Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance
Dermal delivery of tacrolimus - comparative formulation and preclinical evaluation of microemulsions, nanoemulsions and nanostructured lipid carriers as novel carriers for poorly water- soluble drugs
dc.contributor.advisor | Savić, Snežana | |
dc.contributor.other | Pantelić, Ivana | |
dc.contributor.other | Cekić, Nebojša | |
dc.creator | Savić, Vedrana | |
dc.date.accessioned | 2021-12-16T11:49:45Z | |
dc.date.available | 2021-12-16T11:49:45Z | |
dc.date.issued | 2021-06-17 | |
dc.identifier.uri | http://eteze.bg.ac.rs/application/showtheses?thesesId=8413 | |
dc.identifier.uri | https://fedorabg.bg.ac.rs/fedora/get/o:24645/bdef:Content/download | |
dc.identifier.uri | http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48734473 | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/18775 | |
dc.description.abstract | dermatitisa. Danas je na tržištu registrovan samo jedan farmaceutski oblik sa takrolimusom za primenu na koži - mast. Zbog nepoželjnih karakteristika masti (masna tekstura, teško razmazivanje, sporo upijanje, teško spiranje) i težnje da se poboljša njegova isporuka u kožu, sve je veća potreba za razvojem novih, naprednih nosača sa takrolimusom, kao što su mikroemulzije, nanoemulzije i lipidne nanočestice. Usled njihove kompleksnosti, razvoj ovih nosača je dugotrajan i neizvestan proces. Stoga je cilj ove doktorske disertacije bio formulisanje mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica stabilizovanih lecitinom, kao nosača za dermalnu isporuku takrolimusa. Perspektivni nosači su podvrgnuti sveobuhvatnoj fizičkohemijskoj karakterizaciji i studiji stabilnosti, a dermalna isporuka takrolimusa upoređena je sa referentnom mašću. Formulaciona istraživanja omogućila su skupljanje znanja o kritičnim formulacionim i procesnim parametarima za dobijanje stabilnih nosača sa takrolimusom. U dvočasovnoj in vitro studiji penetracije takrolimusa u kožu uha svinje korišćenjem metode sa trakama, uočeno je da su razvijeni nosači superiorniji u poređenju sa referentnom mašću i omogućavaju bolju isporuku takrolimusa u stratum corneum. Takrolimus je u značajnoj meri penetrirao u folikule dlaka, što dodatno može da osigura bolju dermalnu isporuku. Ipak, rezultati 24-časovne in vitro studije permeacije kroz kožu uha svinje pune debljine korišćenjem Franz-ovih difuzionih ćelija ukazuju na bolju permeaciju takrolimusa iz mikroemulzije i referentne masti u poređenju sa nanostrukturiranim lipidnim česticama i nanoemulzijom, što može ukazivati i na mogućnost ispoljavanja sistemskih neželjenih efekata. Generalno, rezultati ukazuju na veliki potencijal dobijenih nosača za dermalnu isporuku takrolimusa, što bi trebalo potvrditi odgovarajućim kliničkim eksperimentalnim postavkama. | sr |
dc.description.abstract | Tacrolimus is a potent immunosuppressive macrolide which is topically used for treatment of atopic dermatitis. Today, there is only one pharmaceutical form for topical application of tacrolimus - tacrolimus ointment. Due to the undesirable characteristics of ointments (greasy texture, difficulty of applying and spreading onto the skin, difficulty to wash them off) and desirable enhancement in dermal delivery, there is an emerging need for development of novel carriers for tacrolimus, such as microemulsions, nanoemulsions and lipid nanoparticles. Owing to their complexity, the development of these carriers can be a long-lasting and uncertain process. Therefore, the aim of this doctoral thesis was to formulate lecithin based microemulsions, nanoemulsions and nanostructured lipid carriers as novel carriers for dermal delivery of tacrolimus. The physicochemical characteristics and stability of promising carriers was assessed, and dermal delivery of tacrolimus was compared to the referent ointment. The formulation evaluation acquired important knowledge about the critical parameters for obtaining stabile carriers with tacrolimus. Results of in vitro penetration of tacrolimus in porcine ear skin suggested superiority of the developed carriers compared to the referent ointment. Additionally, the delivery of tacrolimus into the hair follicles was increased as well, which could provide better dermal delivery of tacrolimus. On the other hand, the results of 24-hour in vitro permeation study using Franz diffusion cells and full thickness porcine ear skin indicated better permeation of tacrolimus from the microemulsion and the referent ointment compared to the nanostructured lipid carrier and the nanoemulsion, which can also suggest a risk of systemic adverse effects by their usage. Overall, the developed carriers could be suggested as promising carriers for dermal delivery of tacrolimus, which should be confirmed by appropriate clinical evaluation. | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Београду, Фармацеутски факултет | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/34031/RS// | |
dc.rights | openAccess | en |
dc.source | Универзитет у Београду | sr |
dc.subject | mikroemulzije | sr |
dc.subject | microemulsions | en |
dc.subject | nanoemulsions | en |
dc.subject | nanostructured lipid carriers | en |
dc.subject | tacrolimus | en |
dc.subject | dermal drug delivery | en |
dc.subject | nanoemulzije | sr |
dc.subject | nanostrukturirane lipidne čestice | sr |
dc.subject | takrolimus | sr |
dc.subject | dermalna isporuka lekova | sr |
dc.title | Dermalna isporuka takrolimusa - uporedna formulaciona i preklinička istraživanja mikroemulzija, nanoemulzija i nanostrukturiranih lipidnih čestica kao naprednih nosača za slabo rastvorne lekovite supstance | sr |
dc.title.alternative | Dermal delivery of tacrolimus - comparative formulation and preclinical evaluation of microemulsions, nanoemulsions and nanostructured lipid carriers as novel carriers for poorly water- soluble drugs | en |
dc.type | doctoralThesis | |
dc.rights.license | ARR | |
dcterms.abstract | Савић, Снежана; Цекић, Небојша; Пантелић, Ивана; Савић, Ведрана; Дермална испорука такролимуса - упоредна формулациона и преклиничка истраживања микроемулзија, наноемулзија и наноструктурираних липидних честица као напредних носача за слабо растворне лековите супстанце; Дермална испорука такролимуса - упоредна формулациона и преклиничка истраживања микроемулзија, наноемулзија и наноструктурираних липидних честица као напредних носача за слабо растворне лековите супстанце; | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/78033/Referat_Savic.pdf | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/78034/Disertacija_11869.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_18775 |