Dendrimers

Dendrimers are highly branched globular macromolecules. Several researchers have exploited the multivalency of dendrimers at the periphery for attachment of drug molecules. A significant advantage of this system is that the drug loading can be tuned by varying the generation

Linker Carrier Drug

Linker Carrier Drug

of the dendrimer, and the release of drug can be tailored by incorporating degradable linkages between the drug and the dendrimer.123 Conjugates of poly(amidoamine) (PAMAM) dendrimers with cisplatin have been shown to improve aqueous solubility and to reduce systemic toxicity while simultaneously exhibiting selective accumulation in tumors.124 Propranolol is a poorly soluble drug and is a known substrate of the P-glycoprotein (P-gp) efflux transporter. A prodrug of propranolol was synthesized by conjugating propranolol to generation 3 (G3) and lauroyl-G3 PAMAM dendrimers. Both derivatives demonstrated improved aqueous solubility and bypassed the efflux transporter with improved bioavailability.125

Hep-Direct liver-targeted therapy126 represents a novel class of phosphate and phosphonate prodrugs that are cyclic 1,3-propanyl esters containing a ring substituent that renders them sensitive to an oxidative cleavage reaction catalyzed by a cytochrome P450 within hepatocytes. This platform may be useful for treating chronic liver diseases such as hepatitis and hepatocellular carcinoma with reduced systemic exposure and side effects. The authors have demonstrated liver targeting of nucleotide analogues adefovir and cytarabine (Ara-C).

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