Funkcionalnost hitozana u formulaciji alginat-hitozan mikročestica kao nosača za nesteroidne antiinflamatorne lekove

Abstract

Prednosti mikročestica u odnosu na konvencionalne nosače lekovitih supstanci ogledajuse u sferičnom obliku, velikom odnosu površine i volumena, mikrometarskimdimenzijama, raznovrsnosti materijala za njihovu izradu i postupakamikroinkapsulacije. Poseban značaj imaju mikročestice izrađene od prirodnih,biodegradabilnih i biokompatibilnih polimera, poput alginata, koji formiraju gelove uprisustvu Ca2+ jona. Međutim, poroznost Ca-alginatnih hidrogel mikročestica iosetljivost na prisustvo sekvestrirajućih jona može uzrokovati brzo otpuštanjeinkapsulirane lekovite supstance. Ove nedostatke je moguće prevazići tretiranjem Caalginatnihgelova sa katjonskim polimerima, poput hitozana, koji sa alginatima obrazujupH osetljive polielektrolitne komplekse.U predstavljenom radu izvršena je fizičkohemijska, farmaceutsko-tehnološka ibiofarmaceutska karakterizacija Ca-alginatnih mikročestica izrađenih metodomeksternog geliranja i tretiranih hitozanima različitih molekulskih masa, u ciljupoboljšanja karakteristika konvencionalnih Ca-alginatnih mikročestica. Posebna pažnjausmerena je ka ispitivanju uticaja molekulske mase hitozana na njihovu funkcionalnostu formulaciji alginat-hitozan mikročestica kao nosača za nesteroidne antiinflamatornelekove.U prvoj fazi korišćeni su hitozani velike molekulske mase (50 – 375 kDa).Rezultati karakterizacije mikročestica podvrgnuti su analizi primenomeksperimentalnog dizajna, kako bi se došlo do zaključaka o uticaju molekulske masehitozana i drugih formulacionih faktora na karakteristike mikročestica, kao i njihovihmeđusobnih interakcija. Primenom hitozana velikih molekulskih masa izrađene sumikročestice blago deformisanog sferičnog oblika, mikrometarskih dimenzija, sarelativno visokom efikasnošću inkapsulacije (> 75 %) i profilima oslobađanja koji seodlikuju zanemarljivim oslobađanjem naproksena u kiseloj sredini. Međutim, rezultati ove faze su otkrili da primenu hitozana velike molekulske mase otežavaju izraženviskozitet njihovih vodenih rastvora i dužina lanaca koji ograničavaju njihovo vezivanjena površinu Ca-alginatne mikročestica...

In comparison with conventional drug delivery systems microparticles offer severaladvantages such as: micrometric dimensions, spherical shape and great surface tovolume ratio. Furthermore, numerous materials and different encapsulation techniquescan be used to obtain microparticles with desired characteristics. There is growinginterest for microparticles consisted of natural, biodegradable and biocompatiblepolymers such as alginates, which can form gels in presence of Ca2+ ions. However, Caalginatehydrogels are porous and sensitive on presence of sequestering agents, whichcan cause fast release of encapsulated drug. In order to overcome these limitations Caalginatemicroparticles can be treated with cationic polymers such as chitosan.In the presented work alginate-chitosan microparticles were prepared byionotropic gelation followed by polyelectrolyte complexation and subjected to detailphysicochemical, biopharmaceutical and pharmaceutical characterization with the aimto investigate the ability of chitosan to improve characteristics of conventional Caalginatemicroparticles. The special interest was to assess the influence of chitosanmolecular weight on chitosan functionality in formulation of alginate-chitosanmicroparticles as drug delivery systems for NSAILs.In the first phase Ca-alginate microparticles were treated with high molecularweight chitosans (50 – 375 kDa). Experimental design analysis was used to investigatethe effect of chitosan molecular weight, other formulation factors and their interactionson microparticles properties. Obtained particles exhibited micrometric size, slightlydeformed spherical shape and relatively high encapsulation efficiencies (> 75 %).Release of encapsulated naproxen in simulated gastric fluid was negligible. However,the obtained results revealed some disadvantages of high molecular weight chitosans,such as: high viscosity of their water solutions and their limited ability to formpolyelectrolyte complex (PEC) with alginate only on particles surface...