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

Abstract

Schistosomiasis is a parasitic disease that affects millions of people, especially low‐income people, and is considered a major public health problem in underdeveloped countries. The drug used most often for the treatment of the disease is praziquantel (PZQ), which has a strong and characteristic bitter taste that makes treatment of children inconvenient. For this reason, the present work investigates the development of smart pH‐sensitive polymer microparticles produced through suspension polymerizations to be used as vehicles for the controlled release of praziquantel in the body. The microparticles are produced through copolymerization of methyl methacrylate and the cationic comonomers diethylaminoethyl methacrylate or dimethylaminoethyl methacrylate. The obtained results indicate that microparticles with sizes in the range of 10–1100 µm can be formed successfully, allowing high PZQ encapsulation efficiencies (>80%). Zeta potential analyses and drug release assays confirm the pH‐sensitive responses of the cationic copolymers, leading to effective release of PZQ (around 80% in pH 1.2) in acidic media that simulate the organic fluids present in the stomach.

In situ encapsulation of praziquantel through methyl methacrylate/diethylaminoethyl methacrylate and MMA/DMAEMA miniemulsion copolymerizations in presence of distinct ionic surfactants

“…The obtained results support the assumption of protonation of the tertiary amine groups, as the nanoparticles surfaces became more positive when the pH decreased, indicating the occurrence of pH‐dependent surface charges. This behavior has been described previously for similar cationic copolymers by HU et al [ 24 ] and PAIVA et al [ 15 ] confirming indirectly the incorporation of the comonomer.…”

“…[ 19,21,50 ] On the other hand, PDEAEMA and PDMAEMA homopolymers exhibit T g values around 20°C. [ 34,35 ] The incorporation of the comonomer exerted little impact on T g values, as also observed by Paiva et al, [ 15 ] which is in fair accordance with the Fox Equation (assuming the homogeneous comonomer incorporation) and indicates that formation of long comonomer blocks was unlikely. However, nanoparticles prepared with PZQ presented lower T g values (close to 75°C), suggesting that PZQ exerts a plasticizing effect on the polymer matrix.…”

“…Particularly, PZQ can act as a chain transfer agent because of its multiple functional groups, as already reported in the literature. [ 2,14 ] The presence of the comonomer also affected the molecular weight distributions of the final products, [ 14,15 ] although the shifting towards lower molecular weights in presence of PZQ could be observed in all cases. In particular, the polydispersity index of products prepared with CTAB tended to be larger than the ones obtained with SDS, which also indicates that the surfactant can affect the kinetics of reaction in MMA miniemulsion polymerizations performed in presence of PZQ.…”

“…These concentrations were defined in accordance with previous MMA miniemulsion polymerization [ 32 ] and PZQ encapsulating studies in PMMA nanoparticles, [ 2 ] PMMA microparticles [ 33 ] and MMA‐based copolymer microparticles. [ 14,15 ] The initial miniemulsion was prepared through sonication with ice‐bath, using a sonicator provided by Branson (Branson 450, Marshall Scintific, Hampton, USA) at 160 W for 5 min. Polymerizations were conducted in a 100 ml glass reactor (EasyMax 102, Mettler Toledo, Ohio, USA) at 80 °C under agitation of 500 rpm for 180 min.…”

“…[ 12,13 ] Encapsulation of PZQ in polymer nanoparticles and microparticles also constitutes a promising alternative for enhancement of PZQ dissolution rates in body fluids and masking of the inherent bitter taste. [ 2,8,14–16 ] Particularly, nanotechnologies have helped the development of more efficient drug delivery systems, expanding the range of pharmaceutical formulation products. [ 17,18 ] As a matter of fact, encapsulation of drugs in polymer nanoparticles can improve the bioavailability of poorly soluble drugs, allow control of drug release rates, enhance the chemical and physical stabilities of biocompounds and mask the unpleasant taste of loaded species.…”