Advances in Life-Saving Approach of Anti-Tuberculosis Drugs Delivery by Nanoparticles Over Free Drugs

1. Shifa Killedar1 and *Basavaraj Madhusudhan2.
1.Department of Food Technology, Davangere University, Davangere – 577 007, Karnataka, India.
2. Research Center for Nanoscience and Technology, Department of Biochemistry and Food
Technology, Davangere University, Shivagangothri, Davangere- 577007, Karnataka, India.
Email: shifa.killedar@gmail.com; prof.madhusudhan@gmail.com
Oral presentaion in national seminar on “LIFESCIENCEFORTHELIFE”

2. CONTENTS:
1. Introduction
2. Different forms of TB
3. Multi-drug resistant tuberculosis (MDR-TB) & Extensively Drug
Resistant tuberculosis (EDR-TB)
4. Side-effects
5. Nanotechnology based therapies
6. Liposomes based drug delivery
7. Advantages over free drugs.
8. Oral delivery of ligand conjugated site-targeted pulmonary
delivery of nanomedicine
9. Conclusion and Future prospective
10. Acknowledgement .
11. References

3. INTRODUCTION:
TUBERCULOSIS-2nd most fatal
infectious disease.
Prolonged treatment,high-pill
Burden,development of MDR-TB;
Results in INTOLERABLE SIDE
EFFECTS AND TOXICITY.
Challenge- Effective & Robust
System To Reduce Technical Drawbacks & improve the effectiveness of
therapeutic drugs.
Anti-tb Drug Delivery Through Nanoparticles Has Shown Convincing
Treatment And Promising Outcome.

4. MYCOBACTERIUM TUBERCULOSIS

6. MULTIDRUG-RESISTANT TUBERCULOSIS (MDR-TB):
 Defined by resistance to at least two of the standard four drug
anti-TB medicines.
 Inadequate or inconsistent treatment has allowed MDR-TB to emerge
and spread quickly.
 Treatment-almost two years(involves daily injections)
 Complex, Expensive, And Toxic,Patients Struggle
To Live .
 Second-line Lethal; Harsh Side Effects.
Extensively Drug-Resistant TB (XDR-TB):
 more brutal form of MDR-TB.
 characterized by resistance to any fluoroquinolone and at least one of
the three injectable second-line drugs-PROBLEMATIC TREATMENT.
 52 out of 53 -died within few months.
 70% of XDR-TB patients were estimated to die within a month of
diagnosis.

7. CONVENTIONAL MODE OF TREATMENT:
 Drug-distributed throughout the
body via the systemic blood
circulation and a majority of
molecules do not reach their
targets & consequently, stay in the
body causing adverse side effects.
 Drugs have a short plasma-life and
rapid clearance, which limits their
effectiveness.
 Time consuming process.
 Costly.
 Require frequent visits for
treatment.
 Hair fall
 Sterility in men; miscarriage in
female.
 Haemolysis Anemia, vertigo etc.
SIDE-EFFECTS: DISADVANTAGES:

9. NANOTECHNOLOGY-BASED THERAPIES:
 NANOPARTICLE CHARACTERISATION- Particle Size(100-500nm),
Density, Surface Properties.
 MODE OF DRUG DELIVERY: Oral ; Intravenous Delivery of ATD
Nanomedicine,Pulmonary Delivery.
 LIPID DRUG DELIVERY SYSTEMS:

10. LIPOSOME-BASED DRUG DELIVERY SYSTEMS:
 Miniature closed vesicles consisting of phospholipid bilayer enfolding an
aqueous section.
 Alternating hydrophilic and hydrophobic structure-capacity to entrap compounds
of different solubilities.
 Amenable to extensive modification or 'tailoring'
 Upon administering Mtb infected mice twice a week for 6 weeks, it was observed
that liposomes encapsulated drugs (rifampicin) were more powerful in clearing
mycobacterial infection when compared to the free drugs.

11. THE ADVANTAGES OF NANOCARRIERS:
 Ability to control and targeted drug delivery
 Nil to less side effects.
 improve stability of pharmaceuticals.
 Ability to encapsulate high drug content (ex.Polymeric nanoparticles).
 carry both lipophilic and hydrophilic drugs.
 Biodegradable,excellent biocompatibility, non-toxic, non-allergenic & non-
irritating.
 Formulated by water-based technologies-can avoid organic solvents.
 Easy to scale‐up and sterilize.
 Less expensive.
 Easy to validate.
 Drug retention is unlikely.

12. ORAL DELIVERY OF LIGAND CONJUGATED,SITE TARGETED DELIVERY OF NANO
MEDICINES:
 Far superior to the delivery of free drugs in terms of bioavialability, residence time,
and biodistribution.
 Choicest route for drug administration - Non-invasive nature.
 Rifampin, Isoniazid, And Pyrazinamide-prepared by solvent evaporation method
and by double emulsion process; encapsulated by PLG NPs.
 Drug levels were maintained & after a single oral administration of drug-loaded
PLG Nps for 6 to 9 days in the plasma.
 Free drugs were vacant from plasma within 12–24 hours.
 Complete bacterial clearance,nanoparticle
(5 oral doses every 10th day).
 46 doses were free drugs able to
generate same cause.
 Guinea pigs-similar findings.

13. SITE SPECIFIC TARGETED DRUG DELIVERY MECHANISM:

14. CONCLUSION:
 In developing and underdeveloped countries, infectious diseases are foremost
issues of health concern.
 1/3rd population-does not have proper access to vital medicines.
 TB being one of the main threat.
 Goal- find out a solution to eradicate the transmission of causative
organism (multifarious, and thorny due to the difficulty of diagnosis, multidrug
resistance, and patients’ low compliance to treatment)
 Drugs-quinolones and rifamycins only available.
 Advancements in the nanoparticle based delivery systems -commercial,
practical, promising substitute for potential TB chemotherapy.
 Various Advantages.
 Appropriate clinical studies should be done in order to find out whether or
not nanoparticle-based drug delivery system might be much anticipated
solution for improving the patient compliance in TB chemotherapy.

15. ACKNOWLEDGEMENT:
 The Authors are thankful to DST-SERB, New Delhi
and Davangere University, Karnataka, India for help
with the Project work being carried out.
 I specially thank my guide prof.Basavraj
madhusudhan,for his active support and guidance.

16. REFERENCES:
 A. M. Cooper, “Cell-mediated immune responses in tuberculosis,”
Annual Review of Immunology, vol. 27, pp. 393–422, 2009.
 K. Rohde, R. M. Yates, G. E. Purdy, and D. G. Russell,
“Mycobacterium tuberculosis and the environment within the
phagosome,” Immunological Reviews, vol. 219, no. 1, pp. 37–54,
2007.
 G. R. Stewart, B. D. Robertson, and D. B. Young, “Tuberculosis: a
problem with persistence,” Nature Reviews Microbiology, vol. 1, no.
2, pp. 97–105, 2003.
 WHO Global Tuberculosis Control Report 2010, “Summary,” Central
European Journal of Public Health, vol. 18, no. 4, p. 237.
 Other internet sources.