Controlled release studies of 5-Fluorouracil through poly (vinyl caprolactum-co-vinyl acetate) microspheres

B Yerriswamy, C Lakshmi Narayana Reddy, C Venkata Prasad, M C S Subha, K Chowdoji Rao, Venkatareddy G


Novel poly (vinyl caprolactam-co-vinyl acetate) microspheres were crosslinked with N’, N’ methylene bisacrylamide (NNMBA) prepared by free radical emulsion polymerization. This was done by using vinyl caprolactam, vinyl acetate,
and NNMBA with varying amounts. 5-Fluorouracil (5-FU) is an anticancer drug which was mixed into these microspheres during in situ polymerization. These microspheres were characterized by using differential scanning calorimetry (DSC),
X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. XRD and DSC results indicated that there was uniform distribution of 5-FU drug particles in microspheres, and SEM pictures suggest that the microspheres are in
spherical shape. Both encapsulation efficiency and release patterns are found to be dependent on the amount of crosslinking agent and amount of drug loaded. From the results of drug release kinetic studies, an anomalous and nonFickian behavior was observed in the present studies. Furthermore, in vitro release studies indicated the release of 5-FU up to 10 hours.

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Wu C, Zhou S, Au-yeung SC, Jiang S. Volume phase transition of spherical microgel: Particals. Angew Makramol Chem 1996:240:123-36.

Lowe TL, Tenhu H. Interactions of thermally responsive polyelectrolyte

lattices with low molar mass organic molecules studied by light

scattering. Macromolecules 1998;31:1590-4.

Lowe TL, Benhaddaou M, Tenhu H. Partially fluorinated thermally

responsive lattices of linear and crosslinked copolymer. Polym Sci B

Polym Phys 1998;36:2141-52.

Eisele M, Byrchard W. Hydrophobic water-soluble polymers dilute

solutions properties of poly (1-vinyl-2-piperidone) and poly (N-vinyl

caprolactam). Macromol Chem Physic 1990;191:169..

Makhaeva E, Thanh LT, Starodoubtsev SG, Khokhlov AR. Thermo

shrinking behavior of poly(N-vinyl caprolactam) gels in aqueous

solution. Macromol Chem Physic 1996;197:1973-82.

Gao Y, Au-yenung SC, Wu C. Interaction between Surfactant and Poly

(N-vinyl caprolactam) Microgels. Macromolécules 1999;32:3674-7.

Lau AC, Wu C. Thermally Sensitive and Biocompatible Poly (N-vinyl

caprolactam): Synthesis and characterization of high molar mass linear

chains. Macromolecules 1999;32:581-4.

Galaev IY, Mattiasson B. Smart polymers and what they could do in

biotechnology and medicine. Trends Biotechnol 1999;17:335-40.

Laukkaen A, Hietala S, Maunu SL, Tenhu H. Poly(N-vinyl caprolactam)

Microgel particles grafted with amphiphilic chains. Macromolecule


Goddsrd ED, Guber JV. Principles of polymer science and technology in

cosmetics and personal care. New York: Marcel Dekker; 1999. p. 217-74.

Pong S, Wu C. Poly (N-vinyl caprolactam) microgels and its related

composites. Macromol Symp 2000:159:179-86.

Makvicheva EA, Tkacuk NE, kuptsova SV, Dugina TN, Strukova SM, Krish YE, et al. Immobilized enzymes and cells in poly(N -vinyl caprolactam)- based hydrogels. Appl Bioche Biotechnol 1996;88:1-3.

Vihola H, Laukkanen A, Hirvonen J, Tenhu H. Binding and release

of drugs into and from thermosenesitive poly (N-vinyl caprolactam)

nanoparticless Eur J Pharm Sci 2002;16:69-74.

Kirsh YE. Water-soluble poly (n-vinylamides). Chichester: Wiley; 1998.

Matsuyama H, Teramoto M, Urano H. Analysis of solute diffusion in

poly(vinyl alcohol) hydrogel membrane J Memb Sci 1997;126:151-60.

Heidelberger C. Cancer medicine. 2nd ed. Philadelphia: Lea and Febiger;1961;801.

Waxman S, Scanlon KJ, Greenspan EM. Clinical interpretation and

practice in chemotheraphy. New York: Raven Press; 1982. p. 38.

Sommadossi P, Gewirtz DA, Diasio RB, Aubert C, Cano JP, Goldman ID.

Rapid catabolism of 5-fluorouracil in freshly isolated rat hepatocytes

as analyzed by high performance liquid chromatography. J Biol Chem


Einmhl S, Zigani M, Varesio E, Heller J, Veuthey JL, Gurny R. Concomitant and controlled release of dexamethasone and 5-fluorouracil from poly(orthoester). Int J Pharm 1999;189:185-98.

Babu VR, Sairam M, Hosamani KM, Aminabhavi TM. Development of

-fluorouracil loaded poly (a crylamide-co-methylmethacrylate) novel

core-shell microspheres: In vitro release studies.Int J Pharm 2006;325:


Denizli A, Kiremitçi M, Piskin E. Subcutaneous polymeric matrix

system poly (HEMA-BGA) for controlled release of an anticancer drug

(5-fluorouracil): I. Synthesis and structure, Biomaterials 1988;9: 257-62.

Kurkuri MD, Aminabhavi TM. Poly (vinyl alcohol) and poly (acrylic acid)

sequential interpenetrating network pH-sensitive microspheres for

the delivery of diclofenac sodium to the intestine. J Control Release


Ritger PL, Peppas NA. A simple equation for description of solute releaseI. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release 1987;5:23-6.

Reddy MK, Babu VR, Krishna Rao K, Subha MC, Rao CK, Sairam M, et al.Temperature sensitive semi-IPN microspheres from sodium alginate and

N-isopropylacrylamide for controlled release of 5-fluorouracil. J Appl

Polym Sci Symp 2007;107:2820-9.

Vihola H, Laukkanen A, Tenhu H, Hirvonen J. Drug release characteristics of physically cross-linked thermo sensitive poly(N-vinylcaprolactam) hydrogel particles. J Pharm Sci 2008;97:4783-93.

Krishna Rao K, Kiran Kumar A, Rao MK, Subha MC. Yong-Ill Lee Semi-IPN hydrogels based on Poly (vinyl alcohol) for controlled release studies of chemotherapeutic agent and their Swelling characteristics. Polym Bull 2008;61:81-90.

Prabaharn M, Grailer JJ, Steeber DA, Gong S. Stimuli responsive chitosan- graft-poly (N-vinyl caprolactam) as promising material for controlled hydrophobic drug delivery. Macromol Biosci 2008;8:843-51.



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