Pharmaceutical Research

, Volume 28, Issue 7, pp 1520–1530

Agarose Surface Coating Influences Intracellular Accumulation and Enhances Payload Stability of a Nano-delivery System

  • Enrica De Rosa
  • Ciro Chiappini
  • Dongmei Fan
  • Xuewu Liu
  • Mauro Ferrari
  • Ennio Tasciotti
Research Paper

DOI: 10.1007/s11095-011-0453-2

Cite this article as:
De Rosa, E., Chiappini, C., Fan, D. et al. Pharm Res (2011) 28: 1520. doi:10.1007/s11095-011-0453-2

ABSTRACT

Purpose

Protein therapeutics often require repeated administrations of drug over a long period of time. Protein instability is a major obstacle to the development of systems for their controlled and sustained release. We describe a surface modification of nanoporous silicon particles (NSP) with an agarose hydrogel matrix that enhances their ability to load and release proteins, influencing intracellular delivery and preserving molecular stability.

Methods

We developed and characterized an agarose surface modification of NSP. Stability of the released protein after enzymatic treatment of loaded particles was evaluated with SDS-page and HPLC analysis. FITC-conjugated BSA was chosen as probe protein and intracellular delivery evaluated by fluorescence microscopy.

Results

We showed that agarose coating does not affect NSP protein release rate, while fewer digestion products were found in the released solution after all the enzymatic treatments. Confocal images show that the hydrogel coating improves intracellular delivery, specifically within the nucleus, without affecting the internalization process.

Conclusions

This modification of porous silicon adds to its tunability, biocompatibility, and biodegradability the ability to preserve protein integrity during delivery without affecting release rates and internalization dynamics. Moreover, it may allow the silicon particles to function as protein carriers that enable control of cell function.

KEY WORDS

agarose hydrogelintracellular deliverynanoporesporous siliconprotein

ABBREVIATIONS

A1

agarose composition 0.125%

A2

agarose composition 0.05%

Ag

agarose coated

APTES

aminopropyltriethoxysilane

BSA

bovine serum albumin

FACS

fluorescence activated cell sorting

FGF

fibroblast growth factor

HPLC

high performance liquid chromatography

HUVEC

human umbilical vein endothelial cells

NC

bare / not coated

NSPs

nanoporous silicon particles

PLGA

poly(lactic-co-glycolic acid)

pSi

porous silicon

SDS-page

sodium dodecyl sulfate polyacrylamide gel electrophoresis

SEM

scanning electron microscope

SiN

silicon nitride

VEGF

vascular endothelial growth factor

Supplementary material

11095_2011_453_MOESM1_ESM.docx (5.5 mb)
ESM 1(DOCX 5663 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Enrica De Rosa
    • 1
  • Ciro Chiappini
    • 2
  • Dongmei Fan
    • 1
  • Xuewu Liu
    • 1
  • Mauro Ferrari
    • 1
  • Ennio Tasciotti
    • 1
  1. 1.The Methodist Hospital Research Institute (TMHRI)HoustonUSA
  2. 2.University of Texas at AustinAustinUSA