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Preparation and characterization of pH-sensitive microparticles based on polyelectrolyte complexes for antibiotic delivery.

INTRODUCTION

The idea to design new pharmaceutical formulations for drug delivery system is directed to obtain better control of residence time and concentration of the drug in the damaged organ or tissue. The development of a safe and efficient polymer-based drug carrier system is necessary in order to achieve an optimal therapy, especially in cancer treatment which involves the use of aggressive drugs with a low therapeutic index [ l -4]. Polyelectrolyte complexes have been explored for their potential in colon-specific drug delivery systems due to their ease preparation, avoidance of hazardous procedures, possibility to fabricate a variety of combined structures, and low cost [5-8]. Moreover, investigation on polyelectrolytes received renewed attention in the designing of drug delivery systems and scaffolds for tissue engineering applications since they offer the possibility to combine physicochemical properties of at least two electrolytes and their similarities to some body fluids under physiological conditions [9, 10].

In addition, when the oral route administration is selected for treatment of inflammatory bowel disease (IBD), the drug should pass through different biological fluids. Thereby, for successful colon targeted drug delivery, a drug needs to be protected from release and degradation in the stomach and then to be released in a controlled manner in the small intestine [11-15]. Bearing that in mind, in this study poly(acryloxyethyl-trimethylammonium chloride-co-N-vinyl-2-pyrrolidone) was synthesized as a new synthetic copolymer and then combined with sodium alginate (AlgNa) to form pH-sensitive microparticles. With this combination we wished exploit the possibility to mix attractive properties of natural and synthetic macromolecules leading stable and desired architecture with potential application as biomaterials.

Alginate is a water-soluble anionic polysaccharide extracted from brown seaweed and one of the most common materials used to form polyelectrolyte complexes in drug delivery systems. Due to their abundance in nature, biocompatibility and biodegradability it has been widely used as matrix for entrapment of bioactive agents and cells [16-21]. Furthermore, the interaction between alginate and other polymers to produce microparticles continues to receive much attention in pharmaceutical applications since the oral route remains the most preferred. For example, chitosan-reinforced alginate microparticles containing different kind of drug for oral delivery have been reported by several researchers [22-24]. Recently, Lim et al. [25] developed core-shell structured alginate-PLGA/PLLA microparticles to encapsulate water soluble drugs. It was showed that incoiporation of alginate in these synthetic polymers produced increase encapsulation efficiency of metoclopramide. Also in an original article, Finotelli et al. [26] developed alginate/chitosan microparticles containing magnetic nanoparticles in order to obtain an insulin delivery system by application of oscillating magnetic field.

Acryloxyethyl-trimethylammonium chloride (Q) was the cationic monomer selected to prepare synthetic copolymer due to the presence of ammonium quaternary group which allows good hydrophilicity for aqueous applications with multiples points of interactions [27], Polymers containing this group have several advantages, including environment stability, low toxicity, lack of skin irritation and excellent cell membrane penetration properties [28, 29], Complementarily the incorporation of N-vinyl-2-pyrrolidone (VP) units is motivated by the idea of providing more stability to the system, considering that the amphiphilic character of VP provides excellent route for the preparation of materials with adequate hydrophilic/hydrophobic balances. Moreover, VP has been chosen as comonomer in the production of copolymers used in biomedical applications due to the good biocompatibility and non-immunogenetic properties of its homopolymer (approved by the United States Food and Drug Administration, U.S. FDA) [30, 31J. Homopolymer and copolymer of N-vinyl-2-pyrrolidone have been used as an antimicrobial agent in clinical practice and also as the main component of temporary skin covers [32, 33].

On the other hand, the use of microparticles loaded with antibiotics would be beneficial for intestinal infections, ulcerative colitis and carcinomas [34, 35]. Thereby poli(Q-co-VP)/AlgNa microparticles have been evaluated as a pH-sensitive system for controlled delivery of antibiotic. Antibiotic are prescribed for the treatment of various bacterial infections and Cephalosporin has been employed in this direction for more than two decades. Cefotaxime belongs to the third generation of Cephalosporin and we considered it as a drug model because of its wide-spectrum of antimicrobial activity and its excellent water solubility [36]. Additionally this antibiotic is an alternative to patient allergic to penicillin or aminoglycosides. The use of polymer-based microparticles has been reported by several authors for the successful encapsulation of variety of antimicrobial agents. Singh et al. [37] have reported tetracycline hydrochloride release from psyllium 2-hydroxylethylmethacrylate and acrylamide-based polymer networks for use in colon drug delivery. Vasiliu et al. [38] studied the release process of chloramphenicol succinate sodium salt and Cefotaxime sodium salt from polyelectrolyte complex microparticles.

In this research, hydrophilic and pH-sensitive poly(Q-co-VP)/AlgNa microparticles were developed to encapsulate and release an antibacterial agent which is efficient in the treatment of inflammatory bowel diseases. For this purpose, synthetic copolymers with high content of positive charge were prepared and their interaction with sodium alginate was followed conductimetrically. The lyophilized microparticles obtained were evaluated based on particle size, morphology and the Cefotaxime release in different pH conditions (pH 1.2; 4.5; and 6.8).

EXPERIMENTAL

Materials

Acryloxyethyl-trimethylammonium chloride (Q, Sigma Aldrich), potassium persulfate ([K.sub.2][S.sub.2][O.sub.8], Fluka), acetone (Merck), and calcium chloride anhydrous (Ca[Cl.sub.2], BDH) were used as received. A-vinyl-2-pyrrolidone (VP, Sigma Aldrich) was distilled under vacuum before use: 55[degrees]C/14 mm Hg. Sodium alginate was purchased from SIGMA Chemical. It was carefully purified prior to use. Its viscosity average molar mass was 3.83 X [10.sup.4] g/mol; which was determined by viscosimetry in 0.2 M NaCl at 25[degrees]C. Cefotaxime sodium salt was purchased from Pharmaceutical Laboratory of Cuba (IMEFA).

Copolymerization Reaction

Different compositions of poly(Q-co-VP) was prepared by radical polymerization in aqueous solution, varying molar ratio of monomers in the presence of [K.sub.2][S.sub.2][O.sub.8] (0.05 g, 1% with respect to monomer) as initiator. The reaction mixture was transferred to a three neck flask and deoxygenated by bubbling with nitrogen for at least 30 min. Afterward the polymerization was initiated by adding the initiator. The reaction was kept at 60[degrees]C under a [N.sub.2] atmosphere and stirring was maintained for 6 h. The polymer was isolated from the reaction medium by acetone precipitation, purified in triplicate and then lyophilized. Conversions were determinate gravimetrically after exhaustive drying of the isolated copolymer sample.

Conductimetric Measurements and Copolymer Composition

The molar fractions of acryloxyethyl-trimethylammonium-chloride monomer units incorporated in the copolymers were determined by potentiometric titrations. Conductimetric experiments were carried out in glass cell at 25[degrees]C [+ or -] 1[degrees]C employing a Digital CR1NSON equipment. The experiments were always performed in aqueous solutions containing sodium alginate (5 X [10.sup.-4] mol/L) and poly(Q-co-VP) (5 x [10.sup.-3] mol/L) in deionized water under magnetic stirring. The pH-values of the polyelectrolyte solutions were those of the starting solutions. A silver electrode was used as analytic sensor.

FTIR Analysis

The identification of functional groups present in the copolymers and the confirmation of presence of the drug in the microparticles were done by Fourier Transformed Infrared spectroscopy (FTIR) in an Excalibur Varian 3100 spectrometer. Samples spectra were obtained using attenuated total reflectance (ATR, Model: Miracle). In order to confirm the presence of Cefatoxime in the particles, FTIR spectra of the drug, blank microparticles, and Cefatoxime-loaded microparticles were recorded. Comparing all FTIR spectra, the presence of all the peaks of Cefotaxime in the spectrum of Cefatoxime-loaded microparticles was observed.

Preparation of Complex Microparticles and Drug-Loaded Microparticles

Poly(Q-co-VP)-1/AlgNa microparticles were prepared by dropping an aqueous sodium alginate solution (2.0% w/v) onto an aqueous poly(Q-co-VP) solution (1.5% w/v) containing Ca[Cl.sub.2] (36 mM) under gentle magnetic stirring at room temperature. Air-driven droplet generator (KdScientific, Switzerland) was employed and microparticles formed were collected by filtration followed by lyophilization. Microparticles containing Cefotaxime as drug model were prepared by the same process described above, by dissolving Cefotaxime into sodium alginate aqueous solution (2.2 X [10.sup.-6] g/mL) under magnetic stirring at room temperature.

Microscopic Observations

The morphology and surface appearance of the unloaded and loaded freeze-dried microparticles were evaluated by means of scanning electron microscopy. The microparticles were coated with gold-palladium and their external surface was examined with JEOL-FX 2000, Japan; using a 10 kV accelerating voltage. The average particle diameter of poly(Q-co-VP)-1/AlgNa microparticles was determined employing 150 polymeric microparticles using a Nikon Eclipse H550S Optical microscope, Japan.

Encapsulation Yield

For determination of encapsulation yield (EY) six batches of poly(Q-co-VP)-1/NaAlg polymeric microparticles were recollected and were evaluated in terms of

EY(%) = [[m.sub.mp]/([m.sub.D] + [m.sub.p])] x 100

where [m.sub.mp] is the mass of microparticles obtained in the process, [m.sub.D] and [m.sub.P] were the mass of drug and polymer initially dissolved in the solution.

Encapsulation Efficiency

Drug loading was determined by dispersing accurately weighed amounts of microparticles (10 mg) in 10 mL of distilled water. The supernatant was filtrated through 0.22 [micro]m membrane (Millipore) and the drug loading, expressed as weight of polymeric microparticles was determined in triplicate for each composition using UV/Vis spectrophotometer (Cintra 10e, Australia) at a wavelength of 236 nm. The percentage encapsulation efficiency (EE) was calculated as follows:

EE (%)= ([C.sub.mp]/[C.sub.0]) X 100

where [C.sub.mp] is the drug concentration in the microparticles, [C.sub.0] is the drug concentration in the initial solution which the microparticles were obtained.

In Vitro Release Studies

Previously to in vitro release studies, we recording absorbance of unloaded microparticles in simulated fluids and any absorption peak was observed in comparison with loaded microparticles, which showed a maximum peak absorption at 236 nm corresponding to Cefotaxime. In order to evaluate their potential as drug delivery system poly(Q-co-VP)-l/NaAlg polymeric microparticles were loaded with 20 mg of Cefotaxime. Lyophilized loaded-microparticles were introduced in a dialysis bag, which was placed in a vessel containing 100 mL of the simulated fluid at 37 [+ or -] 1[degrees]C (Bioblock Scientific, Switzerland) under gentle stirring. At selected time intervals, 1 mL released medium was collected and replaced with fresh release medium to guarantee sink conditions throughout the experiment. The scheme of using simulated fluid was as followed: first hour to pH 1.2 (SGF); second and third hours to pH 4.5 (mixing of simulated gastric and intestinal fluid); fourth hour to 42 h to pH 6.8 (SIF). Simulated fluids conditions were prepared according procedure described in USP26-NF21 [39]. The drug concentration release (DR) into the different media as a function of time was monitored by UV-spectrophotometry at 236 nm and expressed as shown below:

DR (%) = ([M.sub.t]/[M.sub.[infinity]]) x 100

where [M.sub.t] is the drug amount released at time "t" and [M.sub.[infinity]] is the total drug amount in the microparticles. All experiments were carried out in triplicate and release experiments in separated fluids were made under same procedure.

RESULTS AND DISCUSSION

Synthesis and Determination of Copolymer Composition by Potentiometric Analysis

The synthesis of poly(Q-co-VP) copolymers using various monomer feed ratios were carried out by free radical polymerization and the monomer composition expressed as weigh percentage is listed in Table 1. FTIR spectroscopy was used to confirm the success of polymerization reaction between Q and VP, and the spectra showed the presence of peaks corresponding to the functional groups of monomer units in the copolymer. In the FTIR spectrum shown in Fig. 1, the band shown in 3374 [cm.sup.-1] confirms the presence of NH stretch. The bands at 1728 [cm.sup.-1] (C=O stretching of ester group) and 1666 [cm.sup.-1] (C=O stretching of amide group) correspond to Q and VP blocks, whereas the band at 1160 [cm.sup.-1] can be assigned to the asymmetric stretching vibration of the C-O-C bridge. The presence of quaternary nitrogen group is indicated by the band at 952 [cm.sup.-1]. Additionally, CN absorption band appeared at 1476 [cm.sup.-1]. Other bands represent C-C and C-H vibrations of C[H.sub.2] and C[H.sub.3] groups.

It is known that properties of copolymers will highly depend on the relationship that exists between the monomers. Thus, the determination of the real composition of the copolymer was very important in this work. FTIR and NMR spectroscopy are powerful techniques used to determine copolymer composition. Nevertheless, due to the presence of chloride ions in Q molecule, our approach was to use an electrochemical method to determine the composition of Q in the copolymers (relationship Q:[Cl.sup.-] 1:1) [40]. To determine the mass of Q it is only necessary to know the volume of silver used in the final point of the titration which was determined by calculating the second derivate in the resulting potentiometric curves. The resulting compositions at high conversions with yield in the range 67-81% are listed in Table 1. We can notice that the yield of the copolymers decreased with increase of VP concentration in feed mixture. The tendency of the yield to be diminished with the increase of VP feed content has been reported for some acrylic systems because its reactivity differences [41], Nevertheless it remained high for the system studied.

Polyelectrolyte Complex Microparticles

The electrostatic attraction between the anionic carboxyl groups of the sodium alginate and cationic quaternary ammonium group of the Q leads to the formation of stable microparticles in presence of CaCh (Fig. 2). The optimization and control of systems variables were essential for obtaining homogeneous microparticles. In fact, changing the order addition of polyanion and polycation solutions affected the formation of stable microparticles. Thereby, preliminary studies were conducted in order to identify the optimum conditions for microparticles formation taking into consideration non-agglomeration, morphology and stability. Thus the following condition was achieved: poly(Q-co-VP) weight ratio 90:10, 0.08 g of cross-linking agent and 300 rpm stirring rate.

Macroscopic observation evidenced the formation of polyelectrolyte complex through turbid appearance in comparison to the initial colourless of dissolutions of both polyeletrolytes. Thus, in this work the formation of poly(Q-co-VP) and sodium alginate polyeletrolyte complex was conductimetrically followed. Conductimetry is a useful technique to study this process because complex formation is accompanied by the release of ionic specie (in our case NaCl) with different mobility in the medium, consequently resulting in increase of conductivity. This process can be shown as follows:

[FORMULA NOT REPRODUCIBLE IN ASCII]

Figure 3 shows the behavior of the conductivity of the mixture as a function of the molar fraction of the reaction system, Z ([Q-co-VP]/[AlgNa]), during the formation of the polyelectrolyte complex when a solution of sodium alginate is added to the copolymer solution. The value of the slope is not very high as it should be expected by the liberation of hydroxyl ions (O[H.sup.-]). This is due to the consumption of these ions with the course of the reaction, as a result of the equilibrium displacement represented before.

Microscopic Observations

The shape and surface morphology of freeze-dried microparticles prepared by complex coacervation were evaluated using scanning electron microscopy (Fig. 4). It can be seen that unloaded microparticles exhibited an irregular spherical shape with several wrinkles on their surface. Microparticles of similar appearance have been reported [42, 43], In the case of Cefotaxime-loaded microparticles change in the external morphology could be observed, showing more rough in comparison to unloaded poly(Q-co-VP)-1/AlgNa.

Particle size analysis was done by optical microscopy and the size of the microparticles was in the range 400-850 [micro]m. Homogenous size distribution (600 [+ or -] 100 [micro]m) was observed in Fig. 5 and no apparent change in particle size was observed after incorporation of Cefotaxime in poly(Q-co-VP)-1/NaAlg.

In Vitro Drug Release Study

The possible use of the hydrophilic system for colon specific oral drug delivery is based on that the sample must release the maximum amount of the drug at high pH, while minimum amount of drug at acid medium. Cefotaxime Sodium, as a drug model, was successfully entrapped inside microparticles, obtaining 79% of encapsulation efficiency due to solubility of the drug and the preparation method. The strong electrostatic interaction between opposite charges of polymer solutions with crosslinking by addition of Ca[Cl.sub.2] leads to a good encapsulation yield and an effective EE (Fig. 2). It is known that pH of the colon region is lower than that of small intestine due to acidification of colonic contents by the products of bacterial fermentation. In the case of severe IBD, the colonic pH often drops down to between 1 and 5 [44], In that direction, simulated small intestine fluid was included in the evaluation of release properties of the system as shown in Fig. 6. The release profile of Cefotaxime has indicated that the drug release was dependent of pH, characterized by increase of drug release with the increment of pH values.

This behavior could be explained based on the functional groups and the contributions of different forces as electrostatic interactions. So for better elucidation the release experiments were carried out in separated regime (Fig. 7). In acidic environment of the stomach (pH 1.2), all species are in protonated form experimenting crosslinking by hydrogen bonds leading formation of a more rigid network. This compact structure reduces movement of polymer chains within the hydrophilic network. As consequence, a retardation of drug release from microparticles was observed. That explains the lower aliquot of release in Simulated Gastric Fluid with a maximum accumulative release of the 24% at 7 h when compared with the percentage of drug released in Simulated Intestinal Fluid at the same time.

In contrast, in simulated intestinal fluid the higher drug release was observed with pH increment. At basic pH, the carboxylic acid groups in the sodium alginate structure are ionized causing an increment of the electrostatic repulsive force between the charged sites and more easy a drug is released. Nevertheless, taking into account that addition of divalent ions produces a partial neutralization of carboxylate groups on the alginate chain we considered a remarkable influence of quaternary ammonium groups at high pH. Two main interactions can influence over release process: the interaction of positive charges of Q with anionic charges present in the release medium and the electrostatic repulsion interactions of these free positive charges. However, screening effect of the counter ion focused the explication in the second interaction [45]. As explained before and considering the large number of positive charges present in the microparticles, the increasing electrostatic repulsive force produces more expansion of the polymeric matrix, giving rise a more open network and the subsequent release of Cefotaxime from system in a faster manner. In the case of SIF, the maximum accumulative release corresponded to 84% at 7 h. Zhang et al. [46] also observed this release pattern in Carboxymethylated Chitosan/Alginate microspheres and Serra et al. [47] in teophylline release from pH-sensitive poly(acrylic acid-g-ethylene glycol) hydrogels. Additionally Alvarez-Lorenzo et al. [48] reported similar release profiles of alginate as in our article remarking the important contribution of the combination of ionic polysaccharides and polymer as controlled release carrier for colon delivery of drugs.

Finally, although only one composition of the copolymer was used to study the release processes, the influence of VP over Cefotaxime release due to its amphiphilic character can be discuss. VP contains a highly polar amide group providing hydrophilicity and, as consequence, increase in the release behavior of the microparticles is observed. On the other hand, the presence of apolar methylene and methine groups in the backbone and the ring conferring hydrophobic properties cause the opposite effect over the release process. However, taking in consideration the predominant electrostatic interaction over release process as well as the high strong hydrophilic character of Q segments in comparison with hydrophilic group of VP, we focused the role in hydrophobic segments of VP. Considering these aspects, it is expected that increase in VP content causes a slight decrease over release profile of this system.

CONCLUSION

In this work, a new pH-sensitive microparticles has been successfully prepared using an inexpensive and simple method by combination of natural and synthetic polymers. Synthetic copolymer [poly(Q-co-VP)] was synthesized by free-radical polymerization at 60[degrees]C and their molecular structure was confirmed by FTIR and potentiometric analysis. A model drug (Cefotaxime) was loaded and its release was studied in various media simulating human gastrointestinal tract. Microparticles with sizes on the order of 600 [+ or -] 100 [micro]m showed a rough surface morphology and exhibited encapsulation efficiency around 80%. Results obtained from drug release experiments indicated that the drug is released slowly at acidic pH thus protecting the drug from the action of high acid conditions in stomach. In the intestine environment electrostatic interactions between the polymers play a remarkable role over release process, causing release of Cefotaxime in a controlled manner.

ACKNOWLEDGMENT

The authors acknowledge the support as Project CAPES/ MES Cuba 133-11.

REFERENCES

[1.] J. Liu, H. Bauer, J. Callahan, P. Kopeckova, H. Pan, and J. Kopecek, J. Control. Release, 143, 71 (2010).

[2.] A.K. Patri, J.F. Kukowska-Latallo, and J.R. Baker Jr., Adv. Drug Deliv. Rev., 57, 2203 (2005).

[3.] Y. Zhang, H.F Chan, and K.W. Leong, Adv. Drug Deliv. Rev., 65, 104 (2013).

[4.] F. Jia, X. Liu, L. Li, S. Mallapragada, B. Narasinham, and Q. Wang, J. Control. Release, 172, 1020 (2013).

[5.] Q. Zhao and B. Li, Nanomedicine, 4, 302 (2008).

[6.] C.M. Simonoska, D.M. Glavas, and K. Goracinova, Eur. J. Pharm. Biopharm., 68, 565 (2008).

[7.] M. Tavakol, E. Vasheghani-Farahani, and S. Hashemi-Najafabadi, Prog. Biomater., 2, 2 (2013).

[8.] N. Barbani, L. Lazzeri, C. Cristallini, M.G. Cascone, G. Polacco, and G. Pizzirani, J. Appl. Polym. Sci., 72 (1999).

[9.] Q. Wang, Z. Gu, S. Jamal, M.S. Detamore, and C. Berkland. Tissue Eng., 13, 2586 (2013).

[10.] Q. Wang, S. Jamal, M.S. Detamore, and C. Berkland, J. Biomed. Mater. Res., 96(3), 520 (2013).

[11.] V.G. Babak, E.A. Skotnikova, I.G. Lukina, S. Pelletier, P. Hubert, and E. Dellacherie, J. Colloid Interf. Sci., 225, 505 (2000).

[12.] A. Jain, S.K. Jain, N. Ganesh, J. Barve, and A.M. Beg, Nanomedicine, 6, 179 (2010).

[13.] M.K. Chourasia and S.K. Jain, J. Pharm. Pharmaceut. Sci., 6, 33 (2003).

[14.] M. Rodriguez, J.L. Vila-Jato, and D. Torres, J. Control. Release, 55, 67 (1998).

[15.] S.K. Bajpai, M. Bajpai, and K.G. Kalla, J. Appl. Polym. Sci., 84, 1133 (2002).

[16.] S.K. Bajpai and P. Banger, Polym. Eng. Sci., 53, 2129 (2013).

[17.] T.A. Sonia and C.P. Sharma, Adv. Polym. Sci., 243, 23 (2011).

[18.] K. Mladenovska, O. Cruaud, P. Richommed, E. Belamie, R.S. Raicki, M.C. Venier-Julienne, E. Popovski, J.P. Benoit, and K. Goracinova, Int. J. Pharm., 345, 59 (2007).

[19.] P. Bawa, V. Pillay, Y.E. Choonara, L.C. du Toit, V.M. Ndesendo, and P. Kumar, AAPS Pharm. Sci. Tech., 12, 227 (2011).

[20.] Z. Gu, A.A. Aimetti, Q. Wang, T.T. Dang, Y. Zhang, O. Veisseh, H. Cheng, R.S. Langer, and D.G. Anderson, ACS Nano., 7, 4194 (2013).

[21.] B. Buyuktimkin, Q. Wang, P. Kiptoo, J.M. Stewart, C. Berkland, and T.J. Siahaan, Mol. Pharm., 9(4), 979 (2012).

[22.] C.Y. Yu, X.C. Zhang, F.Z. Zhou, X.Z. Zhang, S.X. Cheng, and R.X. Zhuo, Int. J. Pharm., 357, 15 (2008).

[23.] R.D. Jayant, M.J. Me Shane, and R. Srivastava, Drug Deliv., 16, 331 (2009).

[24.] M. George and T.E. Abraham, J. Control. Release, 114, 1 (2006).

[25.] M.P.A. Lim, W.L. Lee, E. Widjajab, and S.C.J. Loo, Biomater. Sci., 1, 486 (2013).

[26.] P.V. Finotelli, D. Da Silva, M. Sola-Penna, A.M. Rossi, M. Farina, L.R. Andrade, A.Y. Takeuchie, and M.H. Rocha-Leao, Colloid. Surf. B: Biointeif, 81, 206 (2010).

[27.] W. Jaeger, J. Bohrisch, and A. Laschewsky, Prog. Polym. Sci., 35, 511 (2010).

[28.] Y.S. Kim, H.W. Kim, S.H. Lee, K.S. Shin, H.W. Hur, and Y.H. Rhee, Int. J. Biol. Macromol., 41, 36 (2007).

[29.] B. Dizman, M.O. Elasri, and L.J. Mathias, Macromolecules, 39, 5738 (2006).

[30.] N. Kang and J.C. Leroux, Polymer, 45, 8967 (2004).

[31.] A. Veeren, A. Bhaw-Luximon, and D. Jhurry, Eur. Polym. J., 49, 3034 (2013).

[32.] L.A. Nud'ga, V.A. Petrova, N.V. Klishevich, L.S. Litvinova, A.Y. Babenko, and V.N. Shelegedin, Russ. J. Appl. Chem., 75, 1678 (2002).

[33.] M.J. O'Connell, P. Boul, L.M. Ericson, C. Huffman, Y. Wang, E. Haroz, C. Kuper, J. Tour, K.D. Ausman, and R.E. Smalley, Chem. Phys. Lett., 342, 265 (2001).

[34.] A.K. Anal, W.F. Stevens, and C. Remunan-Lopez, Int. J. Pharm., 312, 166 (2006).

[35.] A.H. El-Kamel, A.A. Abdel-Aziz, A.J. Fatani, and H.I. El-Subbagh, Int. J. Pharm., 358, 248 (2008).

[36.] G. Carja, S. Dranca, and G. Lehutu, Rev. Chim., 61, 27 (2010).

[37.] B. Singh. N. Chauhan, S. Kumar, and R. Bala, Int. J. Pharm., 352, 74 (2008).

[38.] S. Vasiliu, M. Popa, and C. Luca, Eur. Polym. J., 44, 3894 (2008).

[39.] R. Pandey, Z. Ahmad, S. Sharma, and G.K. Khuller, Int. J. Pharm., 301, 268 (2005).

[40.] S. Dragan and M. Cristea, Polymer, 43, 55 (2002).

[41.] G.T. Chen, C.H. Wang, J.G. Zhang, Y. Wang, R. Zhang, F.S. Du, N. Yan, Y. Kou, and Z.C. Li, Macromolecules, 43, 9972 (2010).

[42.] L. Aguero, J. Garcia, O. Valdes, G. Fuentes, D. Zaldivar, M.D. Blanco, and I. Katime, J. Appl. Polym. Sci., 128, 3548 (2013).

[43.] I. Panos, N. Acosta, and A. Heras. Curr. Drug Discov. Technol., 5, 333 (2008).

[44.] K. Kaur and K. Kim, Int. J. Pharm., 366, 140 (2009).

[45.] G.R. Mahdavinia, A. Pourjavadi, H. Hosseinzadeh, and M.J. Zohuriaan, Eur. Polym. J., 40, 1399 (2004).

[46.] L. Zhang, J. Gou, X. Peng, and Y. Jin, J. Appl. Polym. Sci., 92, 878 (2004).

[47.] L. Serra, J. Domenech, and N.A. Peppas, Biomaterials, 27, 5440 (2006).

[48.] C. Alvarez-Lorenzo, B. Blanco-Fernandez, A.M. Puga, and A. Concheiro, Adv. Drug Deliv. Rev., 65, 1148 (2013).

L. Aguero, (1) D. Zaldivar, (1) L. Pena, (1) Y. Solis, (1) J.A. Ramon, (1) Marcos L. Dias (2)

(1) Departamento de Quimica Macromolecular, Centro de Biomateriales, Universidad de La Habana, Ave. Universidad % G y Ronda, CP 10400, Ciudad de La Habana, Cuba

(2) Universidade Federal do Rio de Janeiro, Instituto de Macromoleculas Professora Eloisa Mano, Av. Horacio Macedo, 2030-Centro de Tecnologia. Bioco J, Rio de Janeiro, RJ, Brazil

Correspondence to: Marcos L. Dias; e-mail: mldias@ima.ufrj.br

DOI 10.1002/pen.23962

Published online in Wiley Online Library (wileyonlinelibrary.com).

TABLE 1. Data of radical polymerization of Q and VP and copolymer
composition of poly (Q-co-VP) by potentiometric analysis.

                   Q/VP feed
                  composition   Q in copolymer   Yield
Sample               (wt%)          (wt%)         (%)

Poly(Q-co-VP)-1      90/10           89.2         81
Poly(Q-co-VP)-2      80/20           79.2         74
Poly(Q-co-VP)-3      60/40           57.4         67
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Author:Aguero, L.; Zaldivar, D.; Pena, L.; Solis, Y.; Ramon, J.A.; Dias, Marcos L.
Publication:Polymer Engineering and Science
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Date:May 1, 2015
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