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Quantitative Structure-Property Relationship for pH-Triggered Drug Release Performance of Acid-Responsive Four/Six-Arms Star Polymeric Micelles

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Abstract

Purpose

The pH-responsive copolymer micelles are widely used as carriers in drug delivery system, but there are few micro-level mechanistically explorations on the pH-triggered drug release. Here we elucidate the relationship between drug release behavior of four/six-arms star copolymer micelles and the copolymer structures.

Method

The net cumulative drug release percentage (En) was taken as the dependent variables, block unit autocorrelation descriptors as independent variables. The quantitative structure-property relationship models of drug release from block copolymers were developed at pH 7.4 and 5.0 of two periods (stage I: 0~12 h, stage II: 12~96 h).

Results

The models built are of good fitting ability, internal predictive ability, stability and statistically significance. Drug diffusion is mainly influenced by the intra-block force, and micellar erosion by inter-block force. At pH 5.0, lowest unoccupied molecular orbital energy of copolymer unit is the main factor influencing the En. Stage I of drug release is affected by hydrophobic property and stage II by regional polar of copolymer molecules.

Conclusion

The models present good performance, factors affecting drug release behavior at different pH conditions can offer guidance for the design of copolymer structures to control the drug release behavior of micelles in a targeted and quantitatively way.

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Abbreviations

δ :

Standardized residual of the sample to be predicted

σ :

Standard residual of the samples

BUA:

Block unit autocorrelation

E n :

Net cumulative drug release percentage during a stage

E r :

Cumulative drug release percentage at time points

F :

Value of F in F-test

f k :

Polymeric molecular characteristic

f ki :

Characteristic value of unit i

h* :

Critical value of leverage h

h i :

Leverage of the ith sample to be predicted

l :

Block unit interval

LUMO:

Lowest unoccupied molecular orbital

m :

Number of samples in the training set

n :

Number of query samples

N :

Unit counts in the summation

p :

Possibility

q :

Total number of descriptors contained in the models

q’ :

Number of descriptors plus one

Q 2 LOO-CV :

Leave-one-out cross-validation correlation coefficient

QSPR:

Quantitative structure-property relationship

R 2 :

Multiple correlation coefficient

R i 2 :

Multiple correlation coefficient in a regression analysis between independent variables xi and other independent variables

R 2 Y-rand, Q 2 Y-rand :

Average values of R2 or Q2LOO-CV in Y-randomization test

s :

Standardized error

x i :

Characteristic matrix of the ith sample to be predicted

X T :

Transpose of matrix X

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Author information

Author notes

  1. Ran Zhang and Li-yang Wen contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510000, People’s Republic of China

    Ran Zhang, Li-yang Wen, Xiao-zhe Yuan & Li-juan Zhang

  2. School of Chemistry and Chemical Engineering, Zhaoqing University, Zhaoqing, 526000, People’s Republic of China

    Wen-sheng Wu

Authors
  1. Ran Zhang
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Correspondence to Li-juan Zhang.

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Zhang, R., Wen, Ly., Wu, Ws. et al. Quantitative Structure-Property Relationship for pH-Triggered Drug Release Performance of Acid-Responsive Four/Six-Arms Star Polymeric Micelles. Pharm Res 36, 20 (2019). https://doi.org/10.1007/s11095-018-2549-4

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