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

Abstract

Schistosomiasis is a neglected tropical disease that affects primarily the poorest and most vulnerable populations. Although praziquantel (PZQ) is the drug used most frequently for treatment of schistosomiasis, PZQ presents unpleasant bitter taste and low solubility in water, which prejudice the implementation of pediatric treatments. For this reason, the main purpose of the present work was the production of stable nanoparticles loaded with PZQ through in situ miniemulsion copolymerizations of methyl methacrylate (MMA) with diethylaminoethyl methacrylate (DEAEMA) or dimethylaminoethyl methacrylate (DMAEMA). Due to the cationic nature of the comonomers, the use of different ionic surfactants was also investigated. Nanoparticles with narrow particle size distributions, characteristic average diameters ranging from 50 nm to 110 nm, and loaded with 20 wt% of PZQ were manufactured successfully PZQ encapsulation efficiencies were higher than 97 wt% and PZQ was homogeneously dispersed in the final polymer matrix. Finally, the use of a cationic surfactant with DEAEMA cationic comonomer led to more stable latexes because of the high absolute value of the zeta potential.

In Vitro Release and In Vivo Pharmacokinetics of Praziquantel Loaded in Different Polymer Particles

“…In this context, the slight reduction in entrapment efficiency of smart microparticles can be explained by the increase in hydrophilicity of the organic phase as a result of the presence of hydrophilic cationic comonomers [41]. In general, the obtained results are consistent with the literature [18,[20][21][22].…”

“…Figure 2 shows the release profiles of PZQ from the different polymer matrices. As expected, the protonation of the comonomers at lower pH values led to swelling of the particles and faster release of the drug, as reported previously for other microscopically dispersed systems [6,22,[42][43][44]. It is important to mention that the smart microparticles exhibited PZQ release rates that were higher than the ones observed for PMMA nanoparticles, emphasizing the existence of chemical and physicochemical characteristics that can balance the presumably higher diffusional resistance offered by the larger microparticles.…”

“…It is important to mention that PZQ presents high thermal stability, with a maximum degradation rate of around 300 • C, which ensures the stability of the drug at the reaction temperatures employed in the present work [20][21][22]. It is important to highlight that all samples were prepared and analyzed in triplicates to observe reproducibility, which was always better than 5%.…”

“…The obtained results showed that the rate of release of PZQ depended strongly on the feed composition and was very slow when pure PMMA was used as the polymer matrix. PAIVA et al [20,21] and ALVES et al [22] developed smart pH-responsive polymer micro-and nanoparticles [23], using 2-di(ethylamino)ethyl methacrylate (DEAEMA) and 2-di(methylamino)ethyl methacrylate (DMAEMA) as comonomers, and showing that the produced particles were pH-sensitive and that the drug release would preferentially occur in the acidic portions of the gastrointestinal tract. In fact, DMAEMA and DEAEMA polymers and copolymers have been used by others to produce materials that are sensitive to pH as a result of the ionizable pending groups that are present in the polymer chains [24].…”

In situ encapsulation of biologically active ingredients into polymer particles by polymerization in dispersed media

“…Furthermore, a pharmacokinetic study on rats showed improved bioavailability of the drug encapsulated in the NPs compared to a suspension of HPCT, which is promising for the use these NPs as oral drug delivery nanocarriers. Styrene (S) and MMA-based matrices are commonly used for the entrapment of hydrophobic active ingredients [87][88][89][90][91][92] via direct miniemulsion polymerization at high solids content (around 10-20 wt %), using AIBN or KPS as initiator. As discussed previously, a comonomer can be introduced to adjust the hydrophilicity of the polymer matrix and improve the EE.…”