Increased bioavailability of rifampicin from stimuli-responsive smart nano carrier.

Stimuli responsive polymeric nanocarrier (RCOP-2) functionalized with frontline antituberculosis drug (Rifampicin) is demonstrated for sustained release. Bioavailability of Rifampicin is taken care of by conjugating this drug through a acylhydrazine linker to the polymeric backbone. The poly(ethylene glycol) structural motif is introduced in the copolymer architecture for water solubility. Releasing retinal along with Rifampicin is hypothesized to reduce the risk of side effects due to Rifampicin. The self-assembly of RCOP-2, due to the amphiphilicity present in the copolymer, is explored in detail. The pH responsiveness of RCOP-2 is demonstrated in mild acidic environment as well as in cell lines. The 4T cell line, due to its acidic nature, shows time-dependent cellular internalization. On the basis of the results, our unique design is expected to provide an increased bioavalaibility of Rifampicin with reduced side effects. From the flow cytometry results on A549 cell lines, it is clear that the newly designed copolymer RCOP-2 can internalize efficiently and serve as an effective Rifampicin delivery system.

[1]  R. Shunmugam,et al.  Stimuli responsive nanocarrier for an effective delivery of multi-frontline tuberculosis drugs , 2014 .

[2]  R. Shunmugam,et al.  Hierarchical Self-Assembly of Amphiphilic Homopolymer into Unique Superstructures. , 2014, ACS macro letters.

[3]  R. Shunmugam,et al.  Amphiphilic Homopolymer Vesicles as Unique Nano-Carriers for Cancer Therapy , 2012 .

[4]  R. Shunmugam,et al.  A unique polymeric nano-carrier for anti-tuberculosis therapy , 2012 .

[5]  Ting Xu,et al.  Long-circulating 15 nm micelles based on amphiphilic 3-helix peptide-PEG conjugates. , 2012, ACS nano.

[6]  R. Shunmugam,et al.  Reversible pH- and Lipid-Sensitive Vesicles from Amphiphilic Norbornene-Derived Thiobarbiturate Homopolymers. , 2012, ACS macro letters.

[7]  H. Smyth,et al.  Controlled Pulmonary Drug Delivery , 2011 .

[8]  G. J. Gabriel,et al.  Self-activation in de novo designed mimics of cell-penetrating peptides. , 2011, Angewandte Chemie.

[9]  Chunsheng Xiao,et al.  Synthesis of amphiphilic alternating polyesters with oligo(ethylene glycol) side chains and potential use for sustained release drug delivery. , 2011, Biomacromolecules.

[10]  Sabine Ehrt,et al.  Acid Resistance in Mycobacterium tuberculosis , 2009, Journal of bacteriology.

[11]  W. DeGrado,et al.  New design of helix bundle peptide-polymer conjugates. , 2008, Biomacromolecules.

[12]  V. Pillay,et al.  Tuberculosis chemotherapy: current drug delivery approaches , 2006, Respiratory research.

[13]  L. Yahia,et al.  Therapeutic potential of nanoparticulate systems for macrophage targeting. , 2005, Biomaterials.

[14]  K. Ulbrich,et al.  Polymeric anticancer drugs with pH-controlled activation. , 2004, Advanced drug delivery reviews.

[15]  D. Prabakaran,et al.  Osmotically regulated asymmetric capsular systems for simultaneous sustained delivery of anti-tubercular drugs. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Rajesh Pandey,et al.  Poly (DL-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis. , 2003, The Journal of antimicrobial chemotherapy.

[17]  R. Grubbs.  Handbook of metathesis , 2003 .

[18]  L. Amzel,et al.  Tuberculosis drug targets. , 2002, Current drug targets.

[19]  S. Nguyen,et al.  Toward Polymeric Anticancer Drug Cocktails from Ring-Opening Metathesis Polymerization , 2001 .

[20]  A. Chakraborti,et al.  The Reason for an Increase in Decomposition of Rifampicin in the Presence of Isoniazid under Acid Conditions , 2000 .

[21]  R. Grubbs,et al.  Synthesis of Norbornenyl Polymers with Bioactive Oligopeptides by Ring-Opening Metathesis Polymerization , 2000 .

[22]  J. Patton,et al.  Mechanisms of macromolecule absorption by the lungs , 1996 .

[23]  Peter R. Byron,et al.  Inhaling medicines: delivering drugs to the body through the lungs , 2007, Nature Reviews Drug Discovery.

[24]  Ying Zhang,et al.  New drug candidates and therapeutic targets for tuberculosis therapy. , 2006, Drug discovery today.

[25]  J. Hamman,et al.  Oral delivery of peptide drugs: barriers and developments. , 2005, BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy.

[26]  J. Patton,et al.  The lungs as a portal of entry for systemic drug delivery. , 2004, Proceedings of the American Thoracic Society.

[27]  S. Ferebee.  Controlled chemoprophylaxis trials in tuberculosis. A general review. , 1970, Bibliotheca tuberculosea.

[28]  Ferebee Sh.  Controlled chemoprophylaxis trials in tuberculosis. A general review. , 1970 .