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The 4th IEEE International Conference on E-Health and Bioengineering - EHB 2013

Grigo re T Po pa University o{Medicine and Pharmacy, ia:ji, Ro mania, November 21-23,2013

Use of Bacterial Cellulose-Glycerol-Poly(vinyl
alcohol) Composites in Drug Release
Ramona-Daniela Pavaloiu, Tanase Dobre
Faculty of Applied Chemistry and Material Science
University Politehnica of Bucharest
Bucharest, Romania
pavaloiu_daniella@yahoo.com

Cristina Hlevca
National Institute For Chemical-Pharmaceutical Research and
Development - ICCF Bucharest
Bucharest, Romania

Abstract- Bacterial cellulose (BC) is a biomaterial suited for

elastic modulus. Also, it has a high surface area per unit mass,
feature combined with its highly hydrophilic nature, confers a
high liquid loading capacity [1].
The above listed properties make BC an attractive
biomaterial as scaffold material for tissue regeneration or
replacement, wound dressings, artificial skin, film coating
agent and matrix for drug loading and drug release [2-5].
A method to improve further more the remarkable features
of BC is through combination of bacterial cellulose with other
polymers (poly(vinyl alcohol) [6], poly(ethylene glycol) [7],
alginate [8], starch [9, 10], chitosan [11, 12]) or with
inorganic materials (hydroxyapatite [13]).
Several preparation methods of BC based composites were
reported: direct addition of polymer into BC culture medium
[14], mixing BC powder or BC ground with polymer solution
[15] and impregnation method by immersing BC membranes
in polymer solution [7]. Although, in present, there are a
considerable number of articles about the preparation and
characterization of various BC composites for biomedical
applications, only a small number of papers related to drug
delivery have been published [16,17].
The aim of this paper was to investigate the use of BC
composites for drug release. In this purpose multilayer
composites BC-Glycerol- Poly(vinyl alcohol) were prepared
and in vitro drug release studies were performed to evaluate
their overall potential in drug delivery applications.
Poly(vinyl alcohol) (PVA) materials present also desirable
characteristics for drug delivery applications, such as: high
degree of swelling, simple chemical structure, elastic nature,
non-toxic, non-carcinogenic, and bio-adhesive properties.
Amoxicillin, an antibiotic with high solubility in water (3.4
mg/mL) and commonly used against a broad-spectrum of
Gram-positive and Gram-negative microorganisms, was
chosen as model drug.
To our best knowledge, this is the first time that a
multilayer composite system based on BC-Glycerol and PVA
prepared in this manner was investigated for drug release
studies.

various biomedical applications, due to its unique nanostructure,
that confers remarkable physical and chemical properties, such as:
excellent elasticity, biocompatibility, high purity, high tensile
strength and high elastic modulus. The article describes the
mechanism and amoxicillin release profiles from bacterial
cellulose-glycerol-poly(vinyl alcohol) composites, in the aim to use
such systems in controlled drug delivery field. Obtained data from
these composites were slightly smaller than Be-Glycerol, probably
due to the fact that PVA layers provide an additional barrier for
drug release. The presented data are of interest for the
biomaterials community.
Keywords- bacterial cellulose, drug release, biomaterial.

I.

INTRODUCTION

The use of biopolymers in biomedical applications has
gained an increased interest due to their renewable nature,
biocompatibility and biodegradability. As example,
biopolymers like cellulose, starch, chitosan, alginate,
carrageenan, hyaluronic acid were investigated for
biomedical and pharmaceutical field. These biopolymers are
available, biodegradable, biocompatible, have low level of
toxicity and can be chemical modified; all properties listed
above are relevant for drug delivery applications. Although a
considerable palette of products based on conventional
biopolymers has been research and developed, there is still
the need to discover and explore new materials that can be
used to design drug-delivery systems.
A biopolymer with great potential is bacterial cellulose or
biocellulose (Be), also known as microbial cellulose. BC is a
polysaccharide synthesized by various species of bacteria,
such
as
Aerobacter,
Acetobacter,
Achromobacter,
Agrobacterium, Alacaligenes, Azo to bacter, Rhizobium and
Sarcina. It is chemically identical to plant cellulose, but with
a significantly different fibrous nanostructure.
Due to its unique structure, BC possesses superior physical
and chemical properties compared to plant cellulose. BC has
excellent elasticity, biocompatibility, high purity, and good
mechanical properties, including high tensile strength and

978-1-4799-2373-1/13/$31.00 ©2013 IEEE

5 A3 0.5 4 B2 1.0 0. Obtained data suggest that these composites could be exploited in controlled delivery field and the amount of drug released could be adjusted by varying glycerol and emulsifier concentrations and also by adding PVA layers. soaked in 25 mL of an aqueous buffer solution (pH 7. HexadecyItrimethy[ ammonium bromide (CTABr. according to the standard amoxicillin calibration curve.0 0. HO TABLE I EXPERIMENTAL PART -oJY.5 mg/mL).5 0. glycerol and emulsifier) were soluble in this medium. This research continues the investigation of BC based composite for drug release. The incorporation of drug. a BC-Glycerol membrane was placed above it. and the other half were used further for multilayer composite preparation.75 A4 1.5 A2 1.75 4 III.4) of different compositions (listed in Table I) and slightly shaken for 2 h. drained at 50% humidity.5 4 B3 0. Obtained data proved that release was influenced by drug concentration. B. A3 and A4). . A2.5 0. and then another PYA layer was poured. designing new multilayer composites starting from BC-Glycerol composites membranes prepared in the same manner used in our previous experiments. where Mt is the cumulative amount of amoxicillin released from composites at time t. Glycerol was used as a plasticizer due to the fact it increases low malleability and as well as the swelling (water holding and retention) of dry BC membranes.5 0. G[ycero[. After drug adsorption. and Moo is the cumulative amount of amoxicillin released from composites at infinite time. The prepared composites were allowed to dry at room temperature. in static culture using a modified HS medium containing fructose (2%). 1. BC membranes (99% water content) were produced in the Microbiology Laboratory of Chemical Engineering Department (UPB). The multilayer composites were prepared by placing dried BC-Glycerol membrane between two PVA layers.5 0. the BC membranes were dried at room temperature. C.75 Bl 0. All chemicals and reagents used were of analytical grades. Preparation oiBC-Glycerol Membranes Bacterial cellulose (BC) membranes were obtained from Acetobacter sp.4 was chosen as drug release medium because simulates the condition of intestinal fluid. B3 and B4). All release studies were performed in duplicate. Half of these prepared membranes were used in drug release study (A [. interaction term between drug concentration and glycerol concentration and interaction term between glycerol concentration and an emulsifier concentration [18]. The chemical formula of amoxicillin. Aqueous buffer pH 7. = A. The solution was kept under stirring until was cooled down to room temperature to prevent polymer agglomeration. chemical formula: CI9H4zNBr). B2. All the substances used (drug. Preparation ofBC-Glycerol-PVA Composite PVA solution was prepared by dissolving PVA in distilled water at 90°C (4%). The drug concentration was kept constant for all samples (1. composites were removed from the cast plate and used in drug release study (B1. due to the fact that PYA layers confer an additional barrier for drug release. A multilayer composite was prepared as follows: a PVA layer was poured in a plate. Materials Amoxicillin. After drying. Drug release study In vitro drug release profiles were obtained by immersing composites into 25 mL buffer solution until maximum release is achieved. glycerol concentration. Amoxicillin release values of BC-Glycerol-PVA multilayer composites and BC-Glycerol composites were present in Fig.0 0. PYA % RESULTS In previous studies the release of amoxicillin from BC­ Glycerol composites membranes was investigated using a Box Behnken Design as statistical tool. The results were presented in terms of the ratio MtlMoo as a function of time. Because of the hydrophilic nature of both BC and PVA. It was observed that values obtained from BC-Glycerol­ PVA multilayer composites were slightly smaller than BC­ Glycerol. A.75 4 B4 1. the amount of drug released was determined at 229 nm wavelength using an UV-V[S spectrophotometer C[NTRA 6 (GBS-Australia). Wet BC membranes were weighted.)=t'x }o Fig. glycerol and enhancer into BC membranes was performed after removing approximately a half of BC water content to assure total absorption. 2.[I. in order to obtain modified drug release rates. it is expected a strong interaction between them. OH SAMPLE COMPOSITION Composition --- Sample name Glycerol % CTABr mM Al 0. PVA (average Mr 145000 Da. The samples were kept at room temperature (25°C) and slightly shaken.0 0. At predetermined moments. 99 mole % hydrolyzed) were purchased from Sigma Aldrich.

1�0.93 0. For n < 0.28 6.22 12.65 0. According to the obtained value of diffusion exponent n the release mechanism can be elucidated.2 7.47 1.6 O.94 B2 0. A4). -----.9 A2 -Linear(A2) -0.2 0.1 + + + • • _A1 2000 -0.3 + Model parameters +- + • PARAMETERS OF POWER LAW MODEL • • L- 0.6- .8 g ?i • 1=- 0. � Diflusion exponent . 3. (Fig.7 0.5 this indicates that Fickian diffusion is the dominating process.5 A I • A4 -Linear(A4) .9 _A4 _84 0. release conforms to an anomalous diffusion (non-Fickian diffusion) and for n < 1 the drug is released in later stages.5 ::E 0.4 log (t) Fig.3 0.08 0. parameter with strong influence upon drug release from Be-Glycerol membranes. the values of diffusion exponent n and model constant k were calculated. 2. B4) and BC-Glycerol composites (AI.. � Cl .8 • -0.6 0.96 Bl Model constant Correlation coefficient 0.1 o.7 -0.4 -0. the power law model was applied to the experimental data. . k values and regression coefficients are represented in Table II.6 4000 6000 time(s) 8.03 0.94 B4 0.6- B1 -Linear(B1) + B2 -Linear(B2) B3 -0.8 A1 -Linear(A1) -0.8 Linear(B3) A -1 B4 -Linear(B4) -1.45 0.2 -1.2 0. according to the literature [19].95 In order to determine the mechanism of the release process.Q 7.5 < n < 1.95 0.01 rl--- _0. 7. Most of the samples have diffusion exponent value n smaller than 0. 2000 6000 4000 time(s) 8000 1�• 0. (1) Where k is a constant depending on the macromolecular network characteristics of the composite and n is the diffusion exponent indicating release kinetic mechanism. 3) The n.2 '8 :.8 g ?i 0. for 0.1 Sample name .5 with release dominated by non­ Fickian process.93).98 B3 0. � Cl . A4 and B4 have n values higher than 0.6- -1 log (t) 714 -0. Samples A3. A possible explanation is the fact that interaction term between glycerol concentration and emulsifier concentration has high value.48 0.33 0.65 0.6 n k'102 R2 Al A2 A3 A4 0.89 1.7 TABLE II • + 0.S ::E 0. drug release follows Fickian diffusion. Variation of log (Mf/Moo) with log(t) for BC-Glycerol-PVA multilayer composites (BI-B4) and BC-Glycerol composites (AI-A4).56 4.37 0.Q -0.99 0. Fractional release of amoxicillin from BC-Glycerol-PVA multilayer composites (Bl.4 -0.4 0.9 • 0. By plotting log (MtIMoo) against log (t).63 0.. MtlMoo =kt.71 0. It can be observed a good agreement between the experimental data and the power law model (correlation coefficient R2>0. this model can be expressed as: Fig.2 '8 :.6 -0.6 -----.4 [ • + 1 A3 Linear(A3) -0.4 0. .8 8000 8.3 7. as the slopes and as the intercept of the straight lines fitted to the data.15 0.5..

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