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Design of polyanionic nanocarriers based on modified poly (aspartic acid)s for oral administration: synthesis and characterization

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Abstract

This study designed a series of polyanionic nanocarriers based on biodegradable and biocompatible poly (aspartic acid)s for oral administration. First, polysuccinimide (PSI) was synthesized from L-aspartic acid using acid-catalyzed bulk thermal polycondensation and acid-catalyzed thermal polycondensation in a mixture of mesitylene/sulfolane. PSI-C16 was then synthesized by aminolysis with nucleophile, hexadecylamine to react with PSI known as nucleophilic addition. Finally, a series of partially esterified poly (aspartic acid)s was produced by alkaline treatment to afford an amphiphilic polyanion, poly (sodium aspartate-g-hexadecyl aspartate) (Na-PASP-g-C16-PASP). 1HNMR, FTIR, DSC and GPC were utilized to demonstrate and characterize the polymers. The synthesized polyanion could be self-assembled into the nano-scaled micelles and be independent of pH in phosphoric buffer solutions. The hydrodynamic diameter and zeta potential were measured using the dynamic light scattering (DLS) method, and the critical micelle concentration (CMC) was determined using the fluorescence spectrophotometer. The micellar morphologies were examined using transmission electron microscopy (TEM), and atomic force microscopy (AFM) to present the nano-dimensional sphere. The stability of size transition at different pH levels, from strong acid to alkaline, proved that the micelles could stably transport from the stomach to intestinal lumen prior to arriving in the epithelium of the small intestine.

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Acknowledgments

This work was supported by grants from the National Science Council (NSC 99-2221-E-007-007-MY2), Taiwan, Republic of China.

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Authors and Affiliations

  1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, 300, Republic of China

    Shih-Pin Hsu & I-Ming Chu

  2. Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan, Taiwan, 320, Republic of China

    I-Ming Chu

Authors
  1. Shih-Pin Hsu
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Corresponding author

Correspondence to I-Ming Chu.

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Fig. S1

(a) H1NMR (500MHz, DMSO-d6) of 6% hexadecylamine-modified PSI (PSI5k- C166%) in DMSO-d6 (b) H1NMR (500MHz , D2O) of 6% hexadecylamine- modified sodium poly(aspartate) (Na-PASP5k-g-C16-PASP5k6%) in D2O. (DOC 302 kb)

Fig. S2

(a) H1NMR (500MHz, DMSO-d6) of 10% hexadecylamine-modified PSI (PSI5k-C1610%) in DMSO-d6 (b) H1NMR (500MHz , D2O) of 10% hexadecylamine - modified sodium poly(aspartate) (Na-PASP5k-g-C16-PASP5k10%) in D2O. (DOC 295 kb)

Fig. S3

(a) H1NMR (500MHz, DMSO-d6) of 15% hexadecylamine-modified PSI (PSI5k-C1615%) in DMSO-d6 (b) H1NMR (500MHz , D2O) of 15% hexadecylamine -modified sodium poly(aspartate) (Na-PASP5k-g-C16-PASP5k15%) in D2O. (DOC 310 kb)

Fig. S4

(a) H1NMR (500MHz, DMSO-d6) of 6% hexadecylamine-modified PSI (PSI8k-C166%) in DMSO-d6 (b) H1NMR (500MHz , D2O) of 6% hexadecylamine- modified sodium poly(aspartate) (Na-PASP8k-g-C16-PASP8k6%) in D2O. (DOC 238 kb)

Fig. S5

(a) H1NMR (500MHz, DMSO-d6) of 10% hexadecylamine-modified PSI (PSI8k-C1610%) in DMSO-d6 (b) H1NMR (500MHz , D2O) of 10% hexadecylamine -modified sodium poly(aspartate) (Na-PASP8k-g-C16-PASP8k10%) in D2O. (DOC 295 kb)

Fig. S6

(a) H1NMR (500MHz, DMSO-d6) of 15% hexadecylamine-modified PSI (PSI8k-C1615%) in DMSO-d6 (b) H1NMR (500MHz , D2O) of 15% hexadecylamine -modified sodium poly(aspartate) (Na-PASP8k-g-C16-PASP8k15%) in D2O. (DOC 310 kb)

Fig. S7

The GPC/SEC chart of Na-PASP5k-g-C16-PASP5k6% with Mw 5417 (DOC 69 kb)

Fig. S8

The GPC/SEC chart of Na-PASP5k-g-C16-PASP5k10% with Mw 6430 (DOC 76 kb)

Fig. S9

The GPC/SEC chart of Na-PASP5k-g-C16-PASP5k15% with Mw 7370 (DOC 74 kb)

Fig. S10

The GPC/SEC chart of Na-PASP8k-g-C16-PASP8k6% with Mw 8757 (DOC 71 kb)

Fig. S11

The GPC/SEC chart of Na-PASP8k-g-C16-PASP8k10% with Mw 10634 (DOC 77 kb)

Fig. S12

The GPC/SEC chart of Na-PASP8k-g-C16-PASP8k15% with Mw 13681 (DOC 75 kb)

Fig.S13

DSC chart of Na-PASP5k-g-C16-PASP5k6% with Tg 52.86 (DOC 138 kb)

Fig. S14

DSC chart of Na-PASP5k-g-C16-PASP5k10% with Tg 47.84 (DOC 68 kb)

Fig. S15

DSC chart of Na-PASP5k-g-C16-PASP5k15% with Tg 48.72 (DOC 121 kb)

Fig. S16

DSC chart of Na-PASP8k-g-C16-PASP8k6% with Tg 77.02 (DOC 51 kb)

Fig. S17

DSC chart of Na-PASP8k-g-C16-PASP8k10% with Tg 57.19°C (DOC 119 kb)

Fig. S18

DSC chart of Na-PASP8k-g-C16-PASP8k15% with Tg 53.58°C (DOC 117 kb)

Fig. S19

I337.5/I335 ratio of Na-PASP5k-g-C16-PASP5k6% with varying concentration (DOC 52 kb)

Fig. S20

I337.5/I335 ratio of Na-PASP5k-g-C16-PAP5k10% with varying concentration (DOC 52 kb)

Fig. S21

I337.5/I335 ratio of Na-PASP5k-g-C16-PASP5k15% with varying concentration (DOC 50 kb)

Fig. S22

I337.5/I335 ratio of Na-PASP8k-g-C16-PASP8k6% with varying concentration (DOC 54 kb)

Fig. S23

I337.5/I335 ratio of Na-PASP8k-g-C16-PASP8k10% with varying concentration (DOC 51 kb)

Fig. S24

I337.5/I335 ratio of Na-PASP8k-g-C16-PASP8k15% with varying concentration (DOC 51 kb)

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Hsu, SP., Chu, IM. Design of polyanionic nanocarriers based on modified poly (aspartic acid)s for oral administration: synthesis and characterization. J Polym Res 19, 9913 (2012). https://doi.org/10.1007/s10965-012-9913-6

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  • DOI: https://doi.org/10.1007/s10965-012-9913-6

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