Study of influence of polymerization factors on formation of poly(butyl cyanoacrylate) nanoparticles and in vitro drug release kinetics

Authors

  • L HARIVARDHAN-REDDY Drug delivery research laboratory, Center of relevance and excellence in NDDS, Pharmacy Department, G.H. Patel building, M.S. University of Baroda, Vadodara-390002, Gujarat, India
  • RSR MURTHY Drug delivery research laboratory, Center of relevance and excellence in NDDS, Pharmacy Department, G.H. Patel building, M.S. University of Baroda, Vadodara-390002, Gujarat, India

Keywords:

Poly(butyl cyanoacrylate), Nanoparticle, Doxorubicin, Polymerization, Drug entrapment, Drug release

Abstract

Poly(butyl cyanoacrylate) nanoparticles were synthesized by dispersion polymerization and characterized by 1H-NMRspectroscopy, differential scanning calorimetry and transmission electron microscopy. Particle properties such as zetapotential and size, and the influence of concentration and type of stabilizer on particle size were studied. The influenceof polymerization factors such as monomer concentration, polymerization time and temperature on the particle size anddistribution, and their effect on entrapment efficiency of the nanoparticles was studied, using doxorubicin hydrochloride(DH) as a model drug. High monomer concentrations lead to the formation of larger particles with broad and bimodalsize distribution, and increased the drug entrapment. Polymerization at low temperatures resulted in smaller particles,and agglomeration was found at high temperature (60°C), with reduced drug entrapment. High polymerization times didnot show much influence on particle size, but increased the drug entrapment. Drug loading into nanoparticles was carried out by incorporation and adsorption techniques, and drug entrapment was determined. The nanoparticles loadedby incorporation and adsorption techniques showed rapid drug release in 0.001N HCl. Drug release from both types ofnanoparticles followed Higuchi equation. An attempt was also made to critically correlate the particle properties anddrug release behavior and emphasize its importance in various facets of drug delivery.

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References

Couvreur P, Kante B, Roland M, Guiot P, Bauduin P, Speiser P. Polycyanoacrylate nanocapsules as potential lysosomotropic

carriers: preparation, morphological and sorptive properties. J Pharm Pharmacol 1979; 3: 1331-1332.

Beck PH, Kreuter J, Muller EG, Schatton W. Improved peroral delivery of avarol with poly(butyl cyanoacrylate)

nanoparticles. Eur J Pharm Biopharm 1994; 40: 134-137.

Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA. Passage of peptides through the blood-brain barrier with colloidal

polymer particles (nanoparticles). Brain Res 1995; 674: 171-174.

Schroeder U, Sabel BA. Nanoparticles, a drug carrier system to pass the blood-brain barrier, permit central analgetic

effects of i.v. dalargin injections. Brain Res 1996; 710: 121-124.

Verdun C, Couvreur P, Vranckx H, Lenaerts V, Roland M. Development of a nanoparticle controlled-release formulation

for human use. J Cont Rel 1986; 3: 205-210.

Kreuter J. Physicochemical characterization of polyacrylic nanoparticles. Int J Pharm 1983; 14: 43-58.

Behan N, Birkinshaw C, Clarke N. Poly n-butyl cyanoacrylate nanoparticles: a mechanistic study of polymerization and

particle formation. Biomaterials 2001; 22: 1335-1344.

Marchal-Heussler I, Maincent P, Hoffman M, Spittler J, Couvreur P. Antiglaucomatous activity of betaxolol chlorhydrate

sorbed onto different isobutyl cyanoacrylate nanoparticle preparations. Int J Pharm 1990; 58: 115-122.

Brasseur N, Brault D, Couvreur P. Adsorption of hematoporphyrin onto polyalkyl cyanoacrylate nanoparticles: carrier

capacity and drug release. Int J Pharm 1991; 70: 129-135.

Gaspar R, Preat V, Roland M. Nanoparticles of polyisohexyl cyanoacrylate (PIHCA) as carriers of primaquine: formulation,

physico-chemical characterization and acute toxicity. Int J Pharm 1991; 68: 111-119.

Sommerfeld P, Scroeder U, Sabel BA. Long-term stability of PBCA nanoparticle suspensions suggests clinical usefulness.

Int J Pharm 1997; 155: 201-207.

Douglas SJ, Davis SS, Illum L. Biodistribution of poly(butyl 2-cyanoacrylate) nanoparticles in rabbits. Int J Pharm

; 34: 145-152.

Moghimi SM, Davis SS. Innovations in avoiding particles clearance from blood by kupfer cells: cause for reflection.

Crit. Rev. Ther. Drug Carrier Syst. 1994; 11: 31-59.

Parfitt K. Antineoplastics and immunosuppressants. In: Parfitt K, ed., Martindale, 32nd ed. Pharmaceutical press,

London, 1999: 529-531.

Bhawal S, Pokhriyal NK, Devi S. Translucent nanolatexes through emulsion polymerization of ethyl acrylate. European

Polymer Journal 2002; 38: 735-744.

Muller RH, Lherm C, Herbot J, Blunk T, Couvreur P. Alkyl cyanoacrylate drug carriers: I. Physicochemical characterization

of nanoparticles with different chain length. Int J Pharm 1992; 84: 1-11.

Hawley AE, Illum L, Davis SS. Lymph node localization of biodegradable nanospheres surface modified with poloxamer

and poloxamine block co-polymers. FEBS letters. 1997; 400: 319-323.

Takakura Y, Matsumoto S, Hashida M, Sezaki H. Enhanced lymphatic delivery of mitomycin C conjugated with

dextran. Cancer Res 1984; 44: 2505.

Douglas SJ, Illum L, Davis SS, Kreuter J. Particle size and size distribution of poly(butyl-2-cyanoacrylate) nanoparticles.

J Colloid Interface Sci, 1984; 101: 149-157.

Pain D, Das PK, Ghosh, PC, Bachhawat BK. Increased circulatory half-life of liposomes after conjugation with dextran.

J Biosci 1984; 6: 811-816.

Duncan R. Polymer conjugates for tumor targeting and intracytoplasmic delivery. The EPR effect as a common

gateway? Pharm Sci Tech Today 1999; 2: 441-449.

Vigevani A, Williamson MJ. Doxorubicin. In:Analytical profiles of drug substances. Florey K, ed., Academic press,

New York, 1980; 245-274.

Illum L, Khan MA, Mak E, Davis SS. Evaluation of carrier capacity and release characteristics for poly(butyl 2-

cyanoacrylate) nanoparticles. Int J Pharm 1986; 30: 17-28.

Horwitz BA, Shintizky M, Kreutz W, Yatwin MB. pH sensitive liposomes: possible clinical implications. Science

(Wash DC). 1980; 210: 1253-1255.

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Published

2004-06-16

How to Cite

1.
HARIVARDHAN-REDDY L, MURTHY R. Study of influence of polymerization factors on formation of poly(butyl cyanoacrylate) nanoparticles and in vitro drug release kinetics. Ars Pharm [Internet]. 2004 Jun. 16 [cited 2024 May 18];45(3):211-34. Available from: https://revistaseug.ugr.es/index.php/ars/article/view/5111

Issue

Vol. 45 No. 3 (2004)

Section

Original Articles

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