Font Size: a A A

Preparation And Characteristics Of Doxorubicin-Loaded Carboxylic Acid-functionalized Mesoporous Silica Nanoparticles

Posted on:2012-06-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y R GongFull Text:PDF
GTID:2211330338472722Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Doxorubicin (DOX) is one kind of anthracycline antitumor antibiotics. It inhibi-ts the synthesis of RNA and DNA, which can be rapid uptake by body tissue t-hrough intravenous injection. However, besides the treatment, there are serious s-ide effects on heart and other body tissue at the same time, which limited the clinical use of doxorubicin. To this end, through the hydrolysis and condensation of TEOS, we prepared spherical mesoporous silica nanoparticles(MSN), and stud-yed the impact factors on the size of nanoparticles by orthogonal experiment.T-hen we prepared hybrid mesoporous silica nanoparticles (MSN-COOH), which ca-n be used as carriers of anti-cancer drug doxorubicin (DOX). Carrier particles c-an be intaken and released almost completely, and the cytotoxicity of doxorubici-n can be decreased.Carboxy mesoporous silica nanoparticles (MSN-COOH) were prepared using Copolymerization and the shape of nanoparticles was characterized by transmissio-n electron microscopy. The mesoporous structure was confirmed using small ang-le X-ray diffraction and the functional groups was confirmed using infrared spec-tra. Specific surface area (BET) and pore size, pore volume analysis (BJH) was dealt with nitrogen adsorption isotherms. Distribution of nanoparticles by transm-ission electron microscopy showed that the nanoparticles distributed uniformly a-nd the diameter was around 80nm (PDI<0.2). Doxorubicin as a model drug w-as used to prepare the drug nanoparticles containing doxorubicin on the carboxy-1 mesoporous silica nanoparticles for in vitro release study, and we selected diff-erent pH (7.4,6.5 and 5.0) of phosphate buffer salt solution as a release mediu-m to investigate the release characteristics of drug nanoparticles in different pH environment. Experimental results show that the release of doxorubicin was pH sensitive in vitro. The drug nanoparticles had rapid release at lower pH (pH 5.0) and slow release at physiological pH (pH 7.4). Temperature of malignant tissue-s were slightly higher as pH value was lower than the normal one. Both of the-m benefited the drug nanoparticles to reach the tumor tissues, achieving controlle-d release of drugs. This phenomenon is mainly due to the amino group protona-tion at low pH, causing the carboxyl binding capacity decreased, thus promoting the release of doxorubicin. Therefore, the release of doxorubicin was pH sensiti-ve. For the anti-tumor drug delivery system, this kind of characteristics promote drug remained in tumor to release rapidly, reduce the cytotoxicity to normal cel-1s and tissues.We investigated the effect of blank MSN-COOH nanoparticles and MSN-CO-OH-DOX nanoparticles on survival of MCF-7 and Hela cells using MTT. The re-suits showed that the synthesized nanoparticles were basically non-toxie. Cytotox-icity results on MCF-7 and Hela cells showed that doxorubicin encapsulated in the nanoparticles had equivalent effect compared to the free on in vitro, indicatin-g that the particles can be intaken, and released almost completely. Adriamycin nanoparticles had concentration-dependent cytotoxicity and the date showed that t-he cytotoxicity of doxorubicin nanoparticles increased with the concentration incr-easing.As the carrier of passive tumor targeting drug delivery system, the research of nano-based hybrid mesoporous silica nanoparticles have a good prospect and it is worth to be studied deeply.
Keywords/Search Tags:Doxorubicin, hybrid mesoporous silica nanoparticles, release in vitro, toxicity
PDF Full Text Request
Related items