Nanostructured Silica Materials As Drug-Delivery Systems for Doxorubicin: Single Molecule and Cellular Studies

Department of Chemistry and Biochemistry, Center for Nanoscience (CeNS) and Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universitat Munchen, 81377 Munich, Germany.
Nano Letters (Impact Factor: 13.59). 08/2009; 9(8):2877-83. DOI: 10.1021/nl9011112
Source: PubMed


We apply mesoporous thin silica films with nanometer-sized pores as drug carriers and incorporate the widely used anticancer drug Doxorubicin. Through single-molecule based measurements, we gain mechanistic insights into the drug diffusion inside the mesoporous film, which governs the drug-delivery at the target-site. Drug dynamics inside the nanopores is controlled by pore size and surface modification. The release kinetics is determined and live-cell measurements prove the applicability of the system for drug-delivery. This study demonstrates that mesoporous silica nanomaterials can provide solutions for current challenges in nanomedicine.

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Available from: Christoph Bräuchle, Oct 09, 2015
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    • "However, it is highly toxic to the heart and kidneys, thereby limiting its application. Recently, a report of the release of DOX from mesoporous silica films has been described in cellular studies40. Therefore, systems which are able to administer such drug molecules in a controlled and sustained fashion would be very beneficial. "
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    ABSTRACT: The development of nanosized drug delivery systems to transport drugs to target cells, are promising tools to improve the drug therapeutic index. Transport systems should have a simple design to control the release of loaded drug to the target areas, thereby increasing concentration and prolonging retention. Herein, we demonstrate the use of yoctoliter wells (1 yL = 10(-24) L) as simple model systems for the encapsulation and release of biologically active molecules, by manipulating pH. The drug molecule employed here is doxorubicin, which diffuses into the bottom of yoctowells from a bulk solution at pH 7. Capping of the yoctowells is achieved by addition of an anionic-porphyrin by electrostatic interaction. Furthermore, controlled release of the Doxorubcin and capping agent from the yoctowells is achieved by pH control. The effectiveness of the sustain release of the bioactive molecule from yoctowells, provides potential for development of a new generation of drug-delivery system for practical application.
    Scientific Reports 06/2013; 3:1982. DOI:10.1038/srep01982 · 5.58 Impact Factor
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    • "The design of a varied targeted drug delivery system is essential for increasing patient safety and the efficacy of chemotherapy of present anticancer drugs [4] [5]. For this purpose, various investigations have been carried out, and the results have revealed that conjugation [6] or encapsulation [7] of anticancer drugs with polymers [8] may reduce these side effects [7], improve drug distribution in the body, increase their specificity, prolong activity and improve in vivo degradation resistance [9]. Consequently, the encapsulation of drugs into nanoparticles (NPs) has drawn increasing interest. "
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    ABSTRACT: A comparative study is performed on Hypericum perforatum (H. perforatum) and doxorubicin (Dox) anticancer agents. Double emulsion and sonication techniques were used to enhance drug loading efficiency in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). To distinguish the efficiency of the double emulsion method, drug entrapment efficiency was measured. In vitro release studies were carried out to evaluate drug release profiles. Entrapment efficiency was estimated to be 48 and 21% for Dox-loaded and H. perforatum-loaded NPs, respectively. Surprisingly, the encapsulation process disrupted the formation of Dox crystals (Dox in NPs converted from the crystalline to the amorphous phase), whereas disordered crystalline was observed for H. perforatum. In vitro release studies suggested that the total released drug was about 71% of the whole entrapped drug after 20 days. MTT assay confirmed that Dox was more toxic than H. perforatum. This study revealed that H. perforatum is a good choice for further experiments in drug delivery systems because of low cardiotoxicity according to the herbaceous nature of this anticancer agent.
    Micro & Nano Letters 05/2013; 8(5):243-247. DOI:10.1049/mnl.2012.0920 · 0.85 Impact Factor
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    • "On the other hand, most kinds of anticancer agents do not distinguish between cancer cells and the normal ones (5), resulting in adverse reactions in tissue organs (3). Drug delivery systems can reduce these inefficiencies via encapsulation methods, which decrease lesion of the toxic drug, and protect the drug before reaching the target cells (6). Due to lipophilic characteristics of cells membrane, only hydrophobic low molecular weight drugs can cross the membrane (7). "
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    ABSTRACT: Attempts have been made to prepare nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) and doxorubicin. Biological evaluation and physio-chemical characterizations were performed to elucidate the effects of initial drug loading and polymer composition on nanoparticle properties and its antitumor activity. PLGA nanoparticles were formulated by sonication method. Lactide/glycolide ratio and doxorubicin amounts have been tailored. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were employed to identify the presence of doxorubicin within nanospheres. The in vitro release studies were performed to determine the initial ant net release rates over 24 h and 20 days, respectively. Furthermore, cytotoxicity assay was measured to evaluate therapeutic potency of doxorubicin-loaded nanoparticles. Spectroscopy and thermal results showed that doxorubicin was loaded into the particles successfully. It was observed that lactide/glycolide content of PLGA nanoparticles containing doxorubicin has more prominent role in tuning particle characteristics. Doxorubicin release profiles from PLGA 75 nanospheres demonstrated that the cumulative release rate increased slightly and higher initial burst was detected in comparison to PLGA 50 nanoparticles. MTT data revealed doxorubicin induced antitumor activity was enhanced by encapsulation process, and increasing drug loading and glycolide portion. The results led to the conclusion that by controlling the drug loading and the polymer hydrophilicity, we can adjust the drug targeting and blood clearance, which may play a more prominent role for application in chemotherapy.
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