Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

Abstract

Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

PAMAM dendrimer - cell membrane interactions

“…Since then, it has been shown that G4-6 PAMAM dendrimers mimic the topology of micelles and their accessible interiors could be used to encapsulate small guest molecules, such as hydrophobic drugs [29]. The open, flexible structure of lower generation dendrimers (G0-3) and the rigid surface of high generation dendrimers due to steric branch crowding (G7-10) provided less efficient encapsulation [30].…”

“…In addition to encapsulation in the dendrimer interior, the terminal functional groups at the dendrimer periphery can be used for complexation and conjugation of larger molecules. For instance, drug molecules and targeting moieties have been covalently attached to dendrimer surfaces [29]. The reactive amine groups on the PAMAM dendrimer periphery have also been functionalised with folates [33] and carbohydrates (coined glycodendrimers) [34] for cell specific targeting.…”

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

“…Many compounds that are excellent candidates as potent drugs against some pathologies do not continue with more advanced studies, due to their limited aqueous solubility. In recent years, several researches have been focused to solubilize powerful hydrophobic drugs to increase their bioavailability [76]. Some research has been conducted on the study of physicochemical parameters such as, water solubility, LogP, polar surface area, and the number of hydrogen bond acceptor and hydrogen bond donors as a measurement to elucidate the drug molecules solubility grade [77].…”

Synthesis and pharmacokinetic study of poly(ethylene oxide) triazole dendrimers decorated with aminosteroids as anticancer agent

“…Conjugated drugs have a reduced metabolism and reduced renal clearance, which leads to an increase half‐life in the bloodstream . Nanocarriers can also improve the aqueous solubility of a hydrophobic drug, providing a higher bioactive drug concentration in the bloodstream . Interestingly, these PK improvements allow selective accumulation of nanocarriers in leaky hypervascularized tissues with poor lymphatic drainage such as tumors .…”