Chemistry and Art of Developing Lipid Nanoparticles for Biologics Delivery: Focus on Development and Scale-Up

Abstract

Lipid nanoparticles (LNPs) have gained prominence as primary carriers for delivering a diverse array of therapeutic agents. Biological products have achieved a solid presence in clinical settings, and the anticipation of creating novel variants is increasing. These products predominantly encompass therapeutic proteins, nucleic acids and messenger RNA. The advancement of efficient LNP-based delivery systems for biologics that can overcome their limitations remains a highly favorable formulation strategy. Moreover, given their small size, biocompatibility, and biodegradation, LNPs can proficiently transport therapeutic moiety into the cells without significant toxicity and adverse reactions. This is especially crucial for the existing and upcoming biopharmaceuticals since large molecules as a group present several challenges that can be overcome by LNPs. This review describes the LNP technology for the delivery of biologics and summarizes the developments in the chemistry, manufacturing, and characterization of lipids used in the development of LNPs for biologics. Finally, we present a perspective on the potential opportunities and the current challenges pertaining to LNP technology.

Formulation, development and evaluation of hyaluronic acid-conjugated liposomal nanoparticles loaded with regorafenib and curcumin and their in vitro evaluation on colorectal cancer cell lines

“…The evaporation temperature of 40 °C is selected to ensure gradual evaporation of chloroform below its boiling point (61 °C at standard pressure), preventing lipid degradation and phase transitions. This temperature promotes thin, uniform film formation, facilitating subsequent liposome preparation steps and maintaining lipid stability by staying below their transition temperatures ( John et al, 2024 , Leonenko et al, 2004 , Pan et al, 2012 ).…”

Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies

“…Once a fixed LNP formulation is identified, the requirement to implement commercial-scale production with acceptable cost and rate becomes different and harsher. Scaling up the synthesis of LNPs to GMP level can present challenges, including the high cost of raw materials, overly complex designs, and risks of endotoxin contamination, among others [ 102 ]. Efforts have been input in investigating the stable and sustainable process for LNP-mRNA manufacturing.…”

Effect of Cremophor RH40, Hydroxypropyl Methylcellulose, and Mixing Speed on Physicochemical Properties of Films Containing Nanostructured Lipid Carriers Loaded with Furosemide Using the Box–Behnken Design

“…NLC systems have been extensively studied for various routes of administration, including topical, buccal, ocular, injectable, and even oral drug delivery [ 5 , 7 , 8 , 9 ]. The advantages of NLCs include reduced side-effects, enhanced permeation, and improved bioavailability, and they can be scaled up for industrial production [ 10 , 11 ]. Another advantage is that NLC systems do not require organic solvents in their preparation and can effectively encapsulate hydrophobic drugs [ 12 ].…”