Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles

Azarmi, Shirzad; Tao, Xia; Chen, Hua; Wang, Zhaolin; Finlay, Warren H.; Löbenberg, Raimar; Roa, Wilson

doi:10.1016/j.ijpharm.2006.03.052

Cited by 146 publications

(75 citation statements)

References 22 publications

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“…NP characteristics found in this study were similar to those reported previously (13,(33)(34)(35). The positive zeta potential of gelatin NPs can be explained by using a pH lower than the isoelectrical point of gelatin during NP preparation.…”

Section: Discussionsupporting

confidence: 91%

“…One hundred microliters of isobutyl cyanoacrylate monomer was added dropwise to the dextran solution with continuous stirring at 500 rpm. After 4 h of stirring, the formed NP dispersion was filtered using 0.8 μm nucleopore® membrane filter (Whatman, Ontario, Canada) under vacuum (33). Polysorbate-80-coated PIBCA NPs were prepared by adding 0.1 mg of polysorbate-80 to previously prepared uncoated PIBCA NPs under continuous stirring for 4 h (34).…”

Section: Preparation and Characterization Of Npsmentioning

confidence: 99%

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Microcalorimetric Method to Assess Phagocytosis: Macrophage-Nanoparticle Interactions

AlHallak

Sarfraz

Azarmi

et al. 2010

AAPS J

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Abstract. This study evaluated the use of isothermal microcalorimetry (ITMC) to detect macrophagenanoparticle interactions. Four different nanoparticle (NP) formulations were prepared: uncoated poly (isobutyl cyanoacrylate) (PIBCA), polysorbate-80-coated PIBCA, gelatin, and mannosylated gelatin NPs. Changes in NP formulations were aimed to either enhance or decrease macrophage-NP interactions via phagocytosis. Alveolar macrophages were cultured on glass slabs and inserted in the ITMC instrument. Thermal activities of the macrophages alone and after titration of 100 μL of NP suspensions were compared. The relative interactive coefficients of macrophage-NP interactions were calculated using the heat exchange observed after NP titration. Control experiments were performed using cytochalasin B (Cyto B), a known phagocytosis inhibitor. The results of NP titration showed that the total thermal activity produced by macrophages changed according to the NP formulation. Mannosylated gelatin NPs were associated with the highest heat exchange, 75.4±7.5 J, and thus the highest relative interactive coefficient, 9,269±630 M-1. Polysorbate-80-coated NPs were associated with the lowest heat exchange, 15.2±3.4 J, and the lowest interactive coefficient, 890±120 M-1. Cyto B inhibited macrophage response to NPs, indicating a connection between the thermal activity recorded and NP phagocytosis. These results are in agreement with flow cytometry results. ITMC is a valuable tool to monitor the biological responses to nano-sized dosage forms such as NPs. Since the thermal activity of macrophage-NP interactions differed according to the type of NPs used, ITMC may provide a method to better understand phagocytosis and further the development of colloidal dosage forms.

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Section: Discussionsupporting

confidence: 91%

Section: Preparation and Characterization Of Npsmentioning

confidence: 99%

Microcalorimetric Method to Assess Phagocytosis: Macrophage-Nanoparticle Interactions

AlHallak

Sarfraz

Azarmi

et al. 2010

AAPS J

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“…18 Several chemotherapeutic agents have also been tested for aerosol delivery to patients with lung carcinoma, including cisplatin and doxorubicin. [19][20][21][22] Thus, aerosol delivery cationic lipid-encapsulated DNA is a potentially more efficacious approach for the treatment of lung cancer with gene therapy regimens.…”

Section: Introductionmentioning

confidence: 99%

WT1 gene silencing by aerosol delivery of PEI–RNAi complexes inhibits B16-F10 lung metastases growth

et al. 2009

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The Wilms' tumor gene 1 (WT1) is a universal tumor antigen and consequently a good therapeutic target for the development of gene therapy strategies. Earlier, we reported the in vitro efficacy of WT1 RNAi in the inhibition of B16F10 murine melanoma cell line growth. In this study, we used an aerosol system to deliver WT1 RNAi complexes, polyethyleneimine (PEI)-WT1-1 or PEI-WT1-2, to the lungs of mice with B16F10 lung metastasis. This treatment produced a statistically significant (P ¼ 0.020) reduction in the number and size of lung tumor foci, resulting in decreased lung weight and tumor index in treated mice compared with controls. The WT1 RNAi treatment also reduced the number and size of tumor blood vessels, suggesting decreased angiogenesis. Furthermore, the treated lung tissue showed cells in the tumor infiltrations undergoing apoptosis and elevated expression of the proapoptotic genes Bcl-xS and Bax, suggesting an activation of the intrinsic apoptotic pathway. Overall, WT1-1 treatment prolonged the mean survival time of tumor-bearing mice in comparison with the control and WT1-2-treated mice. Our data show that WT1 gene silencing in vivo by aerosol delivery of PEI-WT1 RNAi complexes is an effective therapeutic strategy for the treatment of lung metastases.

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“…It was hypothesized that this may be partially attributed to uptake of drug by endocytosis, as dose-related cytotoxicity was observed also for blank nanoparticles. This observed formulation effect may be due to the presence of polysorbate 80 in the coating of the particles and would require further evaluation in term of safety for pulmonary administration (Azarmi et al, 2006).…”

Section: Dry Powder Inhalersmentioning

confidence: 99%

Loco-regional administration of nanomedicines for the treatment of lung cancer

et al. 2015

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Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored.

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Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles

Cited by 146 publications

References 22 publications

Microcalorimetric Method to Assess Phagocytosis: Macrophage-Nanoparticle Interactions

Microcalorimetric Method to Assess Phagocytosis: Macrophage-Nanoparticle Interactions

WT1 gene silencing by aerosol delivery of PEI–RNAi complexes inhibits B16-F10 lung metastases growth

Loco-regional administration of nanomedicines for the treatment of lung cancer

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