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.

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.