Editors: Catarina Melim, Ivana Jarak, Ana Santos, Ana Figueiras

Mixed Polymeric Micelles for Osteosarcoma Therapy: Development and Characterization

eBook: US $59 Special Offer (PDF + Printed Copy): US $108
Printed Copy: US $78
Library License: US $236
ISBN: 978-981-5040-38-8 (Print)
ISBN: 978-981-5040-37-1 (Online)
Year of Publication: 2022
DOI: 10.2174/97898150403711220101

Introduction

Osteosarcoma is a rare bone tumor that has a high incidence among children and young adults. Despite recent therapeutic developments, osteosarcoma still presents major hurdles to achieving successful results, mainly due to the presence of multi-drug-resistant cells.

This monograph primarily aims to provide information about the basic science behind the treatment of osteosarcoma along with experimental results for a novel formulation that overcomes multidrug resistance, and therefore, may serve as a viable treatment option. The book starts with an updated and concise guide to the pathophysiology of the disease, while also introducing the reader to new therapies and materials (specifically chitosan, polyethyleneimine, poloxamers, poloxamines, and Pluronics®) used in the treatment process along with the aims of the experiments present subsequently. Next, the book documents the materials and methods used in developing polymeric micelles for delivering drugs to osteosarcoma sites. By explaining the basics of nanomedicine as a starting point, readers will understand how polymeric micelles act as facilitators of drug transport to cancer cells, and how one can synthesize a small stable micelle (by creating derivatives of base nanomaterials), capable of actively targeting osteosarcoma cells and overcoming multi-drug resistance. The chapter explains the synthesis and characterization techniques of the materials used to develop polymeric micelles.

The results, a reflection of the conjugation of different experimental solutions initiated here, point to a modern route towards the search for a therapeutic solution for osteosarcoma.

The simple, structured presentation coupled with relevant information on the subject of micelle-based nanotherapeutic drug delivery make this monograph an essential handbook for pharmaceutical scientists involved in the field of nanomedicine, drug delivery, cancer therapy and any researchers assisting specialists in clinical oncology for the treatment of osteosarcoma.

Audience: Pharmaceutical scientists and medical oncologists involved in polymeric nanomedicine based drug delivery research and osteosarcoma treatment research.

Preface

Osteosarcoma (OS) is a rare and aggressive bone tumor that impacts mostly children and young adults. In spite of the numerous efforts made to date in the therapeutic field, OS still presents a low patient survival rate, high metastasis and relapse occurrence, mostly due to multidrug-resistant cells. To surpass that, nanomedicine has been extensively investigated for the targeted delivery of genetic material, drugs, or both. Polymeric micelles (PM) are nanosystems that facilitate the targeted transportation of poorly water-soluble drugs to cancer cells. These nanocomposites are composed of amphiphilic block copolymers, such as poloxamers, or Pluronics®, that self-assemble into a micellar structure when in contact with an aqueous solution. Pluronics® F68, and P123 are widely used poloxamers in the pharmaceutical area due to their advantageous characteristics. A micelleplex is formed from the conjugation of amphiphilic copolymer(s), a cationic polymer, linked to genetic material and/or drugs. This is because the cationic property will allow for the transportation of nucleic acids and thus, the possibility for dual therapy. Cationic polymers can be of natural or synthetic origin, such as chitosan or polyethyleneimine (PEI), respectively.

miRNAs have been implicated as participators in the development, metastasis and progression of OS. miRNA-145 is underexpressed in this disease and associated with a worse cancer prognosis. We hypothesize that the delivery of miRNA-145 to OS cells via a micelleplex, composed of Pluronic® F68 and either chitosan or PEI, will be able to inhibit tumor proliferation and migration.

In this work, we aim to elucidate the application of a micelleplex encapsulating miRNA-145 in order to achieve a targeted delivery to OS cells and overcome multidrug resistance, as a new and viable treatment option. As such, we have developed and optimized a mixed PM consisting of Pluronics® P123 and F68 complexed with PEI.

DISCLAIMER

This work was partially published in the following research paper:

Melim, C., Jarak, I., Veiga, F., Figueiras, A. The potential of micelleplexes as a therapeutic strategy for osteosarcoma disease. 3 Biotech 10, 147 (2020). https://doi.org/10.1007/s13205-020-2142-5

FUNDING

This work received financial support from National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência) through project UIDB/50006/2020, co-financed by European Union (FEDER under the Partnership Agreement PT2020). It was also supported by the grant FCT PTDC/BTM-MAT/30255/2017 (POCI-01- 0145-FEDER-030255) from the Portuguese Foundation for Science and Technology (FCT) and the European Community Fund (FEDER) through the COMPETE2020 program.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENT

Declared none.

Ana Figueiras
Department of Pharmaceutical Technology
Faculty of Pharmacy
University of Coimbra
Coimbra, Portugal