Design of nanocarriers for nanoscale drug delivery to enhance cancer treatment using hybrid polymer and lipid building blocks

Abstract

Polymer-lipid hybrid nanoparticles (PLN) are an emerging nanocarrier platform made from building blocks of polymers and lipids. PLN integrate the advantages of biomimetic lipid-based nanoparticles (i.e. solid lipid nanoparticles and liposomes) and biocompatible polymeric nanoparticles. PLN are constructed from diverse polymers and lipids and their numerous combinations, which imparts PLN with great versatility for delivering drugs of various properties to their nanoscale targets. PLN can be classified into two types based on their hybrid nanoscopic structure and assembly methods: Type-I monolithic matrix and Type-II core-shell systems. This article reviews the history of PLN development, types of PLN, lipid and polymer candidates, fabrication methods, and unique properties of PLN. The applications of PLN in delivery of therapeutic or imaging agents alone or in combination for cancer treatment are summarized and illustrated with examples. Important considerations for the rational design of PLN for advanced nanoscale drug delivery are discussed, including selection of excipients, synthesis processes governing formulation parameters, optimization of nanoparticle properties, improvement of particle surface functionality to overcome macroscopic, microscopic and cellular biological barriers. Future directions and potential clinical translation of PLN are also suggested.

Coordinating Biointeraction and Bioreaction of a Nanocarrier Material and an Anticancer Drug to Overcome Membrane Rigidity and Target Mitochondria in Multidrug‐Resistant Cancer Cells

“…Various PLN formulations were prepared by sequential two‐step sonication followed by a self‐assembly process using the formulation compositions presented in Table S1 of the Supporting Information . The particle properties ( Figure a, Figure S3, Supporting Information) indicate that these PLNs are suitable for intravenous (i.v.)…”

“…Prior to making the PLN system, we carefully reviewed properties of unsaturated liquid lipids and identified two candidates of unsaturated fatty acids (FA), i.e., a mono‐unsaturated FA oleic acid (OA) and a poly‐unsaturated fatty acid DHA. Incorporation of low melting temperature FA (i.e., OA or DHA) into PLN could spatially create amorphous form within its solid lipid matrix, thus improving drug loading, colloidal stability and reducing initial burst drug release . Our previous study of mono‐unsaturated OA (unpublished data) showed that PLN made of binary mixtures of OA and a solid lipid improved physicochemical stability and increased encapsulation of a hydrophilic drug (i.e., doxorubicin) via ionic interactions compared to PLN composed only of solid lipids .…”

“…On the other hand, sustained drug release is prefered during systemic circulation of PLN before reaching the tumor site to minimize unnesssary normal tissue toxicity. [5,8a,b] The in vitro drug release assay may not completely reflect what happens in vivo due to the impact of complicated biological systems (e.g., blood protein binding, tumor tissue) on drug release kinetics. However, based on our previous pharmacokinetic studies of PLN[8b] the sustained drug release profile of MMC‐DHA‐PLN should provide sufficient drug within tumor tissue and cancer cells for an anticancer effect.…”

“…Thus, to exploit mitochondrial targets, various mitochondria‐targeted drugs (e.g., prodrugs, mitochondrial peptides) and mitochondriotropics have been investigated. [3c,4] However, MDR cancer cells exhibit multiple barriers to drug uptake, among which overexpression of P‐gp efflux transporters and rigidity of the plasma membrane present the first cellular barrier to drug delivery, preventing mitochondrial drugs from entry into many types of MDR cancer cells. [3c,5,6]…”

Liposomes‐Camouflaged Redox‐Responsive Nanogels to Resolve the Dilemma between Extracellular Stability and Intracellular Drug Release

“…Over the past several decades, nanoparticles are one of the most studied functional materials for cancer therapy with the aim to improve drug solubility, protect the drugs from premature degradation, prolong their blood circulation time, enhance the drug accumulation at the targeted site, and facilitate drug intracellular penetration, thus achieving higher efficiency and lower toxicity . Among various nanocarriers, liposomes are widely considered to be one of the most successful and most promising formulations for efficient anticancer drug delivery, due to their biocompatibility and biodegradability, simplicity in preparation, and flexibility in functionalization .…”