Tetracycline diffusion through bacterial cellulose--polyvinyl alcohol membranes.

Stoica, Anicuta ; Stroescu, Marta ; Chiciudean, Teodor Gelu 等

Abstract: An experimental study concerning tetracycline diffusion through bacterial cellulose-polyvinyl alcohol membranes has been performed and it is described in the present paper. The mentioned membranes can be used as transdermal systems for antibiotics controlled release. This could be an interesting application for bacterial cellulose, which is also used as artificial skins and as wound dressing. Key words: bacterial cellulose, polyvinyl alcohol, diffusion, tetracycline.

1. INTRODUCTION

Bacterial cellulose (BC) produced by Acetobacter xylinum has the same composition but has unique properties compared with cellulose from plants and can be considered superior on many accounts. For instance, BC microfibrils have a density of 1600 kg/[m.sup.3], a Young's modulus of 138 GPa, and tensile strength of at least 2 GPa, properties almost equal to those of aramid fibers. BC possesses higher water holding capacity, higher crystallinity, and higher tensile strength. In comparison with other microbial polymers, it is produced in relatively larger quantities. By controlling the physiological conditions of bacterial growth, morphologically reproducible pellicles or fibrils can be obtained, which can be easily processed into membranes of BC or composites with different materials. This biopolymer has several practical applications. Its use varies from serving as food all the way to acoustic diaphragms and to obtaining electronic paper (Shah and Brown, 2005). Bacterial cellulose membranes have been utilized for pervaporation studies (Pandey et al., 2005) and in combination with palladium they are being used to produce experimental fuel cells for generating electricity (Evans et al., 2003).

BC also has numerous medical applications, such as wound dressings, artificial skins, cartilages and artificial blood vessels (Czaja et al., 2006; Wan et al., 2006). Bacterial cellulose can be used in composite materials with xyloglucan or pectin (Astley et al., 2003), with lignosulfonate (Keshk, 2006; Keshk and Sameshima, 2006), with chitosan (Ciechanska, 2004), cellulose acetate butyrate (Gindl and Keckes, 2004), hydroxyapatite (Hung et al., 2006; Hutchens et al., 2006) and with polyvinyl alcohol especially for biomedical purposes. Bacterial cellulose was also used to obtain a composite membrane for transdermal delivery of S-propranolol enantiomer based on the controlled pore functionalization of bacterial cellulose membranes using a molecularly imprinted polymer (MIP) layer synthesis (Bodhibukkana at al., 2006).

The aim of this paper is to present experimental results obtained from bacterial cellulose polyvinyl alcohol composite membranes containing tetracycline clorhydrated as a model drug for transdermal controlled released applications.

2. EXPERIMENTAL DEVELOPMENTS

Several different techniques for bacterial cellulose production have been reported. The choice of a cultivation technique is strictly dependent on further biopolymer commercial destination. In this work, for obtaining BC microfibrils, an air lift reactor with 1.5 l capacity has been used. The culture medium used herein was a modified Hestrin & Schramn (MHS) medium.

After 7 days, the microfibrils obtained were purified by boiling in a 0.5 M aqueous solution of NaOH for 30 minutes. The BC microfibrils were then washed with deionized water several times until the pH of water became neutral. To prepare composite membranes, BC microfibrils and polyvinyl alcohol (PVA) 4% aqueous solution were very well mixed and then rolled into sheets. In order to test these membranes as transdermal tetracycline delivery system, an aqueous solution of tetracycline was also mixed with BC and polyvinyl alcohol. The obtained membranes were tested in a diffusion cell in order to determine diffusion coefficients of tetracycline from composite membranes into water. The cell had one very well agitated compartment that would eliminate liquid boundary layers resistance. The diffusion cell was maintained at room temperature (25[degrees]C). Tetracycline concentration was measured at 365 nm using an UV-VIS spectrophotometer CINTRA 6 CBS-Scientific (Australia).

[FIGURE 1 OMITTED]

3. RESULTS AND DISCUSSION

Several membranes with different thicknesses have been tested. Figure 2 presents experimental results obtained for two composite membranes with different thicknesses.

In order to determine tetracycline diffusion coefficients through bacterial cellulose membranes, the following mathematical model has been used. This model assumes that the liquid is perfectly mixed (assumption which is valid for high agitator rate in the experimental cell compartment). The drug transport is done convectively from the membrane to the aqueous phase in the receptor compartment. Within the membrane, transport is diffusive. Local balance is kept between external phases and the membrane itself.

[partial derivative][C.sub.m]/[partial derivative]t = [D.sub.m] [[partial derivative].sup.2][C.sub.m]/[partial derivative][x.sup.2] (1)

In the bulk phase, the balance equation is:

[V.sub.1] d[C.sub.1] / dt = [k.sub.1]S([C.sub.1] - [C.sub.m] / K) (2)

Initial and boundary conditions are as follows:

I.C. t = 0, [C.sub.1,0] = 0,t = 0, 0 [less than or equal to] X, [C.sub.m] = [C.sub.m0] (3)

B.C. t [greater than or equal to] 0, x = [delta], [D.sub.m] [partial derivative][C.sub.m]/[partial derivative]x = - [k.sub.1]([C.sub.1] - [C.sub.m]/K) (4)

t [greater than or equal to] 0, x = 0, [partial derivative][C.sub.m]/[partial derivative]x = 0 (5)

The basic differential equations of the model were solved numerically, by means of finite difference method.

In order to obtain tetracycline diffusion coefficient values through BC/PVA composite membranes, the model prediction was examined in relation to the experimental data. The parameters used in our modeling approach are as follows: distribution coefficient (K), mass transfer coefficient k1 and diffusion coefficient [D.sub.m]. Only two parameters [D.sub.m] and K were identified by fitting experimental data with theoretical results. The mass transfer coefficients were estimated based on liquid flow in the diffusion cell. Figure 3 shows the comparison between experimental data and theoretical prediction for BCPVA composite membranes. A very good agreement between experimental and theoretical data has been obtained as it can be easily observed in the chart.

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

For tetracycline diffusion through BC-PVA composite membranes, a diffusion coefficient [D.sub.m]=[1.10.sup.-13] [m.sup.2]/s was found. The identified values of tetracycline interphase distribution coefficient (K=75) show that the membranes slowly release this drug.

4. CONCLUSIONS

Biocellulose fibrils obtained in an air lift reactor have been used to make composite membranes with polyvinyl alcohol in order to simulate a transdermal delivery system for antibiotic release. The membranes containing also tetracycline as the model drug have been tested in a diffusion cell. A simple diffusion model was proposed to clarify the experimental results. The value of the diffusion coefficient was obtained by fitting experimental data with theoretical results.

5. REFERENCES

Astley, O. M., Chanliaud, E., Donald, A. M, Gidley, M. J., Journal of Biological Macromolecules (2003), 32, 28-35

Bodhibukkana, C., Srichana, T., Kaewnopparat, S., Tangthong, N., Bouking, P., Martin, P. G., Suedee, R.., J. Control Release (2006), 113 (1), 43-56

Ciechanska, D., Fibres & Textiles in Eastern Europe (2004), 12, No. 4(48), 69-72

Czaja, W., Krystynowicz A., Bielecki, S., Brown Jr. R. M., Biomaterials (2006), 27, 145-151

Evans B. R., O_Neill H. M., Malyvanh V.P., Lee I, Woodward J., Biosens. Bioelectron. (2003), 18, 917-923

Gindl W., Keckes J., Composites Science and Technology (2004), 64, 2407-2413.

Hong L., Wang Y.L., Jia S.R., Huang Y., Gao C., Wan Y.Z., Materials Letters (2006), 60, 1710-1713

Hutchens S. A., Benson R. S., Evans B. R., O'Neill H. M., Rawn C. J., Biomaterials (2006), 27, 4661-4670.

Keshk S., Sameshima K., Enzyme and Microbial Technology (2006), 40, 4-8.

Keshk, S., Enzyme and Microbial Technology (2006), 40, 9-12

Pandey, L. K., Saxena, C., Dubey, V. (2005), Separation and Purification Technology, 42, 213-218

Shah, J., Brown Jr., R. M., Appl. Microbial. Biotechnol. (2005), 66, 352-355.

Wan, Y.Z., Hong, L., Jia, S.R., Huang, Y., Zhu, Y., Wang, Y.L., Jiang, H.J., Composites Science and Technology (2006), in press, doi:10.1016/j.compscitech.2005.11.027