ABSTRACT
Doxorubicin is a broad spectrum anticancer antibiotic that possesses toxic effects such as cardiomyopathy, that even lead to congestive heart failure. Thus, the development of a new bio-inspired system is required, that retain the advantageous effect of doxorubicin while retarding the side effects. Hence, a system was developed that we describe 'doxorubicin-DNA adduct entrenched artificial virus encased in polypeptide complex'. The drug-DNA adduct (DDA) was prepared by a formaldehyde mediated reaction. A simple chloroform extraction method for the separation of DDA was developed. DDA was employed to self-assemble the folate tethered bovine serum albumin to form the protein coat in the proposed artificial virus. The folate tethered albumin provides an artificial virus concept, with tumor tissue targeting due to the presence of folate. The whole system was then encased in a pH-responsive polypeptide complex that dissolves in acidic pH, but not in basic pH. DDA was evaluated by UV-Vis spectrophotometry, spectrofluorimetry and high-performance liquid chromatography (HPLC). A promising drug release at physiological condition was observed from DDA. The developed system was evaluated by a developed and validated artificial cell apparatus that mimic the features of a cancer cell. The drug delivery system displayed a considerable amount of drug release within 24â¯h. Moreover, the developed artificial virus system reduced angiogenesis caused by tumor cells in chick chorioallantoic membrane. Histopathology of treated chicken heart slices demonstrated that the developed artificial virus system reduces the tissue deformation and apoptosis in heart tissue slices, thus providing a new approach to prevent Dox-induced cardiomyopathy.
Subject(s)
Antibiotics, Antineoplastic/chemistry , DNA Adducts/chemistry , Doxorubicin/chemistry , Drug Carriers/chemistry , Peptides/chemistry , Animals , Antibiotics, Antineoplastic/metabolism , Antibiotics, Antineoplastic/pharmacology , Cattle , Chickens , Chorioallantoic Membrane/drug effects , Chorioallantoic Membrane/metabolism , Drug Liberation , Folic Acid/chemistry , Humans , Hydrogen-Ion Concentration , MCF-7 Cells , Microscopy, Electron, Transmission , Neovascularization, Physiologic/drug effects , Peptides/metabolism , Peptides/pharmacology , Serum Albumin, Bovine/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
Viruses are potent pathogens that can effectively deliver the genetic material to susceptible host cells. This capability is beneficially utilized to successfully deliver the genetic material. However, the use of virus mediated gene delivery is considered divisive, because the potentially replicable genomes recombine or integrate with the cell DNA resulting in immunogenicity, ranging from inflammation to death. Thus, the need for potentially effective non-viral gene delivery vehicles arises. Non-viral vectors, protein only particles and virus like particles (VLP) can be constructed which contain all the necessary functional moieties. These resemble viruses and are called artificial or synthetic virus. The artificial virus eliminates the disadvantages of viral vectors but retain the beneficial effects of the viruses. Need for further functionalization can be avoided by this approach because incorporation of requisite agents such as cell ligands, membrane active peptides, etc. into proteins is possible. The protein- DNA complexes resemble bacterial inclusion bodies. Nucleic acids influence conformation of protein units which subsequently result in cell uptake and finally to the cell nucleus. Such tunable systems mimic the activities of infected viruses and are used for the safe and effective delivery of drugs and genetic material in gene therapy. The versatility, stability and biocompatible nature of artificial virus along with high transfection efficacy have made it favorite for gene delivery purposes, in addition to being useful for various biomedical and drug delivery applications.
