Studies of Drug Delivery and Drug Release of Dendrimer By Dissipative Particle Dynamics
Date Issued
2007
Date
2007
Author(s)
Wu, Yi-Fan
DOI
zh-TW
Abstract
Controlled drug delivery occurs when a polymer, whether natural or synthetic, is judiciously combined with a drug or other active agent in such a way that the active agent is carried and released from the material in a predesigned manner. Using controlled-delivery systems can maintain the drug levels within a desired range, and provide optimal use of the drug in question. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups.
In this work, the behavior of dendrimers in drug carrying and delivery is explored by using Dissipative Particle Dynamics (DPD). The dendrimer is modeled with three generations of inner hydrophobic core (Gcore) and two to three generations of outer hydrophilic shell (Gshell). The total generation (G) of the dendrimer is the sum of Gcore and Gshell. In aqueous solution, the dendrimer can form uni-micelle and can serve as drug carrier. The characteristic times for the drug carrying processes are significantly affected by the Gshell and the repulsive interaction between hydrophilic shell and drug (aphilic-drug). Under the same volume fraction of dendrimer and drug,the characteristic times increases as aphilic-drug increases for dendrimer with fixed Gcore and Gshell. For systems with rather compatible interaction between hydrophilic shell and drug, equilibrium processes proceed at similar speeds irrespective of the dendrimer generation. However,the characteristic times grows as the thickness of the hydrophilic shell (i.e. Gshell) increases for large enough aphilic-drug. Generally speaking, the partition (P = drug concentration within the dendrimer/ drug concentration in the bulk) increases as G increases and P decreases as aphilic-drug increases.
In the study of drug release process, the drug-carried dendrimer is originally placed in the water free of drug. The drug is then released to the bulk phase through diffusion. To simulate the procedure of drug being absorbed by the human body, we remove part of the released drug (30% and 70%) for every 5000 timesteps in our simulation. The results show that the characteristic times remain the same for various aphilic-drug as long as the hydrophilic shells consist of loose structures. For example, Gshell is small enough or the hydrophilic shell is linear instead of dendritic formation. For dendrimers with thick and tight shells, the drug diffuses out much slower as aphilic-drug increases.
Subjects
耗散粒子動力學法
藥物傳遞
dendrimer
DPD
drug delivery
Type
thesis