Effect of porous silica on sustained release behaviors of pH sensitive Pluronic F127/poly(acrylic acid) hydrogels containing tulobuterol

doi:10.1016/j.colsurfb.2010.06.017

Colloids and Surfaces B: Biointerfaces

Volume 80, Issue 2, 15 October 2010, Pages 240-246

https://doi.org/10.1016/j.colsurfb.2010.06.017 Get rights and content

Abstract

pH sensitive Pluronic F127 (PF127)/poly(acrylic acid) (PAAc) hydrogels containing tulobuterol-loaded silica were prepared with PF127 content. The effects of the PF127 content and silica on the sustained release behaviors of the PAAc hydrogels were investigated. The results showed that the swelling ratio and rate of the hydrogels were decreased with increasing PF127 content compared with pure PAAc hydrogel, whereas the stability of the hydrogels was enhanced by the addition of PF127 after swelling. The release behaviors of the PAAc hydrogels showed that the release rate of the pure PAAc hydrogels increased as the pH value of the release medium was increased, whereas it decreased with the addition of PF127 due to a decrease in the swelling rate. Also, the hydrogels containing tulobuterol-loaded silica showed more sustained release behaviors, which was attributed to the delayed diffusion rate of the drugs by physical interaction between the drugs and porous silica.

Introduction

Controlled drug delivery systems (CDDS), that is, systems that release a drug with a controlled profile so as to maintain an appropriate concentration for desired periods of time, are of great interest in the pharmaceutical industry. CDDS have many advantages and provide more effective therapy through elimination of both under- and overdosing, reducing indosing frequency, improved patient compliance, localized drug delivery, drug protection against degradation in the body, and reduced side effects. In addition, external stimuli controlled release systems offer many distinctive advantages compared with classical methods of drug delivery [1], [2], [3].

Recently, pH sensitive hydrogels have drawn considerable attention because of their potential applications in controlled release systems. Typical polymers such as poly(acrylic acid) (PAAc), poly(methacrylic acid), alginate, carboxymethyl cellulose, and hydroxypropyl methylcellulose have been studied as drug carriers [4], [5], [6], [7]. Among these, PAAc shows potential as a drug carrier with strong external stimuli sensitivity, such as temperature, electro-magnetic field, and pH condition as well as biocompatibility. However, it has limitations stemming from high swelling and dissolution in high pH solutions, leading to fast drug release from the PAAc matrix. Nevertheless, PAAc has many potential applications and it has been studied as artificial muscle as well as a drug carrier [8], [9], [10].

The high solubility of PAAc has conventionally been addressed by crosslinking it via chemical bonding. This provides a three-dimensional network of PAAc, thereby enhancing its mechanical properties and sustained release behaviors [11], [12], [13]. A notable chemical crosslinking method involves the use of copolymers or inter-polymer complexes. The incorporation of other polymers into the PAAc matrix leads to strong intermolecular interactions, such as hydrogen bonding, resulting in a polymer complex. The polymer complex can provide new physico-chemical characteristics by a synergistic effect of each polymer. Researchers have studied polymer complexes of PAAc with poly(ethylene glycol), polyvinyl alcohol, and polypyrrolidone. The resulting polymer complex method offers control over the various characteristics of the polymer complex, such as swelling and external sensitivity, leading to control of drug release behaviors. This is attributed to physical interaction between the carboxyl group of PAAc and the functional groups of other polymers [14], [15], [16].

Recently, polymer/nano-sized filler composites hydrogels have attracted considerable attention, because the incorporated nano fillers can provide enhanced physicochemical properties, such as mechanical and thermal properties of the hydrogels, and greater potential to control the drug release behaviors compared to pure polymers [17], [18].

Therefore, in this work, pH sensitive and insoluble poly(acrylic acid) (PAAc) hydrogels are prepared with mixing of Pluronic F127 (PF127). Tulobuterol is used as a model drug. The effect of PF127 on the 3D network structure and swelling of PAAc hydrogels is investigated as a function of PF127 content. In addition, the effect of porous silica on the sustained release behaviors of the PF127/PAAc hydrogels is also discussed.

Section snippets

Materials

Acrylic acid (AAc) and Pluronic F127 (PF127) were purchased from Aldrich. N,N′-methylene bisacrylamide (MBA) and ammonium persulfate (APS), used as a crosslinking agent and an initiator, were supplied from Aldrich. Glyceride fatty acids (GELUCIRE 44/14), used as solubilizer, were supplied from MaSung (Korea). As a model drug, tulobuterol base was supplied by Deabong LS (Korea). Silica (AEROSIL 200VV Pharma; specific surface area: 200 ± 25 m²/g, tapped density: 120 g/l) was supplied from Evonic. All

Characterization of PAAc/PF127 hydrogels

Fig. 1 shows the FT-IR spectra of pure PAAc, PF127, tulobuterol, and PF127/PAAc hydrogels. From the FT-IR spectra, in the case of PAAc, the strong absorption around 3400 cm⁻¹ and the peak at 2924 cm⁻¹ are attributed to OH and CH₂ groups, respectively. The asymmetrical and symmetrical –COO⁻ vibrations of PAAc in carboxylate form are respectively in a range of 1564–1539 and 1408–1419 cm⁻¹. PF127 shows a carbonyl band at 1734 cm⁻¹ and an aliphatic CH stretching band at 2881 cm⁻¹ [19], [20]. Tulobuterol

Conclusions

In this work, pH sensitive PF127/PAAc hydrogels containing tulobuterol-loaded silica were prepared and the effects of PF127 content and silica on the sustained release behaviors of PAAc hydrogels were investigated. It was found that these hydrogels showed pH sensitivity for the drug release. Furthermore, the addition of PF127 to PAAc can control the drug release behaviors as well as the degree of crosslinking of the hydrogels. The use of drug-loaded silica could further control the drug release

Acknowledgement

This work was supported by Inha University Research Grant.

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Effect of porous silica on sustained release behaviors of pH sensitive Pluronic F127/poly(acrylic acid) hydrogels containing tulobuterol

Abstract

Introduction

Section snippets

Materials

Characterization of PAAc/PF127 hydrogels

Conclusions

Acknowledgement

J. Control. Release

Adv. Drug Deliv. Rev.

Int. J. Pharm.

Adv. Drug Deliv. Rev.

Nucl. Instrum. Methods Phys. Res. Sect. B

Eur. J. Pharm. Biopharm.

Int. J. Pharm.

Biomaterials

Carbohydr. Polym.

Int. J. Pharm.

Polymer

J. Control. Release