Branched Lipid

Branched-chain lipids are a unique class of lipids that play a crucial role in various biological processes. These lipids contain branching points in their hydrocarbon chains, which distinguish them from more common linear lipids. Branched-chain lipids exist in the cell membrane, which contributes to the fluidity, stability and function of the membrane. In addition, branched lipids are characterized by their branched alkyl chains, which have obvious advantages over traditional lipids, making them a promising candidate for enhancing drug delivery systems.

BOC Sciences is a leading supplier of high-quality lipids for research and development purposes. With a strong commitment to innovation and customer satisfaction, BOC Sciences offers a broad range of branched-chain lipid products designed to meet the diverse needs of researchers and scientists across industries. We are committed to providing a diverse portfolio of branched-chain lipids, including phospholipids, glycolipids, and sphingolipids. This broad product range enables researchers to select the branched-chain lipids that best suit their research needs, whether they are studying drug development, drug delivery or genetic engineering. BOC Sciences' branched lipid products are available in a variety of quantities and formulations to meet different study sizes and requirements. In addition to its product diversity, BOC Sciences offers custom lipid synthesis services for researchers who require specialized branched-chain lipid products for their research projects. If you are interested in our lipid products, please contact us for more information.

What are Branched Lipids?

Branched lipids are characterized by the presence of one or more branching points in their hydrocarbon chains. These branching points can appear at different positions on the chain to form various branched lipid structures. The most common type of branched lipids is isoprenoid lipids, which contain isoprenoid units as branching points. Isoprene is a five-carbon structural unit that can be connected together to form a complex branch structure. Another important type of branched lipid is acetal phospholipid, which contains a vinyl ether bond at the sn-1 position of the glycerol backbone. This unique bond introduces kinks into the lipid chain, thereby increasing the fluidity and flexibility of the membrane. Acetal phospholipids are abundant in brain and heart tissues and play an important role in cell signal transduction and membrane integrity.

Branched Lipids in Drug Delivery

Multifunctional branched-chain lipids can be used in various drug delivery systems, such as lipid nanoparticles, micelles, liposomes, etc. By incorporating branched lipids into these delivery systems, it is possible to regulate drug release kinetics, enhance drug stability and improve cell uptake. In addition, branched liposome-encapsulated drug carriers can achieve sustained drug delivery by prolonging the drug delivery time.

Enhancing drug stability

Branched lipids have been shown to enhance the stability of encapsulated drugs by providing an environment that protects active pharmaceutical ingredients from degradation or premature release. This property is particularly valuable for sensitive drugs that are easily degraded under physiological conditions.

Improving the efficiency of drug delivery

Effective drug delivery depends on the ability of the carrier to transport the therapeutic agent to the target site in a controlled manner. Branched lipids can affect the drug release kinetics of lipid-based carriers, thereby achieving a sustained and controlled drug release curve. This controlled release mechanism not only improves the bioavailability of the drug, but also reduces the frequency of administration and improves patient compliance and therapeutic effect.

Targeted drug delivery

Targeted drug delivery is a key strategy for precision medicine, which aims to specifically deliver drugs to diseased tissues while minimizing contact with healthy cells. Branched-chain lipids can be functionalized with targeted ligands or antibodies to promote specific interactions with cell surface receptors or biomarkers associated with disease status. This targeted method enhances the accumulation of drugs at the site of action, maximizes the therapeutic effect and minimizes systemic toxicity.

Case Study

Case Study 1

Problems such as insufficient drug loading and insufficient control of drug leakage severely limit the duration of action of liposomes as drug carriers and can cause potential toxicity. In view of this, Daniel et al. constructed a new liposome system whose design was inspired by the low permeability of archaeal membranes to protons and solutes.

Fig. 1. Methyl-branched liposomes as a depot for sustained drug delivery (Nano Lett. 2023, 23(20): 9250-9256).

(1) The experiment incorporated methyl branched-chain phospholipids into the lipid bilayer to reduce drug diffusion on the liposome membrane, thereby increasing the drug loading capacity by 10%-16% and reducing the drug loading capacity within the first 24 hours. Molecular release is reduced by 40%-48%. The researchers then demonstrated the in vivo effects of this method through sciatic nerve injection.

(2) Compared with conventional liposomes, the local anesthesia time of anesthetic tetrodotoxin (TTX) encapsulated by methyl branched liposomes can be significantly prolonged to 70 hours, while the local anesthesia time of conventional liposomes is only 16 hours. In summary, this research work fully demonstrates the effectiveness of methyl branched liposomes as a reservoir system to achieve continuous drug delivery.

Case Study 2

In this case, the authors designed a construction strategy for tandem and in situ combinatorial synthesis of degradable branched-chain (DB) lipidoids based on a one-pot, two-step, three-component reaction (3-CR). In this design, two branched tails are attached in situ to an inactive aminoalcohol lipid containing two short body tails via a degradable linker, which greatly facilitates mRNA delivery. By varying the headgroup structure, body-tail length, and branch-tail length, the researchers systematically synthesized and screened two DB-lipid combinatorial libraries.

Fig. 2. In situ combinatorial synthesis and mRNA delivery of degradable branched lipidoids (Nat Commun. 2024, 15: 1762).

The authors found that the mRNA delivery efficiency can be improved by three orders of magnitude by attaching the branch tail to the invalid lipid by the degradable linker. The combinatorial screening and systematic study of two DB-lipid libraries revealed important structural criteria for controlling their in vivo efficacy. Major DB-LNP demonstrated that mRNA therapeutics and gene editors can be delivered powerfully to the liver. In a diet-induced obese mouse model, the authors found that repeated administration of DB-LNP encapsulating mRNA encoding human fibroblast growth factor 21 alleviated obesity and fatty liver.

References

1. Yang, L. et al. Methyl-Branched Liposomes as a Depot for Sustained Drug Delivery. Nano Lett. 2023, 23(20): 9250-9256.
2. Han, X. et al. In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors. Nat Commun. 2024, 15: 1762.