15 Lipid-based nanoparticles for nucleic acids delivery
-
Sonia Sarnelli
Abstract
This chapter highlights challenges and advancements in the production of lipid-based nanoparticles (LNPs) and their application in nucleic acid-based therapies. Recently, mRNA-based vaccines for COVID-19 immunization revealed that the use of nucleic acids is a promising strategy to develop treatments at high therapeutic efficiency and reduced side effects. In this context, LNPs emerged as favourable vehicles for nucleic acids delivery (like mRNA and DNA), due to their biocompatibility, bioavailability, and versatility. The four main components employed to produce LNPs loaded with mRNA are: cationic or ionizable lipids, helper lipids, cholesterol, and PEGylated lipids. Several conventional techniques have been proposed over the years to produce this kind of nanoparticles. However, they show many drawbacks that hinder the direct production of vesicles characterized by a nanometric size, high encapsulation efficiency of the active pharmaceutical ingredient, and prolonged stability. Processes assisted by supercritical fluids (in particular, supercritical CO2) can represent a sustainable and interesting alternative to produce LNPs without using post-processing steps for solvent removal and size reduction that are time-consuming procedures, lead to a large loss of nucleic acids, and negatively influence the general productivity of the process.
Abstract
This chapter highlights challenges and advancements in the production of lipid-based nanoparticles (LNPs) and their application in nucleic acid-based therapies. Recently, mRNA-based vaccines for COVID-19 immunization revealed that the use of nucleic acids is a promising strategy to develop treatments at high therapeutic efficiency and reduced side effects. In this context, LNPs emerged as favourable vehicles for nucleic acids delivery (like mRNA and DNA), due to their biocompatibility, bioavailability, and versatility. The four main components employed to produce LNPs loaded with mRNA are: cationic or ionizable lipids, helper lipids, cholesterol, and PEGylated lipids. Several conventional techniques have been proposed over the years to produce this kind of nanoparticles. However, they show many drawbacks that hinder the direct production of vesicles characterized by a nanometric size, high encapsulation efficiency of the active pharmaceutical ingredient, and prolonged stability. Processes assisted by supercritical fluids (in particular, supercritical CO2) can represent a sustainable and interesting alternative to produce LNPs without using post-processing steps for solvent removal and size reduction that are time-consuming procedures, lead to a large loss of nucleic acids, and negatively influence the general productivity of the process.
Chapters in this book
- Preface V
- List of contributing authors
-
Part I Chemical engineering and medicine
- 1 A systems engineering approach to medicine 3
-
Part II Modelling physiology
- 2 Computational modelling in liver system and liver disease 21
- 3 Inhaled aerosols as carriers of pulmonary medicines and the limitations of in vitro–in vivo correlation (IVIVC) methods 49
- 4 Modelling drug permeation across the skin: a chemical engineering perspective 73
- 5 Chemical engineering contribution to hemodialysis innovation: achieving the wearable artificial kidneys with nanomaterial-based dialysate regeneration 103
-
Part III Disease and treatment
- 6 Precision medicine in hypothyroidism: an engineering approach to individualized levothyroxine dosing 127
- 7 Glucose sensors in medicine: overview 167
- 8 Macroscopic transport models for drugs and vehicles in cancer tissues 185
- 9 Mathematical modelling of hollow-fiber haemodialysis modules 203
- 10 Chemical engineering methods in better understanding of blood hydrodynamics in atherosclerosis disease 243
- 11 On the development of pharmacokinetic models for the characterisation and diagnosis of von Willebrand disease 263
-
Part IV Pharmacokinetics and drug delivery
- 12 An introduction to quantitative systems pharmacology for chemical engineers 293
- 13 A novel strategy for brain cancer treatment through a multiple emulsion system for simultaneous therapeutics delivery 315
- 14 Model-based dose selection for gene therapy for haemophilia B 333
- 15 Lipid-based nanoparticles for nucleic acids delivery 359
- Index
Chapters in this book
- Preface V
- List of contributing authors
-
Part I Chemical engineering and medicine
- 1 A systems engineering approach to medicine 3
-
Part II Modelling physiology
- 2 Computational modelling in liver system and liver disease 21
- 3 Inhaled aerosols as carriers of pulmonary medicines and the limitations of in vitro–in vivo correlation (IVIVC) methods 49
- 4 Modelling drug permeation across the skin: a chemical engineering perspective 73
- 5 Chemical engineering contribution to hemodialysis innovation: achieving the wearable artificial kidneys with nanomaterial-based dialysate regeneration 103
-
Part III Disease and treatment
- 6 Precision medicine in hypothyroidism: an engineering approach to individualized levothyroxine dosing 127
- 7 Glucose sensors in medicine: overview 167
- 8 Macroscopic transport models for drugs and vehicles in cancer tissues 185
- 9 Mathematical modelling of hollow-fiber haemodialysis modules 203
- 10 Chemical engineering methods in better understanding of blood hydrodynamics in atherosclerosis disease 243
- 11 On the development of pharmacokinetic models for the characterisation and diagnosis of von Willebrand disease 263
-
Part IV Pharmacokinetics and drug delivery
- 12 An introduction to quantitative systems pharmacology for chemical engineers 293
- 13 A novel strategy for brain cancer treatment through a multiple emulsion system for simultaneous therapeutics delivery 315
- 14 Model-based dose selection for gene therapy for haemophilia B 333
- 15 Lipid-based nanoparticles for nucleic acids delivery 359
- Index
