FORMULATION, OPTIMIZATION, AND CHARACTERIZATION OF BIOCOMPATIBLE INHALABLE D-CYCLOSERINE-LOADED ALGINATE-CHITOSAN NANOPARTICLES FOR PULMONARY DRUG DELIVERY

  • Jessy Shaji Department of Pharmaceutics, Prin. K. M. Kundnani College of Pharmacy, 23, Jote Joy Building, RambhauSalgaonkar Marg, Cuffe Parade, Mumbai 400005, India http://orcid.org/0000-0001-6661-4943
  • Mahmood Shaikh Department of Pharmaceutics, Prin. K. M. Kundnani College of Pharmacy, 23, Jote Joy Building, RambhauSalgaonkar Marg, Cuffe Parade, Mumbai 400005, India

Abstract

ABSTRACT
Objective: To prepare Nanoparticulate dosage form having improved drug bioavailability and reduced dosing frequency of antitubercular drugs
which will helps in improving patient compliance in the treatment of multi-drug resistant tuberculosis (MDR-TB).
Methods: Ionotropic gelation method was used to prepare D-cycloserine (D-CS)-loaded alginate-chitosan nanoparticles, and the particles are
characterized by their particle size and morphology using particle size analyzer and scanning electron microscopy (SEM). X-ray diffraction (XRD),
differential scanning calorimetry (DSC), and Fourier-transformed infrared (FTIR) studies were used to determine drug-polymer interactions and drug
entrapment. Entrapment efficiency, drug loading (DL), particle size, and zeta potential of nanoparticles were also studied. The 2
factorial designs of
experiments by Design-Expert
®
V9 were used to optimize the particle size and entrapment efficiency of nanoparticles.
Results: The optimized batch had shown the entrapment efficiency of 98.10±0.24% and DL of 69.32±0.44% with particle size and zeta potential
as 344±5 nm and −42±11.40 mV, respectively. DSC, FTIR, and XRD studies confirmed the drug entrapment within nanoparticle matrix. SEM results
showed spherical-shaped particles. Sustained release of drug from the nanoparticles was observed for 24 hrs period. Respirable fraction up to
52.37±0.7% demonstrates the formulation suitability for deep lung delivery. Lung inflammatory study showed a less inflammatory response.
Conclusion: Ionotropic gelation method can be used to prepare biocompatible particles with a high entrapment efficiency, DL, optimum particle size,
and controlled release characteristics, which can serve as a convenient delivery system for D-CS and could be a potential alternative to the existing
conventional therapy in MDR-TB.
Keywords: Nanoparticles, Alginate, Chitosan, Inhalation, Sustained release, Tuberculosis.
3

Author Biographies

Jessy Shaji, Department of Pharmaceutics, Prin. K. M. Kundnani College of Pharmacy, 23, Jote Joy Building, RambhauSalgaonkar Marg, Cuffe Parade, Mumbai 400005, India
Professor, Dept. of Pharmaceutics
Mahmood Shaikh, Department of Pharmaceutics, Prin. K. M. Kundnani College of Pharmacy, 23, Jote Joy Building, RambhauSalgaonkar Marg, Cuffe Parade, Mumbai 400005, India
M.Pharm Research Student, Dept. of Pharmaceutics

References

REFERENCES
1. Dye C, Watt CJ, Bleed DM, Hosseini SM, Raviglione MC.
Evolution of tuberculosis control and prospects for reducing
tuberculosis incidence, prevalence, and deaths globally. JAMA
2005;293(22):2767-75.
2. Gelperina S, Kisich K, Iseman MD, Heifets L. The potential advantages
of nanoparticle drug delivery systems in chemotherapy of tuberculosis.
Am J Respir Crit Care Med 2005;172(12):1487-90.
3. Faustini A, Hall AJ, Perucci CA. Risk factors for multidrug resistant
tuberculosis in Europe: A systematic review. Thorax 2006;61(2):158-63.
4. Grosset JH, Singer TG, Bishai WR. New drugs for the treatment
of tuberculosis: Hope and reality. Int J Tuberc Lung Dis
2012;16(8):1005-14.
5. Li P, Dai YN, Zhang JP, Wang AQ, Wei Q. Chitosan-alginate
nanoparticles as a novel drug delivery system for nifedipine. Int J
Biomed Sci 2008;4(3):221-8.
6. Justo OR, Moraes AM. Kanamycin incorporation in lipid vesicles
prepared by ethanol injection designed for tuberculosis treatment.
J Pharm Pharmacol 2005;57(1):23-30.
7. Irache JM, Merodio M, Arnedo A, Camapanero MA, Mirshahi M,
Espuelas S. Albumin nanoparticles for the intravitreal delivery of
anticytomegaloviral drugs. Mini Rev Med Chem 2005;5(3):293-305.
8. Umamaheshwari RB, Ramteke S, Jain NK. Anti-Helicobacter
pylori effect of mucoadhesive nanoparticles bearing amoxicillin in
experimental gerbils model. AAPS PharmSciTech 2004;5(2):e32.
9. Pandey R, Ahmad Z, Sharma S, Khuller GK. Nano-encapsulation of
azole antifungals: Potential applications to improve oral drug delivery.
Int J Pharm 2005;301(1-2):268-76.
10. Lucinda-Silva RM, Evangelista RC. Microspheres of alginate-chitosan
containing isoniazid. J Microencapsul 2003;20(2):145-52.
11. Khuller GK, Kapur M, Sharma S. Liposome technology for
drug delivery against mycobacterial infections. Curr Pharm Des
2004;10(26):3263-74.
12. Qurrat-ul-Ain, Sharma S, Khuller GK, Garg SK. Alginate-based
oral drug delivery system for tuberculosis: Pharmacokinetics and
therapeutic effects. J Antimicrob Chemother 2003;51(4):931-8.
13. Pandey R, Khuller GK. Chemotherapeutic potential of alginate-chitosan
microspheres as anti-tubercular drug carriers. J Antimicrob Chemother
2004;53(4):635-40.
14. Xiong MH, Bao Y, Yang XZ, Zhu YH, Wang J. Delivery of antibiotics
with polymeric particles. Adv Drug Deliv Rev 2014;78:63-76.
15. Mi FL, Sung HW, Shyu SS. Drug release from chitosan- alginate
complex beads reinforced by a naturally occurring crosslinking agent.
Carbohydr Polym 2002;48(1):61-72.
16. Coppi G, Iannuccelli V, Leo E, Bernabei MT, Cameroni R. Protein
immobilization in crosslinked alginate microparticles. J Microencapsul
2002;19(1):37-44.
17. Kulkarni PV, Keshavayya J. Chitosan – Sodium alginate biodegradable
Interpenetrating Polymer Network (IPN) beads for delivery of ofloxacin
hydrochloride. Int J Pharm Pharm Sci 2010;2 Suppl 2:77-82.
18. Reddy BV, Kumar KH, Chandra SR, Chandra AS, Babu GD, Chandra P.
Preparation and in-vitro evaluation of ofloxacin mucoadhesive
microspheres. Int J Pharm Pharm Sci 2012;4(1):93-6.
19. Sathali AA, Varun J. Formulation, development and in vitro evaluation
of candesartan cilexetil mucoadhesive microbeads. Int J Curr Pharm
Res 2012;4(3):109-18.
20. V’Ooteghem MM. In: Edman P, editor. Biopharmaceutics of Ocular
Drug Delivery. Boca Raton: CRC Press; 1993. p. 27-41.
21. Rajaonarivony M, Vauthier C, Couarraze G, Puisieux F, Couvreur P.
Development of a new drug carrier made from alginate. J Pharm Sci
1993;82(9):912-7.
22. Arora S, Gupta S, Narang RK, Budhiraja RD. Amoxicillin
loaded chitosan-alginate polyelectrolyte complex nanoparticles
as mucopenetrating delivery system for H. Pylori. Sci Pharm
2011;79(3):673-94.
23. Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ,
Khar RK. Chitosan-sodium alginate nanoparticles as submicroscopic
reservoirs for ocular delivery: Formulation, optimisation and in vitro
characterisation. Eur J Pharm Biopharm 2008;68(3):513-25.
24. Mali AJ, Pawar AP, Purohit RN. Development of budesonide loaded
biopolymer based dry powder inhaler: Optimization, in vitro deposition,
and cytotoxicity study. J Pharm (Cairo) 2014;2014:795371.
25. Jabłczyńska K, Janczewska M, Kulikowska A, Sosnowski T. Preparation
and characterization of biocompatible polymer particles as potential
nanocarriers for inhalation therapy. Int J Polym Sci 2015;2015:1-8.
26. Kondej D, Sosnowski TR. Changes in the activity of the pulmonary
surfactant after contact with bentonite nanoclay particles. Chem Eng
Trans 2012;26:531-6.
27. Mann JF, McKay PF, Arokiasamy S, Patel RK, Klein K, Shattock RJ.
Pulmonary delivery of DNA vaccine constructs using deacylated PEI
elicits immune responses and protects against viral challenge infection.
J Control Release 2013;170(3):452-9.
28. Sarmento B, Ferreira D, Veiga F, Ribeiro A. Characterization of insulinloaded
alginate nanoparticles produced by ionotropic pre-gelation
through
DSC and FTIR studies. Carbohydr Polym 2006;66(1):1-7.
29. Malesu VK, Sahoo D, Nayak PL. Chitosan-sodium alginate
nanocomposites blended with cloisite 30b as a novel drug delivery
system for anticancer drug curcumin. Int J Appl Biol Pharm Technol
2011;2(3):402-11.
30. Emami J, Boushehri MS, Varshosaz J. Preparation, characterization and
optimization of glipizide controlled release nanoparticles. Res Pharm
Sci 2014;9(5):301-14.
31. Desai TR, Hancock RE, Finlay WH. A facile method of delivery of
liposomes by nebulization. J Control Release 2002;84(1-2):69-78.
32. Matilainen L, Järvinen K, Toropainen T, Näsi E, Auriola S, Järvinen T,
et al. In vitro evaluation of the effect of cyclodextrin complexation
on pulmonary deposition of a peptide, cyclosporin A. Int J Pharm
2006;318(1-2):41-8.
33. Haberl N, Hirn S, Wenk A, Diendorf J, Epple M, Johnston BD,
et al. Cytotoxic and proinflammatory effects of PVP-coated silver
nanoparticles after intratracheal instillation in rats. Beilstein J
Nanotechnol 2013;4:933-40.
34. Neupane YR, Sabir MD, Ahmad N, Ali M, Kohli K. Lipid drug
conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery
of decitabine: Ex vivo gut permeation studies. Nanotechnology
2013;24(41):415102.
35. Patel JK, Patel RP, Amin AF, Patel MM. Formulation and evaluation
of mucoadhesive glipizide microspheres. AAPS PharmSciTech
2005;6(1):E49-55.
36. Gazori T, Khoshayand MR, Azizi E, Yazdizadeh PN, Nomani A,
Haririan I. Evaluation of alginate/chitosan anoparticles as antisense
delivery vector: Formulation, optimization and in vitro characterization.
Carbohydr Polym 2009;77(3):599-606.
37. Sartori C, Finch D, Ralph B, Gilding K. Determination of the
cation content of alginate thin films by FTIR spectroscopy. Polymer
1997;38(1):43-51.
38. Sankalia MG, Mashru RC, Sankalia JM, Sutariya VB. Reversed
chitosan-alginate polyelectrolyte complex for stability improvement
of alpha-amylase: Optimization and physicochemical characterization.
Eur J Pharm Biopharm 2007;65(2):215-32.
39. Chen SC, Wu YC, Mi FL, Lin YH, Yu LC, Sung HW. A novel pH-
sensitive hydrogel composed of N,O-carboxymethyl chitosan and
alginate cross-linked by genipin for protein drug delivery. J Control
Release 2004;96(2):285-300.
40. Yoksan R, Jirawutthiwongchai J, Arpo K. Entrapment of ascorbyl
94
Asian J Pharm Clin Res, Vol 9, Suppl. 2, 2016, 82-95
Shaji and Shaikh
palmitate in chitosan nanoparticles by oil-in-water emulsion and ionic
gelation processes. Colloids Surf B Biointerfaces 2010;76(1):292-7.
41. Qi L, Xu Z, Jiang X, Hu C, Zou X. Preparation and antibacterial activity
of chitosan nanoparticles. Carbohydr Res 2004;339(16):2693-700.
42. Zhang LF, Yang DJ, Chen HC, Sun R, Xu L, Xiong ZC, et al. An
ionically crosslinked hydrogel containing vancomycin coating
on a porous scaffold for drug delivery and cell culture. Int J Pharm
2008;353(1-2):74-87.
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How to Cite
Shaji, J., and M. Shaikh. “FORMULATION, OPTIMIZATION, AND CHARACTERIZATION OF BIOCOMPATIBLE INHALABLE D-CYCLOSERINE-LOADED ALGINATE-CHITOSAN NANOPARTICLES FOR PULMONARY DRUG DELIVERY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 8, Oct. 2016, pp. 82-95, doi:10.22159/ajpcr.2016.v9s2.11814.
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