Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent.
The purpose of the present investigation was to evaluate the potential of surface engineered polypropylene imine (PPI) dendrimers as nanoscale drug delivery units for site-specific delivery of a model anti-cancer agent, doxorubicin.hydrochloride (DOX). Dextran conjugated PPI dendrimers were synthesized, characterized and further loaded with DOX. The developed formulation was characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and transmission electron microscopic (TEM) studies. Dendrimer formulation was evaluated for in vitro drug release and haemolytic studies under various pH conditions. Cell uptake and cytotoxicity studies were performed on A549 cell lines using MTT cell proliferation assay. In vivo studies were conducted for evaluation of various pharmacokinetic parameters and tissue distribution pattern. In vitro, formulation displayed initial rapid release of the drug followed by rather slow release. Further, the dextran conjugated dendrimer formulation was found to be least haemolytic but more cytotoxic as compared to free drug. Cell uptake studies depicted that the formulation was preferably taken up by the tumor cells when compared to free drug. The conjugation of oxidized polyaldehyde dextran imparts macromolecular nature to the dendritic carrier, consequently the formulation was found to selectively enter highly porous mass of tumor cells at the same time precluding normal tissues. Thus it was concluded that the drug loaded dendrimer formulation would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.
Agarwal
Abhinav
A
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar 470003, Madhya Pradesh, India.
Gupta
Umesh
U
Asthana
Abhay
A
Jain
Narendra K
NK
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D050091:Dendrimers; D003911:Dextrans; D004337:Drug Carriers; D004317:Doxorubicin