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Functional nanovalves on protein-coated nanoparticles for in vitro and in vivo controlled drug delivery.

ABSTRACT: A multifunctional mesoporous drug delivery system that contains fluorescent imaging molecules, targeting proteins, and pH-sensitive nanovalves is developed and tested. Three nanovalve-mesoporous silica nanoparticle (NV-MSN) systems with varied quantities of nanovalves on the surface are synthesized. These systems are characterized and tested to optimize the trade-off between the coverage of nanovalves on the MSNs to effectively trap and deliver cargo, and the remaining underivatized silanol groups that can be used for protein attachments. The NV-MSN system that has satisfactory coverage for high loading and spare silanols is chosen, and transferrin (Tf) is integrated into the system. Abiotic studies are performed to test the operation of the nanovalve in the presence of the protein. In vitro studies are carried out to demonstrate the autonomous activation and function of the nanovalves in the system under biological conditions. Enhanced cellular uptake of the Tf-modified MSNs is seen using fluorescence microscopy and flow cytometry in MiaPaCa-2 cells. The MSNs are then tested using SCID mice, which show that both targeted and untargeted NV-MSN systems are fully functional to effectively deliver cargo. These new multifunctional nanoparticles serve proof of concept of nanovalve functionality in the presence of large proteins and demonstrate another dimension of MSN-based theranostic platforms.

SUBMITTER: Hwang AA

PROVIDER: S-EPMC4327898 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Functional nanovalves on protein-coated nanoparticles for in vitro and in vivo controlled drug delivery.

Hwang Angela A AA Lu Jie J Tamanoi Fuyuhiko F Zink Jeffrey I JI

Small (Weinheim an der Bergstrasse, Germany) 20140905 3

A multifunctional mesoporous drug delivery system that contains fluorescent imaging molecules, targeting proteins, and pH-sensitive nanovalves is developed and tested. Three nanovalve-mesoporous silica nanoparticle (NV-MSN) systems with varied quantities of nanovalves on the surface are synthesized. These systems are characterized and tested to optimize the trade-off between the coverage of nanovalves on the MSNs to effectively trap and deliver cargo, and the remaining underivatized silanol grou ...[more]

PMID: 25196485

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Project description:This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were "minimally irritating" to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.

Dataset Information

Functional nanovalves on protein-coated nanoparticles for in vitro and in vivo controlled drug delivery.

Publications

Functional nanovalves on protein-coated nanoparticles for in vitro and in vivo controlled drug delivery.

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