Doxorubicin-Loaded Silk Fibroin Nanospheres

Abstract

Silk protein from silkworms or spiders is a very promising biomaterial due to its renewability, nontoxicity, biocompatibility and biodegradability, so it has been widely used in biomedical and pharmaceutical fields. In this article, we report our attempt to use regenerated Bombyx mori silkworm silk fibroin (RSF) as a drug-carrier to encapsulate anti-cancer drug doxorubicin (DOX). Firstly, the pristine RSF nanospheres are prepared by using a facile and clean method developed in this laboratory previously based on the self-assembly of silk protein. In brief, after adding a small amount of ethanol into RSF solution, freezing the whole system to -20 ℃ for 24 h, and then defreezing at room temperature. These RSF nanospheres almost have no cytotoxicity because there is no additional organic solvent other than ethanol involved in the preparation process. Afterwards, the DOX-loaded RSF nanospheres with the average sizes ranging from 350 to 400 nm are prepared by simply mixing DOX aqueous solution and RSF nanospheres solution. The characterizations from dynamic light scattering and SEM observation show that DOX-loaded RSF nanospheres have a controllable shape and size, without apparent aggregation. The drug loading is about 4.6%, the encapsulation efficiency is more than 90%, and the release time of such kind of DOX-loaded RSF nanospheres is over 7 days. In addition, these DOX loaded SF-nanospheres show pH-dependent release, that is, the drug releases faster in pH＝5.0 buffer solution than that in pH＝7.4 one. The DOX-loaded in the RSF nanospheres exhibits the similar curative effect to kill or inhibit Hela cells to the free DOX after incubating these drug-loaded nanospheres with Hela cells for 24 or 48 h. All these results, including easy preparation, good biocompatibility, suitable particle size, and considerable anti-cancer efficiency, imply that such kind of biomacromolecule based anti-cancer drug nanocarrier has a great potential for the lymphatic chemotherapy in clinical applications.

Direct Formation of Silk Nanoparticles for Drug Delivery

“…The loading efficiency was comparable or significantly higher than previous silk particle systems. 43,47 The total amount of loaded drug Several studies have confirmed that the DOX loading capacity of silk particles was mainly dependent on negative charge and hydrophobic properties. 5,31 Thus, it is reasonable that the SNPs-F particles had a lower loading percentage at lower ratios.…”

“…Compared to that of SNPs-A, lower drug levels were absorbed on the SNPs-F particles at lower DOX/silk ratios, and then became similar when the ratio was in the range of 0.3–0.6. The loading efficiency was comparable or significantly higher than previous silk particle systems. , The total amount of loaded drug increased and remained constant at about 50 μg after more than 200 μg of DOX was added in aqueous solutions containing 500 μg of silk nanoparticles, suggesting saturation. Several studies have confirmed that the DOX loading capacity of silk particles was mainly dependent on negative charge and hydrophobic properties. , Thus, it is reasonable that the SNPs-F particles had a lower loading percentage at lower ratios.…”

“…Silk nanoparticles have attracted significant attention for anticancer drug delivery, because different anticancer drugs can be loaded effectively and show higher release rate at lower pH conditions. Several strategies including phase separation, salting out, , emulsification, capillary microdot printing, , organic solvent precipitation, , supercritical CO 2 , and freeze-induced self-assembly − have been utilized to form silk nanoparticles with different sizes. The anticancer properties of drug-loaded silk nanoparticles were confirmed with in vitro cell studies. − The colloidal stability of silk nanoparticles was improved through coating with cationic polymers or cross-linking with polyethylene, which facilitated in vivo applications of the drug-loaded silk nanoparticles. , Though several critical improvements have been achieved, further modifications remain necessary because the present preparation processes are relative complex and use organic solvents. , Increasing pH-dependent release behavior for silk nanoparticles would also foster improved targeted therapy.…”

Crystal structure and halogen–hydrogen bonding of a Delépine reaction intermediate

“…Direct comparisons with BUXZEZ (Yang et al, 1983) are difficult because of the disorder around the allyl group while the remaining compounds have other significant intermolecular interactions such as hydrogen bonds formed to bromide by a water molecule (CEXLOG, GINHAN) or from a carboxylic acid (YOYWEO). Similar interactions to compound 1 can be seen where chloride is the halide anion: BIDBIZ (Shao et al, 1982) shows hydrogen bonds from the benzylurotropinium cation to the chloride anion, accounting for 12.2% of the interaction surface.…”

Hydrophilic mesoporous carbon nanospheres with high drug-loading efficiency for doxorubicin delivery and cancer therapy

“…As far as we know, there have been a few nanocarriers that have such high drug-loading efficiency. [19][20][21][22] The oMCNs showed a significant advantage as containers for DOX.…”