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Cationic polymers are being developed quickly as gene delivery vectors. For in vivo gene delivery, the cationic polymers are usually further modified by hydrophilic polymer grafting or ligand conjugation, which have been shown to increase the vector stability, gene delivery efficiency and specificity greatly. Some previous research had shown that modified hydrophilic polymer may partly shield the targeting ligand and result in poor delivery specificity. Developing a method to evaluate the influence of PEG modification on targeting delivery is particularly critical to cationic polymer design and gene therapy development. One of most commonly used cationic polymer polylysine (PLL) was chosen as a model. Targeting ligand epidermal growth factor(EGF)was conjugated with PLL to form PLL-EGF. Then hydrophilic polymer polyethylene glycol (PEG) with molecular mass 7 000 and 20 000 were used to modify PLL-EGF respectively to generate PEG7000-g-PLL-EGF and PEG20000-g-PLL-EGF. In BIAcore experiments, epidermal growth factor receptor (EGFR) was conjugated onto BIAcore chip and various PEG modified PLL-EGF solutions were flowed over the chip. By observing the change of RU value, the specific interaction of EGF to EGFR was compared. Compared with PLL-EGF, PEG modified PLL-EGF showed lower association rate and higher disassociation rate to EGFR. Furthermore, compared to PEG7000 modified PLL-EGF, PEG20000 modified PLL-EGF got lower association rate and higher disassociation rate to EGFR. The Scatchard analysis results showed that the interactions between EGFR and PLL-EGF or PEG-PLL-EGF are non-linear. It can be concluded that PEG modification indeed reduced the association rate and enhanced the dissociation rate of EGF to EGFR. The length of PEG chain was also a key factor to influence interaction between ligand and receptor. The results showed that it was critical important to evaluate the influence of PEG modification on delivery specificities. The BIAcore method developed in this paper can successfully evaluate the influence, which would be important for cationic polymer design and its application as potential non-viral gene delivery vectors.

9.China' s process and challenges in achieving the United Nations Millennium Development Goal 5

Xinglin FENG ; Qing YANG ; Ling XU ; Yan WANG ; Yan GUO

Journal of Peking University(Health Sciences) 2011;43(3):391-396

Objective:China was categorized as one of the 68 countdown countries to achieve the United Nations Millennium Development Goals (MDG) 5. This paper aimed to analyze the situation of maternal survival, and coverage of proven cost effective interventions in China, where specific attention was paid to disparities. Methods: National maternal and child mortality surveillance data were used to estimate maternal mortality ratio (MMR). Coverage for proven interventions was analyzed based on National Health Services Survey, where experts' consultations were made for complementation. Results: There had been a significant reduction of MMR in China, however great disparities existed, with rural Ⅱ to Ⅳ areas experiencing 2 to 5 times higher maternal mortality risks than urban areas and accounting for over 70% maternal mortality burdens. Postpartum hemorrhage, pregnancy associated hypertension, embolism and sepsis were the leading causes, and over 75% of the maternal mortality was caused by preventable or curable causes. Maternal health services utilization decreased in accordance with region' s development level. Socioeconomic factors like financial difficulties were the main obstacles hindering access of care.Even those who made deliveries in hospitals faced different probabilities in receiving qualified care according to their socioeconomic standings. Conclusion: China is on track to achieve MDG 5, however great disparities exist. It is necessary to specifically target rural types Ⅱ to Ⅳ areas. Major causes of maternal mortality which can be prevented or averted through the provision of essential obstetrical care. Yet as compared with maternity health needs, insufficient coverage of maternal and child health (MCH) care services and poor service quality are the leading predisposing factors contributing to maternal mortality in China.