Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells

Dede K. W. Man; Luca Casettari; Marco Cespi; Giulia Bonacucina; Giovanni Filippo Palmieri; Stephen C. W. Sze; George P. H. Leung; Jenny K. W. Lam; Philip C. L. Kwok

doi:10.1021/acs.molpharmaceut.5b00085

Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells

Dede K. W. Man, Luca Casettari, Marco Cespi, Giulia Bonacucina, Giovanni Filippo Palmieri, Stephen C. W. Sze, George P. H. Leung, Jenny K. W. Lam^*, Philip C. L. Kwok

^*Corresponding author for this work

Golden Meditech Centre for NeuroRegeneration Sciences

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

41 Citations (Scopus)

Abstract

Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG–PLGA or mPEG–PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200–250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG–PLGA NPs and mPEG–PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery.

Original language	English
Pages (from-to)	2112-2125
Number of pages	14
Journal	Molecular Pharmaceutics
Volume	12
Issue number	6
DOIs	https://doi.org/10.1021/acs.molpharmaceut.5b00085
Publication status	Published - 1 Jun 2015

Scopus Subject Areas

General Medicine

User-Defined Keywords

nanoparticles
PLGA
PLA
cytotoxicity
oleanolic acid
PEGylation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.molpharmaceut.5b00085

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title = "Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells",

abstract = "Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG–PLGA or mPEG–PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200–250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG–PLGA NPs and mPEG–PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery.",

keywords = "nanoparticles, PLGA, PLA, cytotoxicity, oleanolic acid, PEGylation",

author = "Man, {Dede K. W.} and Luca Casettari and Marco Cespi and Giulia Bonacucina and Palmieri, {Giovanni Filippo} and Sze, {Stephen C. W.} and Leung, {George P. H.} and Lam, {Jenny K. W.} and Kwok, {Philip C. L.}",

note = "Funding information: The authors thank PURAC Biochem (The Netherlands) for the generous donation of l-lactide (Purasorb L), d,l-lactide (PURASORB DL), and glycolide (PURASORB G). Professor Henry H. Y. Tong of The School of Health Sciences, Macao Polytechnic Institute, Macao SAR, is thanked for donating the raw oleanolic acid. The authors thank Faculty Core Facility, LKS Faculty of Medicine, The University of Hong Kong, for the assistance of the flow cytometry experiments. Publisher copyright: {\textcopyright} 2015 American Chemical Society",

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doi = "10.1021/acs.molpharmaceut.5b00085",

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T1 - Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells

AU - Man, Dede K. W.

AU - Casettari, Luca

AU - Cespi, Marco

AU - Bonacucina, Giulia

AU - Palmieri, Giovanni Filippo

AU - Sze, Stephen C. W.

AU - Leung, George P. H.

AU - Lam, Jenny K. W.

AU - Kwok, Philip C. L.

N1 - Funding information: The authors thank PURAC Biochem (The Netherlands) for the generous donation of l-lactide (Purasorb L), d,l-lactide (PURASORB DL), and glycolide (PURASORB G). Professor Henry H. Y. Tong of The School of Health Sciences, Macao Polytechnic Institute, Macao SAR, is thanked for donating the raw oleanolic acid. The authors thank Faculty Core Facility, LKS Faculty of Medicine, The University of Hong Kong, for the assistance of the flow cytometry experiments. Publisher copyright: © 2015 American Chemical Society

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG–PLGA or mPEG–PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200–250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG–PLGA NPs and mPEG–PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery.

AB - Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG–PLGA or mPEG–PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200–250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG–PLGA NPs and mPEG–PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery.

KW - nanoparticles

KW - PLGA

KW - PLA

KW - cytotoxicity

KW - oleanolic acid

KW - PEGylation

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JF - Molecular Pharmaceutics

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ER -

Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells

Abstract

Scopus Subject Areas

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UN SDGs

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