Computational approach to the design of hyaluronic acid copolymer based doxorubicin micelles

Yujiao Sun,Shirui Mao

Shenyang Pharmaceutical University,Shenyang 110016,China

Computational approach to the design of hyaluronic acid copolymer based doxorubicin micelles

Yujiao Sun*,Shirui Mao*

Shenyang Pharmaceutical University,Shenyang 110016,China

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Compatibility

Doxorubicin

Hyaluronic acid

Micelles

Compatibility between drug and carrier is essential for improving drug loading in particulate drug delivery system.In the last few decades,computational approach for the design of drug delivery system has drawn great attention[1].In this study,solubility parameter was used as a guidance to design a stable micellar system.First of all,using doxorubicin(DOX) as a model drug,the compatibility between DOX and three hyaluronic acid copolymers were predicted using molecular dynamics by calculating the Flory–Huggins interaction parameter(χFH)and mixing energy(Emix)of DOX with three fatty glycerides;glycerol monooleate(GMO),glycerol monolaurate (GML)and glycerol monocaprylin(GMC),and hyaluronic acid (HA)respectively.Rank order was then determined based on the χFHand Emixvalues.Thereafter,HA grafted copolymers were synthesized for experimental study.These copolymers were able to form micelles by self-assembly in aqueous solution.The critical aggregation concentration of three HA copolymers was determined by using 8-Anilino-1-naphthalenesulfonic acid(ANS)as a fuorescent probe,the particle size was measured by dynamic light scattering and morphology of the micelles was characterized by transmission electron microscope.DOX loaded polymeric micelles were prepared by dialysis method for experimental verifcation.Findings obtained from the theoretical predictions agreed well with the experimental results.In conclusion, calculation of χFHand Emix is helpful for guiding the design of a suitable copolymer for preparing drug-loaded micellar systems.

Fig.1–Optimized structure for each copolymer/DOX system(the DOX molecules are red in the picture)(A),Flory–Huggins interaction parameters(χFH)of three copolymers and DOX by molecular dynamics simulation(B).

R E F E R E N C E

[1]Huynh L,Neale C,Pomes R,et al.Computational approaches to the rational design of nanoemulsions,polymeric micelles, and dendrimers for drug delivery.Nanomed Nanotechnol 2012;8:20–36.

*E-mail addresses:yjsharon@163.com(Y.Sun);maoshirui@vip.sina.com(S.Mao).

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.045

1818-0876/©2016 The Authors.Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).