| Abstract | Melatonin je hormon epifize s primarnom ulogom regulacije cirkadijanog ritma organizma. Usto, pokazuje izražena antioksidativna svojstva, antitumorsko te imunostimulativno djelovanje. Bioraspoloživost oralno primijenjenog melatonina mala je i promjenjiva, zahvaljujući izraženom metabolizmu prvim prolaskom kroz jetru. Usto, melatonin se brzo izlučuje iz organizma. Stoga su suvremena istraživanja fokusirana na razvoj terapijskih sustava prikladnih za primjenu melatonina putem različitih sluznica i kože, s ciljem poboljšanja njegovih farmakokinetičkih svojstava i optimiranja njegovog sistemskog ili lokalnog učinka. Cilj ovog rada bio je pripraviti nanočestice za topikalnu primjenu melatonina, sa zadovoljavajućim postotkom uklapanja melatonina i produljenim oslobađanjem. Za njihovu pripremu korišteni su lecitin S100 (>94 % fosfatidilkolina), kationski lipid dimetil-dioktadecil-amonijev bromid (DDAB) i natrijev alginat. Lipidno-alginatne nanočestice pripravljene su ionskom interakcijom negativno nabijenog natrijevog alginata i pozitivno nabijene smjese lecitina i DDAB. S ciljem optimiranja svojstava nanočestica, variran je maseni omjer DDAB, lecitina i natrijevog alginata u pripravi nanočestica. Lecitinske nanočestice pripravljene od lecitina S100 karakterizirane su negativnim zeta-potencijalom koji iznosi -5,0±2,7 mV, te veličinom od 72,1±0,2 nm. Dodatak kationskog lipida DDAB u masenom omjeru prema lecitinu 0,5:50 rezultirao je formiranjem nanočestica pozitivnog naboja. Lipidno-alginatne nanočestice karakterizirane su negativnim zeta-potencijalom u rasponu od -0,2±1,4 do -30,6±1,0 mV, te veličinom od 108,3±1,5 do 295,0±5,4 nm. Na njihovu veličinu i zeta-potencijal utjecao je maseni omjer DDAB, lecitina i natrijevog alginata. Za uklapanje melatonina odabrane su lipidno-alginatne nanočestice s omjerom DDAB i lecitina od 0,7:50, 1:50, 3:50 i 5:50 te masenim omjerom lecitina i alginata 50:5. Odabrane nanočestice karakterizirane su zeta-potencijalom negativnijim od -16 mV. Uspješnost uklapanja melatonina iznosila je od 23,8 do 32,1 %. Nanočestice s najvećim omjerom DDAB i lecitina (5:50) karakterizirane su najvećom uspješnošću uklapanja, koja je rezultirala koncentracijom melatonina u suspenziji nanočestica od 129,7±4,7 g/ml. Lipidno-alginatne nanočestice karakterizirane su produljenim oslobađanjem melatonina. |
| Abstract (english) | Melatonin is a pineal gland neurohormone, with primary role in regulation of circadian rhythm. In addition, it has prominent antioxidative, anticancer and imunostimulative properties. Melatonin oral bioavailability is low and variable, owing to excessive first pass metabolism. Moreover, it is rapidly eliminated from the body. Therefore, current investigations are focused on development of drug delivery systems suitable for topical melatonin application on mucosa and skin, with the aim to enhance its pharmacokinetic properties and optimize its systemic or local effect. The aim of this study was to prepare nanoparticles for topical melatonin delivery, with sufficient melatonin entrapment and prolonged release. In their preparation, lecithin (>94% phosphatidylcholine), cationic lipid dimethyldioctadecylammonium bromide (DDAB) and sodium alginate were used. Lipid/alginate nanoparticles were prepared by ionic interaction between negatively charged alginate and positively charged lipid mixture of lecithin and DDAB. With the aim to optimize the properties of nanoparticles, the weight ratios of DDAB and sodium alginate to lecithin were varied. Lecithin nanoparticles prepared with lecithin S100 were characterized by negative zeta-potential (-5.0±2.7 mV) and mean diameter of 72.1±0.2 nm. The addition of cationic lipid DDAB in weight ratio to lecithin of 0.5:50 resulted in the formation of positively charged nanoparticles. Lipid-alginate nanoparticles were characterized by negative zeta-potential ranging between -0.2±1.4 and -30.6±1.0 mV, and mean diameter in range of 108.3±1.5 - 295.0±5.4 nm. Nanoparticle size and zeta-potential were influenced by DDAB and alginate to lecithin weight ratios. Lipid-alginate nanoparticles prepared with DDAB to lecithin weight ratio of 0.7:50, 1:50, 3:50 and 5:50, and lecithin to alginate weight ratio of 50:5, were selected for the entrapment of melatonin. The selected nanoparticles were characterized by the zeta-potential < -16 mV. Melatonin entrapment efficiency ranged between 23.8 and 32.1%. The highest entrapment efficiency was observed for the nanoparticles prepared with the highest DDAB to lecithin weight ratio (5:50), that resulted in melatonin concentration within the suspension of nanoparticles of 129.7±4.7 g/ml. Lipid/alginate nanoparticles were characterized by prolonged melatonin release. |
