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Physicochemical properties and protein interaction of self-assembled gelatin oleic nanoparticles
- Author(s)
- NGUYEN, HONG VAN
- Advisor
- Lee Beom Jin
- Department
- 일반대학원 약학
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-02
- Language
- eng
- Keyword
- gelatin-oleic acid conjugate; aqueous-based self-assemble nanoparticles; physicochemical properties; synthetic optimization; cellular uptake; bovine serum albumin; gelatin-oleic nanoparticles; protein-nanoparticle interaction; precoated bovine serum albumin corona
- Alternative Abstract
- After administration nanoparticle (NP) into biological fluids, NP- protein complex forms and represents “true identity” of NP in our body. The protein corona alters the size and interface composition of a nanomaterial, giving it a new biological identity that is seen by cells. The biological identity determines the physiological response, including agglomeration, cellular uptake, circulation lifetime, kinetics, transport, accumulation, and toxicity. Hence, protein-NP interaction should be carefully investigated to predict and control the fate of NPs including distribution and bioavailability. A numerous studies evaluated the effect of protein on the cellular behavior but mainly using inorganic NPs. In this studied, self-assembled gelatin oleic acid nanoparticles, a polymeric system was used to initial characterization of the effect induce by treatment condition, including media and the presence of protein, mainly BSA. Amphiphilically-modified gelatin contains an inner core that providing a hydrophobic domain to accommodate water-insoluble drugs, whereas the outer gelatin layer accounting for the enhanced biocompatibility and faster biodegradability. Gelatin-oleic acid conjugates (GOC) was synthesized from oleic acid (OA) and gelatin, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) in 60% ethanol. The optimized process for the GOC synthesis was well established. Self-assembled gelatin-oleic acid nanoparticles (GON) were fabricated simply by the desolvation method using dialysis membrane, without adding a cross-linker. GON were formed at a lower critical micelle concentration (CMC) in water, 0.32 mg/mL and homogenous size of 100-300 nm. The GON showed no toxicity in human embryonic kidney cells (HEK 293) and significantly improved coumarin loading in adenocarcinomic human alveolar basal epithelial cells (A549). The current GOC and GON could provide versatile strategies to deliver cargo into the body by acting as a safe and biocompatible nanoparticulate carrier. When administrated, nanoparticles (NPs) will be affected by environment conditions such as pH, composition, temperature and especially proteins. Gelatin-oleic nanoparticles (GON) and bovine serum albumin (BSA), the highest abundance protein in blood were chosen to be evaluated in this study. Influence of BSA at various concentrations on GON stability was characterized by spectroscopy methods. The cellular associations of GON on HEK 293 and A549 cell lines were studied, in two common cell culture media DMEM and RPMI, with and without the addition of BSA at various concentrations. The presence of BSA reduced cellular uptake on both HEK 293 and A549 cell lines in both types of media. However, in the media supplementary with 10% FBS, there was no observation of reduction in cellular uptake, except for media with addition of 10 mg/mL BSA.Preformed corona GON by adsorption of BSA induced lower cellular uptake of GON in A549 cells in RPMI with and without FBS. Therefore, BSA can be used as endogenous ligand applied in NP design to reduce cellular uptake simply by mixing or incubation, but still required thoroughly assessment.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 4. Theses(Ph.D)
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