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A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.

ABSTRACT: Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects.

SUBMITTER: Sun D

PROVIDER: S-EPMC2956928 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.

Sun Dongmei D Zhuang Xiaoying X Xiang Xiaoyu X Liu Yuelong Y Zhang Shuangyin S Liu Cunren C Barnes Stephen S Grizzle William W Miller Donald D Zhang Huang-Ge HG

Molecular therapy : the journal of the American Society of Gene Therapy 20100622 9

Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumi ...[more]

PMID: 20571541

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Project description:The unique features of Metal-Organic Frameworks (MOFs), including structural flexibility, high surface area, and variable pore size, have drawn attention in cancer therapy. However, despite advances in surface functionalization, engineering structural features, and porosity, achieving controlled release, stability, scalability, and toxicity remains a challenge. The current study reports gold nanoparticle (AuNP) encapsulated dual metal-organic frameworks (MOFs) comprising zeolitic imidazolate (ZIF8) and cobalt-imidazole (ZIF67) by a simple precipitation method for dual drug delivery applications. This combination associates the advantages of AuNPs and MOFs, creating a potent platform for cancer theranostics that combines diagnosis and treatment into one unit. The synthesized composite (AuNPs@ZIF-8/ZIF-67) is functionalized with Folic acid (FA) and loaded with the anticancer agents Curcumin (C) and 5-fluorouracil (5-FU) for co-drug delivery The synthesized composites, namely Au/ZIF8, Au/ZIF8/ZIF67/FA, Au/ZIF8/ZIF67/FA/5-FU, and Au/ZIF8/ZIF67/FA/5-FU/C were characterized using diverse analytical techniques such as FESEM, XRD, FTIR, TEM, and BET. The characterization methods showed that the hybrid MOF structure was stable and intact after AuNP encapsulation and drug loading. The dual MOF composite exhibits a better affinity for loading C and 5-FU with 60% and 40% drug loading capacity, respectively. The simultaneous drug release studies suggest that AuNPs@ZIF-8/ZIF-67 are more responsive to the acidic pH and show a higher cumulative drug release of 5FU and C at the lower value of pH 5. For further validation, the release kinetics data were fitted into the Korsmeyer-Peppas model in the current study. The observed value of n which is less than 0.5 suggests the pseudo-Fickian diffusion mechanism for drug release, demonstrating long-term release of 5FU and C from Au/ZIF8/ZIF67/FA/5-FU/C. The targeted drug delivery system is anticipated to display synergistic therapeutic efficacy from the combined effect of the two anticancer agents and the pH-responsive nature of ZIF systems.

Dataset Information

A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.

Publications

A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.

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