ABSTRACT
Introduction
Since decades, cancer is a major public health problem worldwide. The increasing knowledge of molecular and tumor biology has significantly changed the cancer treatment paradigms during the past few years.
Area covered
Conventionally, the first-line treatment of solid tumors is their surgical removal followed by chemotherapy and/or radiation treatment. Unfortunately, these approaches often fail, and the patient may discontinue the treatment before the complete eradication of tumors due to therapeutic and toxicological limitations. In this regard, the nucleic acid-based treatment therapy has been widely used in the management of cancer. However, nucleic acid delivery to the target sites is highly challenging because of their molecular size, difficulties to pass cellular membranes, and susceptibility toward enzymatic and/or chemical degradation.
Expert opinion
Researchers have now overcome many problems associated with delivering nucleic acids to the target tissues by preventing them from off-target side effects and overcoming rapid degradation and clearance in the bloodstream using the lipid–polymer hybrid nanoparticles (LPHNs). The present review, therefore, aims to provide an overview account on LPNHs, their preparation, characterization, application with special emphasis on intracellular delivery/transfection of nucleic acids in the management of cancer, and key aspects of challenges in its delivery and clinical transition.
Article highlights
At worldwide, cancer is a major health problem. It is expected to come 420 million new cancer cases by up to 2025.
Conventional-based formulations for systemic delivery of chemotherapeutic agents have inadequate drug delivery of the drug to the target cell and poor cellular uptake, which results in low quality and expectancy of life.
Lipid–polymer hybrid nanoparticles (LPHNs) emerging as a promising drug delivery system to exploit the drug carrier potential of liposomes and polymeric nanoparticles (NPs) and to overcome their limitations.
LPHNs are biodegradable, stable, and long-lived nanoparticle vector delivery systems.
Two-step and single-step methods are employed for the preparation of LPHNs.
The characterization of LPHNs, done by dynamic light scattering (DLS) and NP tracking analysis (NTA) for size distribution, Zetasizer for surface charge, TEM/SEM for the size-distribution and surface morphology, etc.
Genetic materials are highly unstable due to the possessing of systemic nucleases, poor permeability across the capillary endothelium, presence of anionic charge, the high molecular weight.
Nucleic acid-loaded LPHNs evade reticuloendothelial systems and traverse the cellular barrier, proving endosomal release and nuclear uptake.
The variation in the compositions, manufacturing process of LPHNs, may significantly affect the physiochemical properties and surface functionality also.
At the laboratory scale, the optimizations of various critical attributes such as selection of ingredients, compatibility, homogenization, centrifugation, extrusion, lyophilization, sterilization, etc. are moreover easier, whereas on a large scale, it is difficult to optimize.
The lack of specific regulatory guidelines for the development process and characterization of LPHNs, lacking collaboration among industries and socioeconomic acceptance; these are challenges which restrict their clinical transition.
This box summarizes key points contained in the article.
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.