Tazhbayev Yerkeblan, Mukashev Olzhas, Burkeev Meiram, Kreuter Jörg
Chemical Materials Science and Nanochemistry Laboratory, Buketov Karaganda State University, 100026 Karaganda, Kazakhstan.
Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, D-60438 Frankfurt am Main, Germany.
Pharmaceutics. 2019 Aug 12;11(8):410. doi: 10.3390/pharmaceutics11080410.
Human serum albumin nanoparticles (HSA-NPs) have been widely used as drug delivery systems. In most cases, HSA-NPs are formed by the method of desolvation in the presence of glutaraldehyde as a crosslinking agent. In the present study, we showed the possibility of crosslinking human serum albumin (HSA) molecules with natural agents, urea, and cysteine at the nanoparticle level under mild conditions (at room temperature of 20-25 °C). Optimal concentrations of the interacting components (HSA, urea, and cysteine) were found to produce nanoparticles with optimal physico-chemical parameters (particle size, polydispersity, zeta potential, yield, etc.) for application as drug carriers. We used hydroxyurea (HU), a simple organic compound currently used as a cancer chemotherapeutic agent. The results indicated sizes of 196 ± 5 nm and 288 ± 10 nm with a surface charge of -22 ± 3.4 mV and -17.4 ± 0.5 mV for HSA-NPs (20 mg/mL of HSA, 0.01 mg/mL of cysteine, and 10 mg/mL of urea) and HSA-HU-NPs (2 mg/mL of HU), respectively. The yield of the HSA-HU-NPs was ~93% with an encapsulation efficiency of ~77%. Thus, the particles created (immobilized with HU) were stable over time and able to prolong the effect of the drug.
人血清白蛋白纳米颗粒（HSA-NPs）已被广泛用作药物递送系统。在大多数情况下，HSA-NPs是通过在戊二醛作为交联剂存在下的去溶剂化方法形成的。在本研究中，我们展示了在温和条件下（20-25°C室温），在纳米颗粒水平用人血清白蛋白（HSA）分子与天然试剂、尿素和半胱氨酸进行交联的可能性。发现相互作用组分（HSA、尿素和半胱氨酸）的最佳浓度可产生具有最佳物理化学参数（粒径、多分散性、zeta电位、产率等）的纳米颗粒，以用作药物载体。我们使用了羟基脲（HU），一种目前用作癌症化疗药物的简单有机化合物。结果表明，HSA-NPs（20mg/mL的HSA、0.01mg/mL的半胱氨酸和10mg/mL的尿素）和HSA-HU-NPs（2mg/mL的HU）的粒径分别为196±5nm和288±10nm，表面电荷分别为-22±3.4mV和-17.4±0.5mV。HSA-HU-NPs的产率约为93%，包封率约为77%。因此，所制备的颗粒（用HU固定）随时间稳定，并且能够延长药物的作用。
