An update on strategies for optimizing polymer-lipid hybrid nanoparticle-mediated drug delivery: exploiting transformability and bioactivity of PLN and harnessing intracellular lipid transport mechanism

ABSTRACT

Introduction

Polymer-lipid hybrid nanoparticle (PLN) is an emerging nanoplatform with distinct properties and functionalities from other nanocarrier systems. PLN can be optimized to overcome various levels of drug delivery barriers to achieve desired therapeutic outcomes via rational selection of polymer and lipid combinations based on a thorough understanding of their properties and interactions with therapeutic agents and biological systems.

Areas covered

This review provides an overview of PLN including the motive and history of PLN development, types of PLN, preparation methods, attestations of their versatility, and design strategies to circumvent various barriers for increasing drug delivery accuracy and efficiency. It also highlights recent advances in PLN design including: rationale selection of polymer and lipid components to achieve spatiotemporal drug targeting and multi-targeted cascade drug delivery; utilizing the intracellular lipid transport mechanism for active targeting to desired organelles; and harnessing bioreactive lipids and polymers to magnify therapeutic effects.

Expert opinion

A thorough understanding of properties of PLN components and their biofate is important for enhancing disease site targeting, deep tumor tissue penetration, cellular uptake, and intracellular trafficking of PLN. For futuristic PLN development, active lipid transport and dual functions of lipids and polymers as both nanocarrier material and pharmacological agents can be further explored.

KEYWORDS:

• Polymer lipid hybrid nanoparticles
• transformable size and shape
• multi-targeted nanoparticles
• cascade delivery strategies
• active intracellular transport
• fatty acid binding proteins

Article highlights

• PLN is a versatile and effective nanoplatform capable of loading diverse agents and combinations.

• Rationally selected lipids and polymers enable PLN fabrication with transformable size and shape for enhanced biological performance.

• Fatty acid binding protein-mediated intracellular lipid trafficking pathways facilitate fatty acid-containing PLN transport to intracellular targets, including mitochondria and lipid droplets

• Multi-targeted PLN is able to cross the BBB via receptor-mediated transcytosis, and effectively target disease site by a cascade delivery strategy.

• Bioreactive and bioactive lipids and polymers can be employed to produce anticancer agents intracellularly, or synergistic therapeutic effects with co-loaded agents.

• Design of futuristic PLN to overcome various levels of biological barriers requires a full understanding of the properties of polymer and lipid and their biological interactions.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work is supported in part by the Weston Brain Institute Transformational Grant, University of Toronto Connaught Innovation Award, Killam Research Fellowship by the Canada Council for the Arts, Project Grants from the Canadian Institutes of Health Research, Discovery Grants from the Natural Sciences and Engineering Research Council of Canada, to XY Wu. The authors also acknowledge the University of Toronto Connaught International Scholarship for Doctoral Students and the Pfizer Canada Graduate Fellowship in Pharmaceutical Sciences to T Ahmed.

Notes on contributors

Taksim Ahmed

Dr. Taksim Ahmed received his PhD degree under the supervision of Professor Xiao Yu Wu at the University of Toronto. He obtained B. Pharmacy degree from Jahangirnagar University, Bangladesh in 2009. Afterwards, he worked in ACI Pharmaceuticals LTD, Bangladesh (2009–10). He received his master’s in pharmacy degree from the College of Pharmacy, Chosun University, S. Korea (2012) and second M.Sc. degree at the School of Pharmacy, University of Waterloo, Canada (2015). He is a recipient of Connaught International Scholarship for Doctoral Students and Pfizer Canada Graduate Fellowship in Pharmaceutical Sciences. Currently, he is a Research Fellow at the Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, U.S.A. His current research focuses on the development of nanoparticulate drug delivery systems for the treatment of cancer and infectious disease.

Fuh-Ching Franky Liu

Fuh-Ching (Franky) Liu, R.Ph. is a clinical and research pharmacist that works primarily in a hospital-based practice in the Greater Toronto Area. He received his M.Sc. degree under the supervision of Professor Xiao Yu Wu, and his B.Sc.Phm. at the University of Toronto. His practice has extensively involved the marriage of non-sterile extemporaneous compounding and patient care to assist other health professions in therapeutic decision-making, and to create pharmaceutically-elegant products. His current practice involves provision of direct patient care in acute inpatient and ambulatory settings; accountability and dispensation of drug products for clinical trials; and acting as a pharmacist advisory member of the Research Ethics Board at Halton Healthcare.

Xiao Yu Wu

Dr. Xiao Yu Wu is full professor at the Leslie Dan Faculty of Pharmacy at the University of Toronto, Canada. She received her Ph.D. degree in Chemical Engineering from McMaster University, Canada. After postdoctoral research at the University of Toronto, she joined the Faculty of Pharmacy in 1994. Her research projects are centered on advanced pharmaceutics and drug delivery technologies including blood-brain barrier penetrating nanoparticles for brain cancer and CNS diseases; polymer-lipid hybrid nanoparticles for synergistic drug combination chemotherapy; biocompatible and bioreactive MnO2-containing nanoparticles for enhancing cancer therapies and theranostics of Alzheimer’s disease; computer-aided design of controlled release dosage forms; and glucose-responsive insulin/glucagon delivery.