Hausberger A G, Kenley R A, DeLuca P P
Pfizer, Inc., Groton, Connecticut, USA.
Pharm Res. 1995 Jun;12(6):851-6. doi: 10.1023/a:1016256903322.
The objective of the reported work was to quantitatively establish gamma-irradiation dose effects on initial molecular weight distributions and in vitro degradation rates of a candidate erodible biopolymeric delivery system.
Poly(D,L-lactide-coglycolide) (PLGA) porous microparticles were prepared by a phase-separation technique using a 50:50 copolymer with 30,000 nominal molecular weight. The microparticles were subjected to 0, 1.5, 2.5, 3.5, 4.5, and 5.5 Mrad doses of gamma-irradiation and examined by size exclusion chromatography (SEC) to determine molecular weight distributions. The samples were subsequently incubated in vitro at 37 degrees C in pH 7.4 PBS and removed at timed intervals for gravimetric determinations of mass loss and SEC determinations of molecular weight reduction.
Irradiation reduced initial molecular weight distributions as follows (Mn values shown parenthetically for irradiation doses): 0 Mrad (Mn = 25200 Da), 1.5 Mrad (18700 Da), 2.5 Mrad (17800 Da), 3.5 Mrad (13800 Da), 4.5 Mrad (12900 Da), 5.5 Mrad (11300 Da). In vitro degradation showed a lag period prior to zero-order loss of polymer mass. Onset times for mass loss decreased with increasing irradiation dose: 0 Mrad (onset = 3.4 weeks), 1.5 Mrad (2.0 w), 2.5 Mrad (1.5 w), 3.5 Mrad (1.3 w), 4.5 Mrad (1.0 w), 5.5 Mrad (0.8 w). The zero-order mass loss rate was 12%/week, independent of irradiation dose. Onset of erosion corresponded to Mn = 5200 Da, the point where the copolymer becomes appreciably soluble.
The data demonstrated a substantial effect of gamma-irradiation on initial molecular weight distribution and onset of mass loss for PLGA, but no effect on rate of mass loss.
本报告工作的目的是定量确定γ射线辐照剂量对一种候选可蚀性生物聚合物递送系统的初始分子量分布和体外降解速率的影响。
采用相分离技术，使用标称分子量为30,000的50:50共聚物制备聚（D，L-丙交酯-乙交酯）（PLGA）多孔微粒。对微粒进行0、1.5、2.5、3.5、4.5和5.5兆拉德剂量的γ射线辐照，并通过尺寸排阻色谱法（SEC）检测以确定分子量分布。随后将样品在37℃、pH 7.4的磷酸盐缓冲盐溶液（PBS）中进行体外孵育，并在设定的时间间隔取出，通过重量法测定质量损失，通过SEC测定分子量降低情况。
辐照使初始分子量分布降低如下（括号内为辐照剂量对应的数均分子量Mn值）：0兆拉德（Mn = 25200道尔顿），1.5兆拉德（18700道尔顿），2.5兆拉德（17800道尔顿），3.5兆拉德（13800道尔顿），4.5兆拉德（12900道尔顿），5.5兆拉德（11300道尔顿）。体外降解在聚合物质量呈零级损失之前有一个滞后期。质量损失的起始时间随辐照剂量增加而缩短：0兆拉德（起始时间 = 3.4周），1.5兆拉德（2.0周），2.5兆拉德（1.5周），3.5兆拉德（1.3周），4.5兆拉德（1.0周），5.5兆拉德（0.8周）。零级质量损失率为每周12%，与辐照剂量无关。侵蚀的起始对应于Mn = 5200道尔顿，即共聚物变得明显可溶的点。
数据表明γ射线辐照对PLGA的初始分子量分布和质量损失起始有显著影响，但对质量损失速率没有影响。
