Ng E Y K, Ng W K
Division of Thermal & Fluids Engineering, School of Mechanical and Aerospace Engineering, College of Engineering, Nanyang Technological University, Nanyang Avenue, Singapore.
J Med Eng Technol. 2007 Jul-Aug;31(4):243-52. doi: 10.1080/03091900500412643.
The aim of this paper is to determine which polymer shape (sphere, hemisphere, cylinder, tablet, cuboid, tetrahedron or octahedron) is best for zero kinetics drug delivery and for sustained nanoparticle release. We applied the Carslaw and Jaeger heat diffusion equations of a sphere with same order of its effective surface area to volume ratio as a reference, to predict how drug delivery would occur in other shapes. The assumption of the heat diffusion analogy in the present study of negligible drug particles is sensible since the drug at nano scale is tiny and thus nearly 'massless'. From tests involving changing the micro-carrier configuration, we can confirm that shape is an important factor to consider when examining drug release rates, to achieve zero-order design. The preliminary analysis suggests that a hemisphere shape is more promising in achieving zero-order drug release rate, followed by a tablet shape of L = 2R(s), 3R(s), a tetrahedron, a cylindrical shape with L = 3R(s), 2R(s), a sphere, a cuboid shape with L = 3R(s), 2R(s), and finally an octahedron. This is due to the larger effective surface area, given the same parameters and surrounding conditions. In other words, a hemisphere shape reaches zero order in the shortest possible time and thus permits sustained zero-order particle release rate. Based on the ratio between the surface area of a micro-carrier and its volume, we further derived the drug release equation of cylinder/tablet shaped micro-carrier. By introducing h as an index of the similarity of the drug release rate to a desirable zero-order drug release rate, we obtained a relationship between different length/radius (L/R) values of cylinder/tablet shapes and the index h. From this relationship, we find the best L/R ratio that can achieve a drug release process most similar to a zero-order drug release process. Future work is to include optimization of the lipid matrixes.
本文的目的是确定哪种聚合物形状(球体、半球体、圆柱体、片剂、长方体、四面体或八面体)最适合零动力学药物递送和纳米颗粒的持续释放。我们应用了具有与其有效表面积与体积比相同阶数的球体的卡尔索夫和耶格尔热扩散方程作为参考,来预测药物在其他形状中如何递送。在本研究中,将药物颗粒视为可忽略不计的热扩散类比假设是合理的,因为纳米级的药物非常微小,因此几乎“无质量”。通过涉及改变微载体构型的测试,我们可以确认形状是检查药物释放速率时要考虑的一个重要因素,以实现零级设计。初步分析表明,半球体形状在实现零级药物释放速率方面更具前景,其次是L = 2R(s)、3R(s)的片剂形状、四面体、L = 3R(s)、2R(s)的圆柱体形状、球体、L = 3R(s)、2R(s)的长方体形状,最后是八面体。这是由于在相同参数和周围条件下,有效表面积更大。换句话说,半球体形状在尽可能短的时间内达到零级,从而允许持续的零级颗粒释放速率。基于微载体的表面积与其体积之间的比率,我们进一步推导了圆柱体/片剂形状微载体的药物释放方程。通过引入h作为药物释放速率与理想零级药物释放速率相似性的指标,我们获得了圆柱体/片剂形状的不同长度/半径(L/R)值与指标h之间的关系。从这种关系中,我们找到了能够实现与零级药物释放过程最相似的药物释放过程的最佳L/R比率。未来的工作是包括脂质基质的优化。