Browsing by Subject "Nanoparticles"
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Item ANTIBODY ENCAPSULATION WITHIN POLYMERIC NANOPARTICLES(2014-03) Gdowski, Andrew; Ranjan, Amalendu; Mukerjee, Anindita; Vishwanatha, JamboorAntibodies represent a large class of drugs that have a number of different therapeutic uses. However, side effects can persist due to off target toxicity that may result when the antibody affects a tissue other than where it is intended to act. The use of targeted nanoparticles is one potential way to deliver an antibody to a specific organ where the antibody can be released in a controlled manner and limit side effects. Purpose (a): The purpose of this study is to characterize a human monoclonal antibody encapsulated within a poly(lactic-co-glycolytic) acid (PLGA) nanoparticle. We hypothesized that encapsulation of an antibody within PLGA nanoparticles is feasible and will release in a favorable manner. Methods (b): AnnexinA2 (AnxA2) IgG antibody was encapsulated within PLGA nanoparticles. Encapsulation efficiency and release kinetics were determined using polyacrylamide gel electrophoresis and coomassie brilliant blue staining. Dynamic light scattering (DLS) from Malvern Zetasizer was used to determine hydrodynamic size and zetapotential. Western blot was accomplished with cell lysates from known AnxA2 expressing cell lines to determine functionality of antibody once released from PLGA nanoparticles. Results (c): Our results show acceptable encapsulation efficiency of AnxA2 within the PLGA nanoparticle. Nanoparticles were formed in a favorable monodisperse manner. Release experiments demonstrate that AnxA2 is released in a controlled manner over a period of 15 days. In addition after release the antibody maintained functionality as evidenced through Western Blot analysis. Conclusions (d): We conclude that encapsulation of IgG monoclonal antibodies is feasible, exhibits sustained release kinetics, and maintains functionality upon release. Further, this encapsulation technique may be used as a method to load antibodies in targeted nanoparticles for release in a tissue specific manner.Item Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles(MDPI, 2023-09-09) Mishra, Ina; Garrett, Meredith; Curry, Stephen; Jameson, Jeffrey; Kastellorizios, MichailLiposomal formulations offer significant advantages as anticancer drug carriers for targeted drug delivery; however, due to their complexity, clinical translation has been challenging. In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil((R)) (doxorubicin hydrochloride liposome injection). Here, interfacial tension (IFT) measurements were investigated as a potential physicochemical characterization tool to aid in liposomal product characterization during development and manufacturing. A pendant drop method using an optical tensiometer was used to measure the interfacial tension of various analogues of Doxil((R)) liposomal suspensions in air and in dodecane. The effect of liposome concentration, formulation (PEG and cholesterol content), presence of encapsulated drug, as well as average particle size was analyzed. It was observed that Doxil((R)) analog liposomes demonstrate surfactant-like behavior with a sigmoidal-shape interfacial tension vs. concentration curve. This behavior was heavily dependent on PEG content, with a complete loss of surfactant-like behavior when PEG was removed from the formulation. In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.Item SR-B1 RHDL DIRECTED NANOPARTICLES AS A DRUG DELIVERY SYSTEM AGAINST TRIPLE NEGATIVE BREAST CANCER(2013-04-12) Johnson, RebeccaPurpose: Triple Negative Breast Cancer (TNBC), is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and < 2% respectively. Current anti-HER2 or hormone positive targeted breast cancer treatments do not benefit TNBC patients; consequently, these patients rely primarily on chemotherapy. Alternative targeted therapies are urgently needed to improve survival for TNBC patients. This study is focused on developing a new approach for filling the current void in effective treatment for TNBC patients. Methods: Cells were seeded and treated with free drug and drug loaded rHDl particle for 24 hours. Cell Viability was determined using the cell viability assay CCK8. 96 well plates were read at 450nm Results: Using the CCK8 cell viability assay preliminary data reveals the potential of Temsirolimus loaded rHDL nanoparticles to reduce the effective concentration at lower doses vs. the free drug in the MDA-MB-231 cell line. Conclusions: rHDL particles are small non-immunogenic nanoparticles that have the potential to decrease the side effects that accompany high concentrations of chemotherapeutic drugs. This study proposes the using the mTOR inhibitor Temsirolimus encapsulated into the rHDL nanoparticle as an effective treatment against TNBC vs the free drug.Item Targeted Delivery of [alpha]-Mangostin to Prostate Cancer Cells Utilizing Reconstituted High-Density Lipoprotein Nanoparticles(2022-08) Kapic, Ammar; Berg, Rance E.; Basha, Riyaz; Ranjan, Amalendu P.Item The Neuroprotective Effects of SA-2-NP in a Mouse Model of RGC Injury(2021-05) Ferguson, Jonathan L.; Stankowska, Dorota L.; Millar, J. Cameron; Tovar-Vidales, TaraDetermine if a novel hybrid compound SA-2 can be delivered to the retina in a nanoparticle formulation and have protective effects on retinal ganglion cells (RGCs) following an optic nerve crush (ONC) model of RGC death. Pattern Electroretinography (PERG) was performed on six- to twelve-week-old female (C57BL/6) mice (n = 1-8 mice per group) prior to performing ONC on the left eye to promote RGC death similar to that seen in normotensive glaucoma. Mice were dosed topically for seven or fourteen days either with SA-2 in polylactic glycolic acid (PLGA) nanoparticles, or empty PLGA nanoparticles. Subsequent PERG was performed at seven day following ONC to reassess RGC function after the optic nerve injury and treatments. The mice were subsequently euthanized and both eyes we enucleated and fixed with paraformaldehyde. The retinas were removed, flat mounts were prepared and immunostained with RBPMS antibody to quantify surviving RGCs. Our study demonstrated that SA-2 can be delivered to the retinal tissue with PLGA nanoparticles. However, following optic nerve crush in mice, at the selected doses and delivery regimen of SA-2, neuroprotective effects determined by RGC counts and PERG analysis were not statistically significant. Following ONC in mice, topically delivered SA-2 loaded nanoparticles demonstrated some trend in neuroprotection without statistical significance. Further investigation is required to delineate the efficacious delivery mode and dose.