The delivery system of L-leucine in drug carriers

With excellent biocompatibility, hydrophobicity, and modifiability, L-leucine is widely used in drug carrier delivery systems—particularly in in-depth research on nano drug delivery systems and pulmonary dry powder inhaler carriers. It also exhibits unique advantages in targeted drug delivery systems. The specific research directions and achievements are as follows:

1. Polyesteramide Nano Drug Delivery System

This system is a key research direction for L-leucine in antitumor drug delivery. Researchers synthesize polyesteramide polymers containing ester and amide bonds by reacting L-leucine with diols, dicarboxylic acids, etc. The ester bonds endow the carrier with good biodegradability, while the amide bonds ensure its mechanical and thermodynamic stability.

The carrier can self-assemble into core-shell structured nanoparticles with a particle size of 90–110 nm via the nanoprecipitation method. When loading antitumor drugs such as doxorubicin, it significantly improves the solubility and drug-loading capacity of hydrophobic drugs.

Its hydrophilic shell extends the circulation time of nanoparticles in the bloodstream, promotes drug accumulation at tumor sites, and reduces the toxicity of chemotherapeutic drugs to normal tissues.

Additionally, by adjusting the structures of dicarboxylic acids and diols used in synthesis, a library of polymer carriers can be constructed to meet the delivery requirements of different antitumor drugs.

2. Pulmonary Dry Powder Inhaler Delivery System

L-leucine is maturely applied in the research of preparing dry powder inhalers via spray drying, serving as a key excipient to improve the aerosol performance of dry powders. Its hydrophobicity, derived from the four-carbon aliphatic nonpolar side chain, enables it to play a special role during spray drying:

During the atomization stage, it reduces the surface tension of aqueous raw materials, decreases the size of atomized droplets, and facilitates pulmonary absorption.

During the drying process, due to its small molecular weight and high diffusion coefficient, L-leucine rapidly enriches on the droplet surface and crystallizes to form a hydrophobic shell. This shell not only imparts a corrugated surface to the particles, reducing interparticle agglomeration, but also enhances drug stability.

Studies have shown that when the initial concentration of L-leucine is within a reasonable range, 10%–20% of particle surface coverage can be achieved, significantly improving drug aerosolization efficiency. For example, co-spray drying with drugs such as salbutamol sulfate and voriconazole improves the physical stability and pulmonary delivery efficiency of the drugs, providing an efficient administration route for the treatment of diseases such as asthma and chronic obstructive pulmonary disease (COPD).

3. PLGA-Conjugated Hybrid Solid Lipid Nanoparticle Delivery System

Focusing on tumor-targeted delivery, this system prepares conjugated hybrid solid lipid nanoparticles (conj-hSLNs) by coupling L-leucine with poly(lactic-co-glycolic acid) (PLGA), enabling targeted drug delivery to triple-negative breast cancer cells via the L-amino acid transporter system 1.

Using betulin as a model drug, the carrier addresses the problem of low bioavailability caused by poor water solubility and permeability of betulin.

Experimental data shows that the nanoparticles have a particle size of approximately 318.3 nm, with a cumulative drug release rate of 57.763% within 24 hours, and the half-maximal inhibitory concentration (IC₅₀) against MDA-MB-231 breast cancer cells is 67.73 μg/mL.

Compared with free drugs, this delivery system increases the peak plasma concentration, prolongs the half-life, significantly enhances drug accumulation at tumor sites within 2 hours, and effectively inhibits tumor volume growth after 3 weeks of treatment—providing a new idea for the targeted therapy of malignant tumors such as breast cancer.

4. Drug-Resistant Leukemia Targeted Delivery System

This research combines L-leucine polymer carriers with chemotherapeutic drugs to address drug resistance in leukemia treatment.

Studies have found that L-leucine polymer carriers can activate the mTOR signaling pathway and inhibit autophagy, a mechanism that enhances the cytotoxicity of chemotherapeutic drugs against drug-resistant leukemia stem cells.

When loaded with doxorubicin, the formed nanoparticles can precisely target drug-resistant leukemia cells and effectively eliminate them.

In addition, the carrier possesses both biocompatibility and biodegradability, and can assist treatment by regulating cellular metabolism—breaking the limitation of traditional drug carriers that only perform delivery functions, and achieving the dual effect of "carrier-assisted therapy + drug-induced cytotoxicity." This provides a novel strategy for the treatment of drug-resistant leukemia.