Customized Lipid Drug Conjugates Drug Delivery System Services

Lipid drug conjugates are based on liposomal systems, nanoparticle systems and lipid excipients to form a good drug carrier transport system, which can help improve drug permeability and bioavailability, and can be used as a new research direction for a variety of drug preparations. CD Formulation can provide customization of lipid drug conjugates and use the product in drug delivery system services. Our services include physicochemical testing of products, drug release behavior studies, etc. We offer a full range of high quality services and customized solutions.

Lipid-drug Conjugate Delivery Systems

Lipid-drug conjugates (LDCs) are drug molecules covalently modified with lipids. The binding of a lipid to a drug molecule increases the lipophilicity and also changes other properties of the drug. Based on the chemistry of the drug and lipid, LDCs can be synthesized using a variety of conjugation strategies and chemical junctions. The junction and conjugation method determines how the drug is released from the LDC and is critical to the optimal performance of the LDC. The lipid portion of the adjuvant can significantly enhance drug loading into the hydrophobic component of the delivery vehicle, resulting in formulations with high drug loading and excellent stability.

Fig.1 Schematic diagram of the lipid-drug conjugates (LDCs). (Husni et al., 2023)

• Benefits of Lipid Drug Conjugate

• Improved performance of orally administered drugs.
• Improves delivery of anticancer drugs - enhances tumor targeting and reduces toxicity, overcoming drug resistance.
• Facilitates penetration into the brain.
• Enhances delivery of gene drugs.
• Facilitates drug loading into delivery vehicles.
• Enables prolonged drug release.

• Ways and means of LDC covalent bonding

LDCs are usually composed of fatty acids, glycerides, and phospholipids, whose carboxyl, hydroxyl, or phosphate groups are the active sites for reactions, and these active functional groups are covalently bonded to the drug through acylation, aiming to increase the lipid solubility of the drug.

Customization of Lipid Drug Couples

CD Formulation offers customization services for lipid drug couples. A large number of insoluble lipid couples are prepared and then the drug is covalently bonded to fatty acids or esters or ethers. The LDCs obtained by this method can be used alone or processed in the same way as other lipid nanoparticles (e.g. SLN or NLC), and the lipid-drug coupling can be via covalent or non-covalent bonding interactions. LDCs with covalent bonds are usually prepared by a series of chemical reactions followed by dispersion or precipitation, where the chemical structure of the lipid carrier or drug contains at least 1 carboxyl group. During the chemical reaction, the carboxyl group is converted to an inactive carboxylic acid ester. For lipid carriers or drugs with alcohols or amines or carboxyl groups in their chemical structure, the drug can be coupled to a lipid having a glycerol group in its structure if the drug has a carboxyl group.

Under some preparative conditions, the drug is first converted to a salt and then reacted with a fatty acid, which is further recrystallized to give a pure LDC product, with intermediate linkages that do not affect the effect of the pre-drug.

• Analysis of LDC degradation in vivo

Usually, LDC should be stable and avoid metabolism under the action of gastric acid and intestinal digestive enzymes, but also be able to be hydrolyzed by relevant enzymes in blood and tissues to release the prodrug and function. CD Formulation can improve the pharmacokinetic properties of drugs by carefully designing drug-lipid conjugates.

Reference

1. Husni, P., et al. (2023) Tumor microenvironment stimuli-responsive lipid-drug conjugates for cancer treatment. International Journal of Pharmaceutics, 122942.