Preparation of Self-assembled Nanodrugs (SANDs) by an Ice-template Assisted Method

Project: Research

View graph of relations


Objectives:Cancer is one of the most fatal diseases and causes millions of human death every year. Much improvement in cancer therapy has been achieved by loading drug molecules into various nanometer-sized carriers. However, the drug loading capacities of such carriers based nanosystems are comparatively low (typically less than 10%). In the meantime, the inert carriers may cause undesirable side effects such as potential systemic toxicity and serious inflammation.Thus, the present proposal aims to:1. Develop efficient and controllable approaches for preparing self-assembled nandrugs (SANDs) without using any inert carrier.2. Develop approach for controlling sizes of the SANDs.3. Demonstrate the preparation of SANDs with multiple drug components.R&D methodology:(1) Design and preparation of self-assembled drug nanoparticles:The project team aims to develop high-preparation-rate and high-controllability approaches for fabricating SANDs with an ice-template assisted approach. Instead of using AAO template as in our previous work, we proposed to use ice as template in this project. A unique property of ice is that its grain boundaries contain relatively mobile molecules, behaving like liquid. We exploit this by using the grain boundaries of ice as the channel for templating SANDs formation. Our preliminary results show that by dropping or injecting drug solutions onto surface of ice cubes, SANDs can be formed inside the ice cubes. The SANDs can be obtained by simply melting the ice.(2) Size control of the SANDs:It is well-known that size of nanomedicine can significantly affect its properties. Thus size control is important. In this project, we propose to control sizes of the SANDs obtained via the ice-template assisted method by controlling microstructures or grain boundary structures of the ice template. For example, we can tune the ratio of nucleation rate vs growth rate of ice crystal by systematically changing the cooling rate, temperature, purity (via dissolving salts into water) and dispersing biodegradable nanoparticles into the ice-forming water (to provide additional heterogeneous nucleation surface). We can also change the SANDs size via tuning temperature and concentration of the drug solution. It is anticipated that the obtained systematic results could provide a more precise picture on the SAND formation mechanisms and allow us to further develop processes with improved efficiency and controllability.(3) Demonstrate the preparation of SANDs with multiple drug components:A single-drug therapeutic treatment remains unsatisfactory for completely curing cancer. So the design and preparation of multicomponent nanodrugs consisting of multiple chemotherapeutic drugs or phototherapeutic agents is highly desired. In this project, we can use either physical doping method or chemical synthesis (post-self-assembly or pre-self-assembly) method to simultaneously load multiple drug components into one SAND particle.Impact and Benefits:Comparing with nanomedicine using inert carriers, SANDs has much higher drug loading capacity (typically < 10 % Vs almost 100 %) and can avoid long-term toxicity and metabolism issues cause by the inert carriers. Currently SANDs are mostly prepared by reprecipitation which has problems of low production rate and poor controllability. It is also difficult to prepare sub-100 nm SANDs using this approach.The PC has reported preparation of SANDs using AAO template with merit of precise size control from 20 -100 nm. However, extraction of the SANDs require dissolving the AAO template with acid or base which is (1) slow and (2) can contaminate/affect sensitive drugs.By using ice as the template, SANDs can be obtained by simply melting the ice. This approach is green and causes minimal contamination to the resulting SANDs. This approach can provide pharmaceutical companies with a green and low cost approach for preparing SANDs, If successful, there will be significant impact to the development of nanomedicine.


Project number9440192
Grant typeITF
Effective start/end date1/06/1830/11/19