In Situ Incorporation of Praziquantel in Polymer Microparticles through Suspension Polymerization for Treatment of Schistosomiasis

Abstract

Schistosomiasis is one of the major public health problems worldwide. Even though this is a common illness among preschool children in poor countries, treatment is carried out mainly through the administration of praziquantel tablets, which has some disadvantages, such as the strong bitter taste. As an alternative to overcome this problem, the development of new encapsulated praziquantel formulations is demanded. For this reason, suspension polymerizations are carried out for the in situ encapsulation of praziquantel into polymer microparticles, using methyl methacrylate (MMA) and cationic compounds (diethylaminoethyl methacrylate, DEAEMA, and dimethylaminoethyl methacrylate, DMAEMA) as comonomers. This technique allows for the preparation of polymer microparticles with high encapsulation efficiencies (>90%) with characteristic sizes ranging from 0.5 to 1500 µm. Drug release profiles show that praziquantel is released from poly(methyl methacrylate) microparticles slowly due to the existence of strong diffusional resistance. On the other hand, the addition of cationic comonomers renders polymer particles sensitive to pH variations, allowing for faster release of praziquantel in acidic environments, as found in the stomach.

Development of Smart Polymer Microparticles through Suspension Polymerization for Treatment of Schistosomiasis

“…This behavior is probably due to the increase of the viscosity of the organic phase when PZQ is added, which affects the rates of breakage and coalescence of the particles. Similar behavior was reported by Paiva et al and Oliveira et al, when PZQ and doxorubicin were incorporated into microparticles through suspension polymerizations of MMA and suspension copolymerizations of vinyl acetate and MMA, respectively.…”

“…Figure 3 and Table 2 present the particle size distributions and mean diameters, respectively, of the produced microparticles. As it can be observed, all particles presented the characteristic micrometric size, as expected for particles produced through suspension polymerizations, indicating that addition of the cationic comonomers to the suspended organic mixture did not prevent the successful formation of the polymer microparticles, as also reported previously for reactions performed in the presence of lower comonomer contents . Besides, one can note the shifting of particle size distributions toward larger particle sizes with the increase of the comonomer contents, due tvo increase of rates of particle coalescence, as shown in the next paragraphs.…”

“…First of all, it is important to mention that praziquantel presents excellent thermal stability, showing maximum rate of thermal degradation near 300 °C, which guarantees its safe manipulation and stability in the suspension polymerization trials, performed at 80 °C …”

“…In order to verify the pH‐sensitive response, dissolution tests were conducted at two different media: in intestinal environment (phosphate buffer pH 6.8) and in the gastric environment (HCl 0.1 m pH 1.2). The tests were performed using the same methodology described previously by Paiva et al and recommended by distinct Pharmacopeias.…”

“…Particularly, a previous work showed that it is possible to produce smart microparticles, loaded with PZQ and presenting suitable properties for biomedical applications, through suspension polymerization reactions in the presence of low cationic comonomer contents (below 10 wt%). For this reason, the present work investigates the manufacture of pH‐sensitive smart microparticles through copolymerization of methyl methacrylate (MMA) and the cationic comonomers diethylaminoethyl methacrylate (DEAEMA) or dimethylaminoethyl methacrylate (DMAEMA) in broader ranges of comonomer feed compositions (0 to 40 wt%).The obtained results indicate that microparticles with sizes in the range of 10–1100 µm can be produced successfully, allowing high PZQ encapsulation efficiencies (>80%).…”