Lipid-alginate nanoparticles for dexamethasone nasal delivery

Nazalna primjena lijekova prvi je izbor u liječenju akutnih i kroničnih bolesti sluznice nosa poput rinitisa i rinosinusitisa bez ili sa polipima. Učinkovitost nazalno primijenjenog lijeka ovisi o fiziologiji nosne sluznice te fizičko-kemijskim svojstvima lijeka i ljekovitog pripravka. Suvremena istraživanja usmjerena su na razvoj inovativnih nanosustava koji osiguravaju dulje vrijeme zadržavanja lijeka na nosnoj sluznici i poboljšavaju farmakokinetički profil čime se poboljšava učinkovitost i sigurnost njihove nazalne primjene. Cilj ovog rada bio je pripraviti lipidno-alginatne nanočestice s deksametazonom, odrediti im fizičko-kemijska svojstva te ispitati biokompatibilnost in vitro. Pri ispitivanju biokompatibilnosti, kao modelne epitelne stanice korištene su epitelne stanice karcinoma debelog crijeva (Caco-2 stanice). Lipidno-alginatne nanočestice uspješno su pripravljene ionskom interakcijom anionskog polimera alginata i pozitivno nabijene smjese lipida (lecitina i kationskog lipida dimetil-dioktadecil-amonij bromida (DDAB)). Pripravljene su nanočestice s različitim udjelom DDAB. Veličina lipidno-alginatnih nanočestica s deksametazonom kretala se od 109,1 do 258,6 nm, a površinski naboj od -14,2 do -31,7 mV. Za sve pripravljene nanočestice, uspješnost uklapanja deksametazona bila je veća od 50 %. Uklapanje deksametazona nije značajnije utjecalo na veličinu niti na površinski naboj nanočestica. Sve nanočestice karakterizirane su produljenim oslobađanjem deksametazona. Među razvijenim nanočesticama, najbolja fizičko-kemijska svojstva imale su nanočestice s najvećim udjelom DDAB (lecitin:DDAB 10:1) karakterizirane su najvećim uklapanjem deksametazona (uspješnost uklapanja iznosila je 63,8 %, a sadržaj deksametazona u suspenziji nanočestica 255 ± 7 μg/ml), najnegativnijim zeta potencijalom (-31,7 mV), odgovarajućim srednjim promjerom (252,3 nm) te najmanjim indeksom polidisperznosti (0,241). Biokompatibilnost nanočestica s deksametazonom ispitana je praćenjem metaboličke aktivnosti Caco-2 stanica nakon dvosatnog izlaganja suspenzijama nanočestica različitih koncentracija (50, 100, 200, 400 μg/ml). Vijabilnost Caco-2 stanica nije se značajnije promijenila nakon izlaganja suspenzijama nanočestica u ispitivanom rasponu koncentracija i trajanju, čime je pokazan potencijal lipidno-alginatnih nanočestica za sigurnu nazalnu primjenu deksametazona.Nasal administration of drugs is the first choice in the treatment of acute and chronic nasal mucosa disorders such as rhinitis and rhinosinusitis with or without polyps. The efficacy of nasally administered drugs is dependent on the physiology of the nasal mucosa and the physiochemical properties of the drug and formulation. Current research is focused on the development of innovative drug delivery nanosystems which ensure prolonged residence time at the nasal mucosa and improve the pharmacokinetic profile, thereby improving efficiency and safety of nasal drug administration. The aim of this work was to prepare dexamethasone-loaded lipid/alginate nanoparticles, determine their physiochemical properties and biocompatibility in vitro. In biocompatibility studies, Caco-2 cell line, originally derived from a colon carcinoma, were used as the model epithelial cells. Lipid/alginate nanoparticles were successfully prepared by ionic interaction between anionic polymer alginate and positively charged lipid mixture (lecithin and cationic lipid dimethyl-dioctadecyl-ammonium bromide (DDAB)). Nanoparticles with different amounts of DDAB were prepared. The size of dexamethasone-loaded lipid/alginate nanoparticles was in range from 109.1 to 258.6 nm, and the surface charge was from -14.2 to -31.7 mV. For all prepared nanoparticles, dexamethasone entrapment efficiency was higher than 50 %. Entrapment of dexamethasone did not significantly affect the size or the surface charge of nanoparticles. All nanoparticles were characterized by prolonged dexamethasone release. Among the developed nanoparticles, nanoparticles with the highest amount of DDAB (lecithin: DDAB 10:1) had the best physiochemical properties: they were characterized by the highest entrapment of dexamethasone (entrapment efficacy was 63.8 %, and the content of dexamethasone in the suspension of nanoparticles 255 ± 7 μg/ml), the most negative zeta potential (-31.7 mV), the appropriate size (252.3 nm) and the lowest polydispersity index (0.241). The biocompatibility of nanoparticles was determined by monitoring the metabolic activity of Caco-2 cells after a two-hour exposure to different concentrations of nanoparticle suspensions (50, 100, 200, 400 μg/ml). The viability of Caco-2 cells was not significantly changed after exposure to suspensions of nanoparticles in the tested concentration range and duration, which demonstrates their potential for safe nasal administration of dexamethasone

Ontleding des menschelyken lichaams

Bibliotheek Anatomisch Museu

Plate from Bidloo, 1685 (First Figure)

Originally published in Anatomia humani corporis, centum et quinque tabulis...ad vivum delineates. Amstelodami, Joannes a Sumpt Someren, etc., 1685.These images were taken while preparing a book (Wombs with a View, Springer, 2016) on the history of the illustrations and how they contributed to our understanding of anatomy and physiology of pregnancy, thereby enabling advances in the practice of obstetrics and gynecology

Plate from Bidloo, 1685 (Third Figure)

Originally published in Anatomia humani corporis, centum et quinque tabulis...ad vivum delineates. Amstelodami, Joannes a Sumpt Someren, etc., 1685.These images were taken while preparing a book (Wombs with a View, Springer, 2016) on the history of the illustrations and how they contributed to our understanding of anatomy and physiology of pregnancy, thereby enabling advances in the practice of obstetrics and gynecology

Plate from Bidloo, 1685 (Fourth Figure)

Originally published in Anatomia humani corporis, centum et quinque tabulis...ad vivum delineates. Amstelodami, Joannes a Sumpt Someren, etc., 1685.These images were taken while preparing a book (Wombs with a View, Springer, 2016) on the history of the illustrations and how they contributed to our understanding of anatomy and physiology of pregnancy, thereby enabling advances in the practice of obstetrics and gynecology

Plate from Bidloo, 1685 (Second Figure)

Originally published in Anatomia humani corporis, centum et quinque tabulis...ad vivum delineates. Amstelodami, Joannes a Sumpt Someren, etc., 1685.These images were taken while preparing a book (Wombs with a View, Springer, 2016) on the history of the illustrations and how they contributed to our understanding of anatomy and physiology of pregnancy, thereby enabling advances in the practice of obstetrics and gynecology