- A platform for the efficient entrapment and targeted release of small hydrophobic drug molecules
- Individual drug molecules are imbedded within the hydrophobic crystal structure of histidine and are only released when the crystal is dissolved in aqueous conditions
- This system has been tested in vitro for the entrapment of doxorubicin, an anticancer drug, and release in the presence of hyaluronidase, acting as a proxy for drug delivery to tumor cells with overexpressed CD44-receptors.
A platform enabling the efficient entrapment of small, hydrophobic pharmaceutical molecules inside histidine crystals, for targeted site-specific drug delivery
Many hydrophobic drug molecules of interest are abandoned during preclinical studies due to poor water solubility. Despite any promising in vitro therapeutic effects, insoluble drug molecules tested in vivo can lead to low bioavailability, toxic accumulation, and the exacerbation of undesired side effects. Thus, strategies to improve hydrophobic drug solubility or target molecule delivery can expand known repertoires of drug treatments.
Current drug delivery systems typically rely on lipid or polymer-based carriers that encapsulate or covalently bond with hydrophobic drug molecules. These timed-release scaffolds can be metabolized at a predictable rate, releasing the drug molecules within. However, most lipid and polymer-based systems suffer from a lack of site-specificity, low biocompatibility, and inefficient drug entrapment. These disadvantages often lead to therapeutic failure, increasing drug loading that could cause unpredictable side effects.
Cornell inventors have created a platform for the efficient entrapment and targeted release of small hydrophobic drug molecules within crystals of L-histidine, a highly biocompatible essential amino acid. Individual drug molecules are embedded within the hydrophobic crystal structure of histidine and are only released when the crystal is dissolved in aqueous conditions. By functionalizing the surface of the crystal (e.g., with hyaluronic acid), this delivery system can be tailored to be site-specific for targeted drug release (e.g., in the presence of hyaluronidase). Additionally, histidine crystals have inherent fluorescent properties, permitting experimentalists and clinicians to track and monitor drug delivery within biological systems. This system has been tested in vitro for the entrapment of doxorubicin, an anticancer drug, and release in the presence of hyaluronidase, acting as a proxy for drug delivery to tumor cells with overexpressed CD44-receptors.
- Utilizes a highly biocompatible essential amino acid scaffolding, rather than lipid or polymer-based carriers
- Physical inclusion of drug molecules, rather than covalent bonding, retains drug efficacy
- Increases the water solubility of hydrophobic drug molecules
- Crystal surface modification can be tailored for site-specific drug delivery
- Entrapment of doxorubicin for the site-specific delivery of anticancer drugs to tumor cells
- Any variety of small hydrophobic drug molecules can be efficiently loaded within the histidine crystal structure
- Fluorescent monitoring of drug delivery within biological systems
Ravanfar, R., Abbaspourrad, A. 2019. L-Histidine Crystals as Efficient Vehicles to Deliver Hydrophobic Molecules. ACS Applied Materials & Interfaces. 11 (42), 39376-39384. https://doi.org/10.1021/acsami.9b14239
Name: Aris Despo