Galactomannan-PEI based non-viral vectors for targeted delivery of plasmid to macrophages and hepatocytes.
Intracellular nature and diversified locations of infectious and parasitic diseases such as leishmaniasis, trypanosomiasis, tuberculosis and hepatitis B and C pose a significant global burden and challenge to the scientists working in the area of drug discovery and drug delivery. The macrophages and hepatocytes are considered as potential target sites as they together play an important role in various infectious diseases. The present study scrutinizes the applicability of a natural biopolymer-based chemical vectors, capable of targeting both macrophages and hepatocytes, that can form a complex with plasmid and administer it into cells to produce a desired protein. The investigations were made to develop a novel series of gene carriers by conjugating depolymerized galactomannan (guar gum), a biocompatible polysaccharide with low molecular weight branched PEI (LMWP). A series of conjugates were developed and characterized using physicochemical techniques. All the GP/pDNA complexes showed significantly higher transfection efficiency with GP-3/pDNA, one of the best formulations, showed ~2.0-7.7-folds higher transfection efficacy when compared with the standard transfection reagents. Further, GP-3/pDNA displayed significantly higher target specific transfection efficiency under both in vitro and in vivo conditions. The data demonstrate the potential of GP vectors to deliver nucleic acids simultaneously to macrophages and hepatocytes in gene delivery applications.
CSIR-Institute of Genomics and Integrative Biology, Delhi, India; Academy of Scientific and Innovative Research, New Delhi, India.
Ruby
R
Bansal
CSIR-Indian Institute of Toxicology Research, Lucknow, India.
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AK
Singh
Indian National Science Academy, New Delhi, India.
R P
RP
Gandhi
CSIR-Indian Institute of Toxicology Research, Lucknow, India.
A B
AB
Pant
CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
P
P
Kumar
CSIR-Indian Institute of Toxicology Research, Lucknow, India; CSIR-Institute of Genomics and Integrative Biology, Delhi, India. Electronic address: kcgupta@iitr.res.in.
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KC
Gupta
D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005685:Galactans / Q000008:administration & dosage / Q000737:chemistry; D005690:Galactose / Q000031:analogs & derivatives; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000737:chemistry; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008351:Mannans / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D010316:Particle Size; D053149:Plant Gums / Q000008:administration & dosage / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry; D014162:Transfection / Q000379:methods
D004337:Drug Carriers; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D011134:Polysaccharides; C012990:galactomannan; D004247:DNA; C007894:guar gum; D005690:Galactose
Galactomannan; Gene delivery; Hepatocytes; In vitro; In vivo; Macrophages; Polyethylenimine