applanatum en la superficie de los SNP. No se observó mortalidad ni cambios de comportamiento en la prueba de toxicidad aguda. El grupo-1 recibió 1 mL de agua destilada, el grupo-2 y el grupo-3 recibieron 200 mg kg-1 y 400 mg kg-1 de nanopartículas respectivamente. Una dosis de 400 mg kg-1 de SNPs mostró una mayor actividad hipertiroidea e hipolipidímica en comparación con el control y la dosis de 200 mg kg-1

A Flexible Scalable Hardware Architecture for Radial Basis Function Neural Networks

Radial Basis Function Neural Networks (RBFNN) are used in variety of applications such as pattern recognition, control and time series prediction and nonlinear identification. RBFNN with Gaussian Function as the basis function is considered for classification purpose. Training is done offline using K-means clustering method for center learning and Pseudo inverse for weight adjustments. Offline training is done since the objective function with any fixed set of weights can be computed and we can see whether we make any progress in training. Moreover, minimum of the objective function can be computed to any desired precision, while with online training none of these can be done and it is more difficult and unreliable. In this paper we provide the comparison of RBFNN implementation on FPGAs using soft core processor based multi-processor system versus a network of HyperCells 8], 13]. Next we propose three different partitioning structures (Linear, Tree and Hybrid) for the implementation of RBFNN of large dimensions. Our results show that implementation of RBFNN on a network of HyperCells using Hybrid Structure, has on average 26x clock cycle reduction and 105X improvement in the performance over that of multiprocessor system on FPGAs