The effect of encapsulated amount of caffeine on the mechanism of its release from hydrogels based on poly(methacrylic) and casein

Researchers are making everyday efforts to develop new drugs or improve present ones in order to enhance therapies of various diseases, especially serious ones like cancer. Drug delivery systems (DDS) are one of the solutions for safer and more efficient therapy. Hydrogels based on poly(methacrylic acid) (PMAA) are extensively investigated as DDS due to their nontoxicity, biocompatibility and pH sensitivity. Many chemotherapeutics are poorly watersoluble, so it is quite challenging to encapsulate them into highly hydrophilic PMAA. In our previous study we overcome this limitation by modifying PMAA with amphiphilic casein and demonstrated that poorly water-soluble model drug – caffeine can be successfully encapsulated and released in control manner from these samples (H hydrogels). In present study we go step forward and investigated how the change in the amount of encapsulated caffeine affect the mechanism of caffeine release from the H hydrogels in medium with pH of 6.8 (which simulates the environment in human intestines). Commonly used models for the analysis of kinetics of drug release from hydrogels: Ritger-Peppas, Higuchi and Kopcha model are employed for the analysis of the mechanism of caffeine release. Presented results indicate that it is possible to adjust the manner and mechanism of drug release by changing the amount of encapsulated drug, due to which the H hydrogels can adapt to the unique requirements of the therapy

Photoelectrochemical properties of sol–gel obtained titanium oxide

The photoelectrochemical properties of a sol–gel prepared titanium oxide coating applied onto a Ti substrate were investigated. The oxide coating was formed from an inorganic sol thermally treated in air at 350 °C. The coating consisted of agglomerates of narrow size distribution around 100 nm. The photoelectrochemical characteristics were evaluated by investigating the changes in the open circuit potential, current transients and impedance characteristics of a Ti/TiO2 electrode upon illumination by UV light in H2SO4 solution and in the oxidation of benzyl alcohol. The electrode was found to be active for photoelectrochemical reactions in the investigated solutions

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

pH-sensitive hydrogels based on poly(methacrylic acid), casein and liposomes for targeted delivery of poorly water-soluble active substances

Polymeric carriers for targeted delivery of poorly water-soluble active substances (PWSAS) are facing two challenges. First, encapsulation of PWSAS depends on structure of the carrier. Second limitation is caused by the phenomenon of burst drug release. Despite the fact that the fast release of drug in a burst stage is utilized in certain drug administration strategies, the negative effects brought about by burst can be pharmacologically dangerous and economically inefficient. This study presents a novel strategy for encapsulation and targeted delivery of PWSAS - caffeine without the possibility of burst effect. Hydrophilic carrier based on poly(methacylic acid) was modified by amphiphilic substances - casein and centrifuged liposomes to ensure caffeine encapsulation. The caffeine was encapsulated in liposomes which further were incorporated into the carrier networks during the synthesis of the carriers. The release kinetic of caffeine was analyzed with respect to morphology of the carriers and interactions that could be established between the components of the carrier. The swelling of carriers and release of caffeine were further investigated depending on the neutralization degree of methacrylic acid in two media with different pH simulating the path of the carrier through the upper and lower human gastrointestinal tract. Synthesized carriers showed significant potential for encapsulation and targeted delivery of PWSAS.Kod razvoja polimernih nosača za ciljano otpuštanje slabo vodorastvornih aktivnih supstanci (SVAS) postoje dva ograničenja. Prvo, inkapsulacija SVAS zavisi od strukture nosača. Drugo ograničenje je vezano za naglo oslobađanje leka. Uprkos činjenici da je naglo oslobađanje leka, tzv. burst efekat poželjno kod nekih sistema, negativni efekti naglog oslobađanja leka u većini slučajeva mogu biti farmakološki opasni i ekonomski neefikasni. U ovom radu je prikazana nova strategija za inkapsulaciju i ciljano otpuštanje SVAS – kofeina bez burst efekta. Hidrofilni nosač na bazi poli(metakrilne kiseline) je modifikovan amfifilnim supstancama – kazeinom i centrifugiranim lipozomima kako bi se postigla inkapsulacija kofeina. Kofein je inkapsuliran u lipozome koji su zatim inkorporirani u mrežu nosača tokom sinteze nosača. Analiziran je uticaj morfologije nosača i interakcija koje su se uspostavile između njegovih komponenti na kinetiku otpuštanja kofeina. Zatim je analiziran uticaj stepen neutralizacije metakrilne kiseline na bubrenje nosača i otpuštanje kofeina u dve sredine različitih pH vrednosti koje su simulirale pH sredinu u gastrointestinalnom traktu čoveka. Pokazano je da sintetisani nosači imaju veliki potencijal za inkapsulaciju i ciljano otpuštanje SVA

Three dimensional polymeric networks based on poly(methacrylic acid) and protein for targeted delivery of poorly water-soluble drugs

Three dimensional polymer networks, hydrogels, have shown a great potential in controlled release and targeted delivery of active substances. pH sensitive hydrogels based on poly(methacrylic acid) have attracted significant attention due to their biocompatibility, non-toxicity and the possession of the huge number of ionogenic carboxylic groups. On the other hand, the usage of these hydrogels for controlled release and targeted delivery of poorly water-soluble drugs is limited by their highly hydrophilic nature. We overcame this limitation by modifying PMAA with amphiphilic substance - casein. The addition of this natural protein enabled the encapsulation, targeted delivery and controlled release of poorly water-soluble model drug - caffeine. Three carriers with different neutralization degree of methacrylic acid were synthesized via free radical polymerization. The FTIR spectra revealed that two types of interactions were established between casein and caffeine: hydrophobic interactions and hydrogen bonds. The SEM micrographs showed that the structure of the carriers depended on the change of neutralization degree of the methacrylic acid. The swelling of synthesized carriers and the caffeine in vitro release were monitored in two environments at 37°C: 0.1M HCl pH=1.2 (simulation of environment in human stomach) and phosphate buffer pH=6.8 (simulation of environment in human intestines). The synthesized carriers had higher swelling degree and the higher release rate of caffeine in the phosphate buffer pH=6.8 than in 0.1M HCl. The increase in neutralization degree of methacrylic acid caused the increase in swelling degree of the carriers and the increase in release rate of caffeine. Presented results showed that synthesized carriers are promising candidates for targeted delivery of poorly water-soluble drugs

Effect of crosslinker amount on hybrid hydrogels swelling and drug release

Targeted drug delivery is powerful tool which researchers use to achieve safer and more efficient therapy of many diseases, including various types of cancer. Many chemotherapeutics are poorly watersoluble, so their encapsulation and targeted delivery remain quite challenge. Hydrogels based on poly(methacrylic acid) (PMAA) are widely investigated for targeted drug delivery due to their pH sensitivity, non-toxicity and biocompatibility. Still, due to the PMAA highly hydrophilic nature, PMAA can only be used for encapsulation and targeted delivery of water-soluble drugs. Our previous research was directed towards overcoming this limitation: PMAA was modified with amphiphilic protein – casein and poorly-water soluble model drug – caffeine – was encapsulated (PMAC). Present study is focused on investigation how variation of amount of one of the most important hydrogels network parameter such as crosslinker affect PMAC swelling properties and caffeine release. The group of hybrid hydrogels – PMAC – was synthesized with various amount of crosslinker: 0.4mol%, 0.8mol%, 1.6mol% and 3.2mol% with respect to methacrylic acid. Swelling behavior of hybrid hydrogels and caffeine release was investigated in two environments which simulated human stomach and intestines. Obtained results showed that targeted delivery of poorly water-soluble model drug was achieved and that its release can be prolonged up to 24h. Also, kinetic of poorly water-soluble drug release can be easily modified only by changing crosslinker amount. PMAC hybrid hydrogels have huge potential for targeted delivery of poorly water-soluble active substances

Effect of neutralization degree of methacrylic acid on hydrogel swelling and drug release

Drug delivery system is an amazing tool which is widely used for drug protection and its controlled release in order to enhance drug bioavailability, reduce side effects and therefore to improve overall therapy. Hydrogels have been attracted great attention as drug carriers due to their great physicochemical properties, similarity to the living tissues and biocompatibility. One group of pH sensitive hydrogels are based on poly(methacrylic acid) (PMAA). These non-toxic hydrogels are used as drug delivery system because they swell as a response to the change in pH of external environment and drug is being released during the process. In present study, in order to improve the control of drug release rate, caffeine was encapsulated in liposomes which were further embedded into PMC hydrogel (PMCL). It was investigated how the change in neutralization degree of methacrylic acid affect the swelling degree of PMCL hydrogels and caffeine release in two environments at 37 °C for 24 h: 0.1 M hydrochloride acid (pH 1) and phosphate buffer with pH value of 6.8 (pH 6.8), as a simulation of pH environment in human stomach and intestines, respectively. Obtained results show that PMCL hydrogels have great potential for controlled release of poorly water-soluble drugs in human intestines

Modification of hydrophilic polymer network to design a carrier for a poorly water-soluble substance

pH sensitive, nontoxic, and biocompatible poly(methacrylic) acid (PMAA) based soft networks have been extensively used in the design of systems for targeted drug delivery. Still, their highly hydrophilic nature limits their potential to be used as a carrier of poorly water-soluble substances. With the aim to overcome this limitation, the present study details a new approach for modification of PMAA based carriers using two amphiphilic components: casein and liposomes. The FTIR analysis revealed structural features of each component as well as the synergetic effect that originated from the formation of specific interactions. Namely, hydrophobic interactions between the poorly water-soluble model drug (caffeine) and casein enabled caffeine encapsulation and controlled release, while addition of liposomes ensured better control of the release rate. The morphological properties of the carriers, swelling behavior, and release kinetics of caffeine were investigated depending on the variable synthesis parameters (neutralization degree of methacrylic acid, concentration of caffeine, presence/absence of liposomes) in two different media simulating the pH environment of human intestines and stomach. The data obtained from in vitro caffeine release were correlated and analyzed in detail using several mathematical models, indicating significant potential of investigated carriers for targeted delivery and controlled release of poorly water-soluble substances

Methacrylic Acid Based Polymer Networks with a High Content of Unfunctionalized Nanosilica: Particle Distribution, Swelling, and Rheological Properties

The poor stability and tendency to agglomerate of unfunctionalized nano-SiO₂ in the presence of ionic species presents a challenge for preparing poly­(methacrylic acid)/nano-SiO₂ nanocomposite (NC) hydrogels with desired strength and swelling capability. We proposed a facile and eco-friendly method for the preparation of PMAA/SiO₂ NC hydrogels using unfunctionalized silica nanoparticles (NPs) in the form of a suspension. SEM and TEM analyses showed that the NP distribution in the polymer matrix highly depended on the particle concentration. At lower concentrations (up to 13.9 wt %), the NPs were uniformly dispersed as single nanoparticles. With an increase in NP concentration, homogeneously dispersed nanoscale aggregates were formed, while a further increase in the silica concentration led to the formation of homogeneous structures consisting of mutually interacting nanosilica particles coated with PMAA. Swelling experiments confirmed that the silica NPs behaved as adhesive fillers that interacted with PMAA chains, causing the formation of a thin polymer layer strongly adsorbed at the particle interface. The thicknesses of the adsorbed polymer layer, as well as the swelling kinetic parameters, were strongly influenced by nanoparticle size and concentration. Combining nanosilica and PMAA in the form of a soft hydrogel network provided stabilization of the NPs and ensured better mechanical properties of the obtained NC hydrogels compared to pure polymer matrix. The optimal loadings, necessary to ensure the most improved dynamical-mechanical properties, were found in the case of the formation of homogeneously dispersed, nanosized silica aggregates in a PMAA matrix

Removal of model cationic dye by adsorption onto poly(methacrylic acid)/zeolite hydrogel composites: Kinetics, equilibrium study and image analysis

Composites based on poly(methacrylic acid) (PMAA) and two types of zeolite, hydrophilic zeolite A and hydrophobic zeolite ZSM-5, were synthesized. The obtained hydrogel composites that combine well the strong interaction between PMAA and cationic species, the accessibility of active sites in the swollen network and fine mechanical stability of zeolites are considered promising candidates for removal of cationic dye, basic yellow 28 (BY28) from aqueous solutions. The adsorption was found to be highly dependent on composition of hydrogel composites, initial dye concentration, solution pH, sorbent mass and temperature, while the effect of zeolite type is less manifested. It was found that the surface adsorption influenced the kinetics of adsorption which was determined by the rate of movement of the boundary layer of BY28 adsorbed on hydrogel surface. Adsorption processes were found to be favorable and preferably physical in nature with maximum adsorption capacity that could reach up to 180 mg/g for PMAA/30A hydrogel composite. Image analysis was applied on differently colored hydrogels and revealed the linear correlation between equilibrium adsorption capacities and the mean values of pixel intensity, as well as the strong effect of initial dye concentration on uniformity of coloration along the hydrogel diameter