Hexosome engineering for targeting of regional lymph nodes

Shen Y. Helvig; Helene Andersen; Maxim Antopolsky; Anu J. Airaksinen; Arto Urtti; Anan Yaghmur; Seyed M. Moghimi

doi:10.1016/j.mtla.2020.100705

Hexosome engineering for targeting of regional lymph nodes

Shen Y. Helvig
, Helene Andersen
, Maxim Antopolsky
, Anu J. Airaksinen
, Arto Urtti
, Anan Yaghmur^*
, Seyed M. Moghimi

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Hexosomes are nanoparticles enveloping inverted discontinuous hexagonal (H_II) liquid crystalline phases that offer exceptional physicochemical characteristics for drug encapsulation and targeted drug delivery. However, the fate of subcutaneously injected hexosomes has rarely been investigated. Here, we have followed the lymphatic fate of a technetium-99 m [^99mTc]-labeled hexosome preparation on subcutaneous injection into the rat footpads with single-photon emission computed tomography (SPECT) in combination with CT. Hexosomes were composed of phytantriol and oleic acid and sterically stabilized with Pluronic F127. High tracer loading efficiency was achieved by chelating [^99mTc]-pertechnetate to 1,12-diamino-3,6,9-triazadodecane-oleic acid conjugates incorporated within the ordered interior nanocompartments of hexosomes. The preparation was characterized by synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy and nanoparticle tracking analysis. On footpad injection, hexosomes rapidly drained into the lymphatic microvessels and distributed not only to the sentinel (popliteal) lymph node, but also to wider lymph nodes (inguinal and iliac nodes) situated along the pathway of the lymph drainage. The observed hexosome drainage kinetics from the injection site and lymphatic distribution pattern is in line with previously established poly(ethylene oxide) configuration attributes of Pluronic F127 in minimizing nanoparticle aggregation at the injection site, and interaction with the ground substance of interstitium, without interfering with macrophage uptake. Accordingly, we discuss the potential utility of Pluronic F127-stabilized hexosomes for lymphatic targeting and future development of simple, yet effective multifunctional lymphotropic agents and theranostics.

Original language	English
Article number	100705
Journal	Materialia
Volume	11
Number of pages	8
DOIs	https://doi.org/10.1016/j.mtla.2020.100705
Publication status	Published - Jun 2020

Funding

Financial support to AY and SMM by the Danish Council for Independent Research | Technology and Production Sciences (references 1335–00150b and DFF- 7017–00,065) is gratefully acknowledged. AY further acknowledges financial support from the Danish Natural Sciences Research Council (DanScatt) for SAXS experiment. The Radiochemistry Services of the Helsinki Animal in Vivo Imaging Platform (HAIP) at the Helsinki Institute of Life Science (HiLIFE) and the Biocenter Finland Real-Time Imaging Platform are acknowledged for their contribution to the radiotracer studies. The authors thank Marjo Vaha, J. Arturo García-Horsman, and Mari Rissanen (Faculty of Pharmacy, Helsinki University), and Sudeep Das (Department of Chemistry, Helsinki University) for dedication and support in animal experiments and SPECT/CT imaging. Prof. Jouko Vepsäläinen and Dr. Janne Weisell from University of Eastern Finland are acknowledged for providing the Spm-Trien chelator for the experiment.

Keywords

Hexosomes
Lymph drainage
Lymph node
SPECT/CT

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@article{7efc985eac044b8fa039d281fd996fbb,

title = "Hexosome engineering for targeting of regional lymph nodes",

abstract = "Hexosomes are nanoparticles enveloping inverted discontinuous hexagonal (HII) liquid crystalline phases that offer exceptional physicochemical characteristics for drug encapsulation and targeted drug delivery. However, the fate of subcutaneously injected hexosomes has rarely been investigated. Here, we have followed the lymphatic fate of a technetium-99 m [99mTc]-labeled hexosome preparation on subcutaneous injection into the rat footpads with single-photon emission computed tomography (SPECT) in combination with CT. Hexosomes were composed of phytantriol and oleic acid and sterically stabilized with Pluronic F127. High tracer loading efficiency was achieved by chelating [99mTc]-pertechnetate to 1,12-diamino-3,6,9-triazadodecane-oleic acid conjugates incorporated within the ordered interior nanocompartments of hexosomes. The preparation was characterized by synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy and nanoparticle tracking analysis. On footpad injection, hexosomes rapidly drained into the lymphatic microvessels and distributed not only to the sentinel (popliteal) lymph node, but also to wider lymph nodes (inguinal and iliac nodes) situated along the pathway of the lymph drainage. The observed hexosome drainage kinetics from the injection site and lymphatic distribution pattern is in line with previously established poly(ethylene oxide) configuration attributes of Pluronic F127 in minimizing nanoparticle aggregation at the injection site, and interaction with the ground substance of interstitium, without interfering with macrophage uptake. Accordingly, we discuss the potential utility of Pluronic F127-stabilized hexosomes for lymphatic targeting and future development of simple, yet effective multifunctional lymphotropic agents and theranostics.",

keywords = "Hexosomes, Lymph drainage, Lymph node, SPECT/CT",

author = "Helvig, \{Shen Y.\} and Helene Andersen and Maxim Antopolsky and Airaksinen, \{Anu J.\} and Arto Urtti and Anan Yaghmur and Moghimi, \{Seyed M.\}",

year = "2020",

month = jun,

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T1 - Hexosome engineering for targeting of regional lymph nodes

AU - Helvig, Shen Y.

AU - Andersen, Helene

AU - Antopolsky, Maxim

AU - Airaksinen, Anu J.

AU - Urtti, Arto

AU - Yaghmur, Anan

AU - Moghimi, Seyed M.

PY - 2020/6

Y1 - 2020/6

N2 - Hexosomes are nanoparticles enveloping inverted discontinuous hexagonal (HII) liquid crystalline phases that offer exceptional physicochemical characteristics for drug encapsulation and targeted drug delivery. However, the fate of subcutaneously injected hexosomes has rarely been investigated. Here, we have followed the lymphatic fate of a technetium-99 m [99mTc]-labeled hexosome preparation on subcutaneous injection into the rat footpads with single-photon emission computed tomography (SPECT) in combination with CT. Hexosomes were composed of phytantriol and oleic acid and sterically stabilized with Pluronic F127. High tracer loading efficiency was achieved by chelating [99mTc]-pertechnetate to 1,12-diamino-3,6,9-triazadodecane-oleic acid conjugates incorporated within the ordered interior nanocompartments of hexosomes. The preparation was characterized by synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy and nanoparticle tracking analysis. On footpad injection, hexosomes rapidly drained into the lymphatic microvessels and distributed not only to the sentinel (popliteal) lymph node, but also to wider lymph nodes (inguinal and iliac nodes) situated along the pathway of the lymph drainage. The observed hexosome drainage kinetics from the injection site and lymphatic distribution pattern is in line with previously established poly(ethylene oxide) configuration attributes of Pluronic F127 in minimizing nanoparticle aggregation at the injection site, and interaction with the ground substance of interstitium, without interfering with macrophage uptake. Accordingly, we discuss the potential utility of Pluronic F127-stabilized hexosomes for lymphatic targeting and future development of simple, yet effective multifunctional lymphotropic agents and theranostics.

AB - Hexosomes are nanoparticles enveloping inverted discontinuous hexagonal (HII) liquid crystalline phases that offer exceptional physicochemical characteristics for drug encapsulation and targeted drug delivery. However, the fate of subcutaneously injected hexosomes has rarely been investigated. Here, we have followed the lymphatic fate of a technetium-99 m [99mTc]-labeled hexosome preparation on subcutaneous injection into the rat footpads with single-photon emission computed tomography (SPECT) in combination with CT. Hexosomes were composed of phytantriol and oleic acid and sterically stabilized with Pluronic F127. High tracer loading efficiency was achieved by chelating [99mTc]-pertechnetate to 1,12-diamino-3,6,9-triazadodecane-oleic acid conjugates incorporated within the ordered interior nanocompartments of hexosomes. The preparation was characterized by synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy and nanoparticle tracking analysis. On footpad injection, hexosomes rapidly drained into the lymphatic microvessels and distributed not only to the sentinel (popliteal) lymph node, but also to wider lymph nodes (inguinal and iliac nodes) situated along the pathway of the lymph drainage. The observed hexosome drainage kinetics from the injection site and lymphatic distribution pattern is in line with previously established poly(ethylene oxide) configuration attributes of Pluronic F127 in minimizing nanoparticle aggregation at the injection site, and interaction with the ground substance of interstitium, without interfering with macrophage uptake. Accordingly, we discuss the potential utility of Pluronic F127-stabilized hexosomes for lymphatic targeting and future development of simple, yet effective multifunctional lymphotropic agents and theranostics.

KW - Hexosomes

KW - Lymph drainage

KW - Lymph node

KW - SPECT/CT

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DO - 10.1016/j.mtla.2020.100705

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