Only Perception: 自我組裝的奈米纖維膠可傳遞高濃度藥物

2008-11-03

自我組裝的奈米纖維膠可傳遞高濃度藥物

Self-assembling nano-fiber gel delivers high concentrations of clinically approved drugs
http://www.physorg.com/news143810107.html

October 21, 2008

來自 Harvard-MIT 健康科學與技術部門（HST）與 Brigham and Women's Hospital 的二組科學家已經開發出一種新的、自我組裝的水膠藥物傳遞系統（hydrogel drug delivery system），那具備生物相容性、能有效釋放藥物而且很容易修改。重要的是，這些結構能以高濃度遞送臨床上認可的藥物而不需要藥物載體或產生有毒成份 -- 直到目前為止這都是水凝膠系統的一個問題。

這些發現，可在 Science Direct 找到，而且將發表在 11/25 該期的 Biomaterials 上。

"這種策略能用來開發基於藥物傳遞載體的平台技術，例如，那能夠在回應發炎反應時，依照需求釋出像抗發炎劑這樣的藥物，" Jeffrey Karp, MD 說，HST 生醫工程中心的講師，同時也是這份手稿的副通訊作者。

"將已知、臨床施用的藥物轉換成雙性（amphiphilic）分子，那能經歷自我組裝，是我們目前研究中的關鍵發展；這也許排除了需要使用外部載體來傳遞藥物的需要，" Praveen Kumar Vemula, PhD 說，Brigham and Women's Hospital 的醫學研究者。

"酵素所觸發的凝膠分解已成為我們的關鍵長處，從基於藥物的水膠開發這些傳遞載具的過程中，那扮演一種重要的角色，" 另一位領導研究者 Dr. George John 說，他是 City College of New York 的副教授，另一位研究者目前正在 Albert Einstein College of Medicine of Yeshiva University 工作。

※ 他們以 acetaminophen（普拿疼）以及 antipyretics（退燒藥）開發雙性低分子量的超分子水凝膠（hydrogelators）。

＊ Self-assembled prodrugs: An enzymatically triggered drug-delivery platform
http://dx.doi.org/10.1016/j.biomaterials.2008.09.045

Praveen K. Vemulaa, Gregory A. Cruikshankb, Jeffrey M. Karpa,
and George Johnb
Biomaterials, Article in Press
doi:10.1016/j.biomaterials.2008.09.045

Enzyme catalysis as a tool to disassemble supramolecular hydrogels to control the release of encapsulated drugs provides an opportunity to design a wide range of enzyme-specific low-molecular-weight hydrogelators. In this proof-of-concept work, we report the synthesis of low-molecular-weight amphiphilic prodrugs（前驅藥物）as hydrogelators from a well-known drug acetaminophen (which belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers)). We have shown the ability of prodrugs to self-assemble to form hydrogels that could subsequently encapsulate a second drug such as curcumin, which is a known chemopreventive and anti-inflammatory hydrophobic drug. Upon enzyme-triggered degradation, the hydrogel released single or multiple drugs at physiologically simulated conditions in vitro. Given that the degradation products consist of the drug and a fatty acid, this approach has an advantage over polymer-based prodrugs that generate polymer fragments with heterogeneous chain lengths upon degradation that may present complex toxicity profiles. Additionally, drug-release occurred without burst release. Spectrophotometric experiments supported the drug-release, and the rate was controlled by modulation of temperature and enzyme concentration. Mesenchymal stem cells treated with prodrugs retained their stem cell properties including the capacity of multi-lineage differentiation, and maintained their adhesive and proliferation capacities with high viability. The present biomaterials could have broad applications as drug-delivery vehicles and cell invasive matrices.