Lipid Nanoparticles (LNPs) Formulation Service

In recent years, there have been significant advances in the field of drug delivery, with lipid nanoparticles emerging as a promising solution to overcome various challenges faced by traditional drug delivery systems. Here, BOC Sciences, as a leading supplier of lipid nanoparticle products and preparation services tailored for the pharmaceutical industry, has been at the forefront of research and development in this field. We are committed to collaborating with customers in the global life sciences sector to explore the complexity, composition, advantages, formulation, encapsulation of different drugs, and multiple applications of LNPs in modern medicine.

What are Lipid Nanoparticles (LNPs)?

Lipid nanoparticles are spherical vesicles composed of a single (monolayer) or multiple (multilayer) phospholipid bilayers, typically consisting of four components: cationic lipids, helper lipids, cholesterol, and pegylated lipids (PEG-lipids). The earliest lipid nanoparticles utilized cationic lipids, which easily bind with negatively charged nucleic acids. However, these delivery systems based on cationic lipids exhibit toxicity and immunogenicity both in vitro and in vivo. For instance, DOTAP and DOTMA can be neutralized by negatively charged serum proteins, leading to reduced toxicity and efficacy. Pegylated lipids are another crucial component of lipid nanoparticles, with polyethylene glycol lipids (such as DMG-PEG 2000 and DSPE-MPEG-2000) formed by conjugating hydrophilic polyethylene glycol with hydrophobic alkyl chains via phosphate, glycerol, or other linkers. Pegylated lipids reside on the surface of lipid nanoparticles, with lipid domains buried deep within the particles and PEG domains extending from the surface. Cholesterol, possessing hydrophobicity and rigidity, fills the gaps between lipid molecules within the lipid bilayer, promoting vesicle stability. The molecular geometry of cholesterol derivatives further influences the delivery efficacy and biodistribution of lipid nanoparticles. Helper lipids, predominantly phospholipids such as DSPC and DOPE, facilitate cellular uptake and endosomal release by promoting fusion with cell and endosomal membranes.

BOC Sciences' Lipid Nanoparticles Formulation Service

At BOC Sciences, we specialize in the formulation and development of lipid nanoparticles for various drug delivery applications. Our experienced team of researchers and scientists utilize state-of-the-art technology and advanced formulation techniques to design LNPs tailored to the specific requirements of our clients. Whether it's encapsulating hydrophobic drugs, hydrophilic drugs, or nucleic acids, we strive to deliver innovative solutions that meet the highest standards of quality and efficacy.

Our Large-Scale Lipid Nanoparticles Manufacturing Technology

In the field of large-scale Lipid Nanoparticles (LNPs) production, there are two main strategies, namely solvent-based and nonsolvent-based techniques. The solvent-based method involves dissolving lipids in organic solvents and then forming nanoparticles through solvent evaporation or dilution, while the nonsolvent-based technique involves dispersing lipids directly in an aqueous phase. BOC Sciences has been committed to developing LNP production strategies from small to large scale to meet various needs of the pharmaceutical industry, such as size, throughput, etc. Our large-scale LNP production platform primarily focuses on nonsolvent-based techniques, such as High-Pressure Homogenization (HPH) and the microemulsion method.

• High-Pressure Homogenization (HPH) is the cornerstone of nonsolvent-based LNP manufacturing. This mature method dates back to the 1950s and involves dispersing lipid solutions into an aqueous phase and then homogenizing under high pressure. BOC Sciences harnesses the power of HPH to successfully conduct pilot-scale production of both drug-free and drug-loaded LNPs, demonstrating its efficacy in scaling up nanoparticle production.
• The microemulsion method provides another pathway for LNP synthesis. This technique involves preparing stable microemulsions and then controlling the precipitation of LNPs. BOC Sciences addresses the potential drug degradation inherent in this method's heating process by developing advanced mixing equipment and continually optimizing production processes.

BOC Sciences' Lipid Nanoparticles for Drug Delivery

BOC Sciences' LNPs have been successfully used to encapsulate a variety of drug types, including water-insoluble, water-soluble and mRNAs, and the versatile encapsulation platform improves drug stability, bioavailability and targeted delivery.

Water-Insoluble Drugs Delivery

BOC Sciences' LNPs have been used to encapsulate hydrophobic drugs such as docetaxel (DTX), albumin-bound paclitaxel and retinoic acid. There are cases where LNPs have been prepared with lipid materials such as Compritol 888 ATO and Precirol ATO5 and stabilizers such as Pluronic F127 and Span 80. In addition, our LNPs were designed for near-infrared imaging-guided photothermal therapy using IR-780 iodide, and lipid-encapsulated nanoparticles for cisplatin (CDDP) delivery were synthesized.

• DTX -Loaded Solid Lipid Nanoparticles

Solid Lipid Nanoparticles (SLNs) are a novel colloidal carrier consisting of a solid core composed of high melting point lipids encapsulated by safe surfactants. SLNs possess advantages such as preventing drug degradation, increasing physical stability, and maintaining controlled drug release, making them promising for delivering docetaxel (DTX). DTX -loaded SLNs can serve as an excellent drug delivery system to enhance the therapeutic efficacy of anticancer drugs while reducing toxicity and side effects.

• Albumin-Bound Paclitaxel Lipid Nanoparticles

Albumin-bound paclitaxel lipid nanoparticles are a novel solvent-free paclitaxel formulation. The formulation is prepared by high-pressure homogenization of paclitaxel into nanoparticles suspended in colloidal albumin in the presence of serum albumin. The lipid nanoparticles combining albumin and paclitaxel were designed to improve the solubility and stability of paclitaxel and prolong its circulation time in the body. In addition, this system can be used to release the drug near tumor cells through active targeting, reducing the toxic response to normal cells.

Water-Soluble Drugs Delivery

BOC Sciences' LNPs have been used to encapsulate hydrophilic drugs such as Paromomycin and Streptomycin Sulfate (STRS), which can be encapsulated using microemulsions, double emulsions, and other methods. For example, double emulsion has been used to encapsulate insulin for oral administration to overcome the challenges of hydrophilic drug delivery.

Lipid Nanoparticles for RNA Delivery

RNA molecules face challenges in stability, immune clearance, and cellular uptake due to their inherent properties. Strategies to overcome these challenges are necessary for effective therapy delivery. The development of ionizable cationic lipids enables RNA to be efficiently delivered into the cytoplasm. These lipids carry a positive charge under acidic conditions, facilitating interaction with RNA, endosomal escape, and reducing cytotoxicity.

• mRNA LNPs

The effective delivery of mRNA vaccines faces challenges, primarily due to the positive charge and hydrophilicity of nucleic acids hindering their diffusion across cell membranes, as well as degradation caused by endogenous nucleases and uptake by phagocytic cells. To overcome these challenges, efficient delivery systems are needed to effectively transport mRNA at the cellular level. Lipid nanoparticles (LNPs) are one extensively studied and successfully employed carrier for mRNA delivery, offering advantages such as high encapsulation efficiency and efficient cellular transfection.

• siRNA LNPs

The technology based on RNA interference (RNAi) is becoming a versatile tool, widely used in treating various diseases. Small interfering RNA (siRNA) possesses the ability to inhibit the translation of target mRNA, hence regarded as a useful tool in treating diseases like cancer. However, siRNA has drawbacks such as large size and susceptibility to degradation by RNase. To overcome these challenges, lipid nanoparticles (LNPs) are extensively researched and applied, enabling safe and efficient delivery of siRNA to its target sites.

• miRNA LNPs

LNP-miRNA refers to a therapeutic approach utilizing lipid nanoparticles (LNPs) as carriers for effective delivery of microRNA (miRNA). This method aims to overcome various challenges encountered in the in vivo delivery of naked miRNA, such as the negative charge of miRNA, susceptibility to degradation by nucleases in the bloodstream, and off-target effects. By encapsulating miRNA into LNPs, its stability and cellular uptake rate can be improved, thereby enhancing the efficiency of miRNA delivery and therapeutic effects. LNP-miRNA represents a promising therapeutic strategy for overcoming the challenges of miRNA delivery, with broad clinical application prospects, especially in the treatment of major diseases such as cancer and neurodegenerative disorders.

• CRISPR/Cas9 LNPs

LNPs can be designed to deliver CRISPR/Cas9 gene editing components, including guide RNA (gRNA) and Cas9 proteins. These LNPs facilitate precise genome editing by introducing targeted double-strand breaks in DNA to enhance and facilitate the effectiveness of gene therapy.

• Antisense Oligonucleotide (ASO) LNPs

ASO-LNP is a lipid nanoparticle (LNP) loaded with antisense oligonucleotides (ASO), and this therapeutic strategy aims to utilize nanoparticles as carriers to effectively deliver ASOs into target cells for treating various diseases. ASO LNP regulates gene expression by binding to complementary RNA sequences, thereby inhibiting the translation of target mRNA molecules or promoting their degradation. LNP is efficient and safe in delivering ASOs, paving the way for clinical translation.

• RNA Aptamer LNPs

LNPs can be designed as carriers for the delivery of RNA aptamers, which are single-stranded RNA molecules that specifically bind to target molecules, such as proteins or small molecules. RNA aptamers are single-stranded RNA molecules that bind specifically to a target molecule, such as a protein or small molecule.

BOC Sciences' LNPs have been applied in the delivery of RNA for gene editing therapies (such as CRISPR-Cas9 for tumor gene destruction) and mRNA vaccines (such as COVID-19 vaccines) development.

Advantages of BOC Sciences' Lipid Nanoparticles for Drug Delivery

Lipid Nanoparticles (LNPs) offer several advantages over traditional drug delivery systems, making them an attractive option for pharmaceutical applications. These advantages include:

• Higher nucleic acid encapsulation efficiency and effective transfection efficiency
• Increased penetration of tissue to provide treatment
• Protected the potent trigger in LNPs
• Low cytotoxicity and immunogenicity

Applications of BOC Sciences' Lipid Nanoparticles (LNPs)

Lipid Nanoparticles (LNPs) have found diverse applications in modern medicine, ranging from cancer therapy to infectious disease treatment. Some notable applications include:

• Cancer therapy: LNPs enable targeted delivery of chemotherapeutic agents to tumor cells, minimizing systemic toxicity and improving therapeutic outcomes.
• Infectious disease therapy: LNPs have been employed for delivering antimicrobial agents and vaccines, enhancing their efficacy and reducing adverse effects.
• Gene therapy: LNPs serve as efficient carriers for delivering nucleic acid-based therapeutics, such as siRNA and mRNA, for the treatment of genetic disorders and infectious diseases.

Lipid nanoparticles (LNPs) represent a promising platform for drug delivery, offering numerous advantages over conventional drug delivery systems. BOC Sciences is committed to advancing the field of LNPs through innovative research and development, with the goal of delivering safe, effective, and targeted therapeutics to pharmaceutical research and development worldwide.

Case Study

Case Study 1 Advancing RNA Delivery Based on Lipid Nanoparticle Technology with Microfluidic Devices

Figure 1. Schematic diagram of a microfluidic device for lipid nanoparticle-based RNA delivery. (Maeki, M.; et al, 2022)

Microfluidic devices have become a transformative solution for LNP production. These devices offer the benefits of high throughput, precise control of reaction conditions and a continuous production process. In this case, the researchers aimed to optimize LNP production using microfluidic devices. They designed and tested a variety of microfluidic configurations including T-shape, Y-shape, sheath flow, chaotic mixer and asymmetric split recombination mixer. Through careful experimentation and analysis, they determined the most efficient microfluidic setup for consistent and scalable LNP. The adoption of microfluidic devices has revolutionized LNP production for RNA delivery. By precisely controlling mixing kinetics and fluid flow, the researchers obtained uniform LNP with improved stability and encapsulation efficiency.

Case Study 2 Optimizing Lipid Nanoparticle (LNP) Composition for Enhanced Gene Therapy and Vaccine Delivery

Figure 2. A simple schematic of the LNP and its various components. (Albertsen, C. H.; et al, 2022)

This case study examines the contribution of different lipid components of LNP to its overall performance in gene therapy and vaccine delivery. Insights into enhancing LNP formulations for improved therapeutic efficacy were gained by dissecting the role of various lipid components. The case focuses on the impact of lipid composition on key aspects such as size, structure, stability, encapsulation efficiency, cellular uptake and endosomal escape. By analyzing the physicochemical properties of LNP, including the apparent pKa of ionizable lipids, the researchers aimed to elucidate the key factors affecting LNP-mediated gene therapy and vaccine delivery, and further emphasized the importance of lipid composition in modulating LNP function for gene therapy and vaccine delivery.

FAQ

1: What are the applications of lipid nanoparticle delivery systems?

Lipid nanoparticle drug delivery systems are used in a wide variety of areas of drug delivery, including oncology therapy, gene therapy, and immunotherapy. They can improve solubility, stability and biodistribution of drugs, thereby increasing therapeutic efficacy and reducing side effects.

2: What are the advantages of lipid nanoparticle delivery systems over other delivery systems?

Lipid nanoparticles have many advantages over other drug delivery systems, including high biocompatibility, good biodegradability, high drug loading capacity, good targeting, and good drug protection properties.

3: What is lipid nanoparticle drug delivery?

Lipid nanoparticle drug delivery is a technique to encapsulate drug carriers in nanoscale lipid particles for better delivery into specific tissues or cells. These nanoparticles are usually made up of biocompatible lipids and are capable of carrying the drug stably in the body to the target location.

References

1. Maeki, M.; et al. Microfluidic Technologies and Devices for Lipid Nanoparticle-Based RNA Delivery. Journal of Controlled Release. 2022, 344: 80-96.
2. Albertsen, C. H.; et al. The Role of Lipid Components in Lipid Nanoparticles for Vaccines and Gene Therapy. Adv Drug Deliv Rev. 2022, 188: 114416.