Galactomannan-PEI based non-viral vectors for targeted delivery of plasmid to macrophages and hepatocytes

• Published in: European journal of pharmaceutics and biopharmaceutics 2014-08, Vol.87 (3), p.461-471
• Main Authors: Bansal, Ruby, Singh, A.K., Gandhi, R.P., Pant, A.B., Kumar, P., Gupta, K.C.
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; DNA - genetics; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Delivery Systems - methods; Galactans - administration & dosage; Galactans - chemistry; Galactomannan; Gene delivery; Gene Transfer Techniques; Genetic Vectors - administration & dosage; Genetic Vectors - chemistry; Hep G2 Cells; Hepatitis B virus; Hepatocytes; Hepatocytes - drug effects; Humans; In vitro; In vivo; Macrophages; Macrophages - drug effects; Male; Mannans - administration & dosage; Mannans - chemistry; MCF-7 Cells; Mice; Mice, Inbred BALB C; Molecular Weight; Mycobacterium; Particle Size; Plant Gums - administration & dosage; Plant Gums - chemistry; Plasmids - administration & dosage; Plasmids - chemistry; Polyethylenimine; Polysaccharides - administration & dosage; Polysaccharides - chemistry; Transfection - methods
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2014.05.001

[Display omitted] •Galactomannan-low molecular weight PEI (GP) conjugates have been synthesized.•The best formulation, GP-3, efficiently carried pDNA inside the cells.•Galactomannan in GP conjugates induced higher target specific transfection efficiency.•Potential of GP vectors to deliver nucleic acids to both 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.