Abstract
In spite of numerous biopharmaceutical applications of fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability. Maximum biocompatibility with minimal toxicity is the key rationale for an ideal drug-delivery system. Keeping this principle in mind, the present investigation aimed to explore the tumor-targeting potential of folate-engineered fourth-generation PPI dendrimers loaded with an anticancer drug, melphalan. Fourth-generation PPI as well as folate-conjugated fourth-generation PPI dendrimers were synthesized, characterized and loaded with melphalan. Hemolytic toxicity, cytotoxicity, cellular uptake and fluorescence uptake studies reveal that the developed folate-conjugated derivative has significantly lower toxicity, as well as demonstrates folate receptor specificity. The developed nanoconjugates appear to be proficient in carrying as well as site-specific delivery of melphalan, with an improved therapeutic margin and improved safety.
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