Numerical simulation of microneedles' insertion into skin

Microneedles have recently received much attention as a novel way for transdermal drug delivery. In this paper, a numerical simulation of the insertion process of the microneedle into human skin is reported using the finite element method. A multilayer skin model consisting of the stratum corneum, dermis and underlying hypodermis has been developed. The effective stress failure criterion has been coupled with the element deletion technique to predict the complete insertion process. The numerical results show a good agreement with the reported experimental data for the deformation and failure of the skin and the insertion force. The influences of the mechanical properties of the skin and the microneedle geometry (e.g. tip area, wall angle and wall thickness) on the insertion force are discussed. The numerical results are helpful for the optimum design of the microneedles for the transdermal drug delivery system.     

Delivery of a lactose derivative of endomorphin 1 to the brain via the olfactory epithelial pathway

The rapid and direct delivery of a neuroactive endomorphin 1 derivative to the brain via nasal delivery is reported. A synthetic derivative of the native opioid peptide, endomorphin 1 bearing a lactose unit on the N-terminus of the peptide has been previously reported to exhibit antinoceceptive activity similar to morphine after both intravenous and oral administration. This compound has been administered nasally to rats and appeared in the olfactory bulb within 10 min of administration with negligible levels appearing in the circulating blood or in the rest of the brain. These results indicate that the peptide is absorbed into the brain via the olfactory epithelial pathway suggesting nasal delivery may be a viable alternative route of delivery in clinical applications.     

刺激响应型脂质体的构建策略及其生物学应用

刺激响应型脂质体作为一种新型纳米载体,已广泛应用于医学、食品及化妆品领域。本文围绕刺激响应型脂质体的制备方式、构建策略及其生物学应用展开了详细的介绍。其中,重点综述了pH敏感型、氧化还原敏感型、酶敏感型、热敏型、光敏型和磁场响应型脂质体的功能原理,并根据给药方式的不同对其应用进行了总结归纳。最后,本文对当前刺激响应型脂质体面临的问题与发展前景作出了概括展望。     

壳聚糖衍生物及其胶束：特性、功能化修饰和在药物传递系统中的应用

壳聚糖是一种天然多糖,具有无毒、可生物降解、生物相容性等诸多优点,但水溶性差的自身特点限制了其在药剂学中的应用,而其经合理的结构设计、修饰和优化,可获得性能良好的两亲性壳聚糖衍生物,这些衍生物在水溶液中能自组装成具有良好药物传输性能（如载药量、稳定性、刺激敏感性、靶向性等）的胶束,并被广泛应用于构建药物传递系统,以改善药物的溶解性、靶向性、生物利用度及耐药性,降低药物的毒副作用。综述壳聚糖衍生物结构对其胶束药物传输性能的影响以及壳聚糖衍生物及其胶束的功能化修饰和在药物传递系统中的应用。     

基于益生菌口服药物递送系统的研究进展

随着当今人们对健康的不断重视,益生菌因其安全、有益于肠道健康的特点逐渐进入人们的视野,并成为食品、医药等领域的热点。然而在口服给药方面,选择使用一种安全、方便、稳定的载体是一个难题。以益生菌为载体的口服给药系统具有优异的安全性和稳定性,同时又可以保护被递送药物通过复杂的体内环境而不受破坏。本文综述了5种常见的基于益生菌的口服药物递送方式：芽孢表面展示、酵母微胶囊、重组益生菌表达、细菌样颗粒和细菌影,并详细介绍了它们各自的结构和优缺点,为口服递送载体的开发奠定了坚实的理论基础。     

Understanding co-loading of doxorubicin and camptothecin on graphene and folic acid-conjugated graphene for targeting drug delivery: classical MD simulation and DFT calculation

Abstract

The surface modification ability is one of the remarkable characters of graphene (G) nanosheet. Based on this strategy, G surface is modified with folic acid (FA) to improve the targeting delivery of chemotherapy agents. The dual delivery strategy for the transport of doxorubicin (DOX) and camptothecin (CPT) by using G and folic acid functionalized G nanocarriers is examined. The density functional theory (DFT) and molecular dynamics (MD) simulation are employed to gain a deep insight into the nature of the drug and the carrier interactions. The obtained results indicate that the drug molecules spontaneously move toward the carriers and form stable complexes. In the graphene-based systems, the drug molecules form strong π-π interactions with the carrier surface. It is found that the FA functionalization of G (FA-G) not only improves targeting effect but also reinforces drug-carrier interaction. Furthermore, the MD and DFT results show that interaction of DOX molecules with G and FA-G is stronger than CPT. We believe that the results obtained from this study can be helpful to improve the drug effectiveness in cancer treatment.

Communicated by Ramaswamy H. Sarma     

Modeling the interaction between anti-cancer drug penicillamine and pristine and functionalized carbon nanotubes for medical applications: density functional theory investigation and a molecular dynamics simulation

Abstract

The present study focuses on the prediction and investigation of binding properties of penicillamine with pure (5,5) single-walled carbon nanotube (SWCNT) and functionalized SWCNT (f-SWCNT) through the B3LYP and M06-2X functionals using the 6-31G** basis set. The electronic and structural properties, adsorption energy and frontier molecular orbitals of various configurations are examined. Our theoretical results indicated that the interaction of the nanotubes with penicillamine molecule is weak so that the drug adsorption process is typically physisorption. Also, results of theoretical calculations show that the adsorption of the drug molecule on f-SWCNT is stronger with shorter intermolecular distances in comparison to pure SWCNT. The natural bond orbital (NBO) analysis of studied systems demonstrates that the charge is transferred from penicillamine molecule to the nanotubes. Furthermore, molecular dynamics (MD) simulation is employed to evaluate the dynamic and diffusion behavior of drug molecule on SWCNT and f-SWCNT. Energy results show that drug molecule spontaneously moves toward the carriers, and the van der Waals energy contributions in drug adsorption are more than electrostatic interaction. The obtained results from MD simulation confirm that the functionalization of SWCNT leads to increase in the solubility of the carrier in aqueous solution.

Communicated by Ramaswamy H. Sarma     

血脑屏障与脑药物转运

血脑屏障的存在使大分子药物难以进入脑中发挥疗效。成为中枢神经系统疾病治疗的瓶颈。本就血脑屏障的结构特点、大分子药物转运入脑的途径及药物与载体间的连接策略等问题进行了综述。     

Targeted drug delivery in pancreatic cancer

Effective drug delivery in pancreatic cancer treatment remains a major challenge. Because of the high resistance to chemo and radiation therapy, the overall survival rate for pancreatic cancer is extremely low. Recent advances in drug delivery systems hold great promise for improving cancer therapy. Using liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule inhibitor, and antibody has been a success in recent preclinical trials. However, how to improve the specificity and stability of the delivered drug using ligand or antibody directed delivery represent a major problem. Therefore, developing novel, specific, tumor-targeted drug delivery systems is urgently needed for this terrible disease. This review summarizes the current progress on targeted drug delivery in pancreatic cancer and provides important information on potential therapeutic targets for pancreatic cancer treatment.     

多肽介导的核酸药物递送系统研究进展

核酸药物作为新型基因治疗药物备受关注,但生物学稳定性差、易被体内核酸酶降解、生物利用度低、靶组织内聚集浓度低等是制约其发展的主要因素。新的药物递送技术的快速发展在一定程度上解决了核酸药物的稳定性及靶向递送问题,极大地推动了核酸药物的研发进展。尤其是多肽蛋白类递送载体,已成为核酸药物递送系统研究领域的热点之一。介绍核酸药物递送载体多肽修饰的两种主要方式——共价缀合和非共价络合,重点综述近年来多肽缀合物和复合物以及多肽修饰的载体在核酸药物递送系统中的应用研究,探讨多肽介导的核酸药物递送系统在应用中存在的问题,为新型核酸药物递送系统研发提供参考。     

量子点在新药开发中的应用

由于具有优异的光学特性,量子点在生物医学领域内的研究和应用取得了一些有意义的进展,同时也引起了新药开发人员的兴趣.本文概述了量子点在新药开发中所具有的优势,分析了量子点在药物传输、药物筛选和药靶确证方面的潜在应用,进一步讨论了当前量子点应用于新药开发存在的问题和不足.