Proučevanje sestave, metod izdelave in lastnosti liposomov za vnos učinkovin v pljuča

Tasič, Jaka (avtor), Kocbek, Petra (mentor)

Liposomi so nanodostavni sistem, ki je zelo aktualen za vnos učinkovin v pljuča, saj je biokompatibilen in omogoča podaljšano delovanje učinkovin tako lokalno kot sistemsko, z dodatno možnostjo ciljanega delovanja. Namen magistrske naloge je bil, na podlagi sistematičnega pregleda literature, proučiti tehnologije izdelave liposomov ter njihove lastnosti, ugotoviti kako na liposome in njihovo stabilnost vpliva pretvorba v suho obliko ter preveriti ali z liposomi izboljšamo terapevtsko učinkovitost. Z uporabo ustreznega iskalnega niza smo v podatkovni bazi PubMed dobili 238 zadetkov med leti 2012 in 2023 ter med njimi, z uporabo ustreznih vključitveno-izključitvenih kriterijev, 32 ustreznih znanstvenih člankov, ki smo jih podrobno proučili. Ugotovili smo, da so raziskovalci v liposome vgrajevali različne učinkovine, največ za zdravljenje pljučnih infekcij. Prevladujoča metoda izdelave liposomov je bila metoda tankih filmov, izmed organskih topil, ki so jih uporabili za pripravo lipidnega filma, pa so najpogosteje uporabili kloroform. Učinkovine so v liposome pogosteje vgrajevali pasivno. V primeru aktivnega vgrajevanja pa so se skoraj vedno poslužili metode gradienta pH. Ugotovili smo, da uporaba aktivnega vgrajevanja močno izboljša učinkovitost vgrajevanja hidrofilnih učinkovin. V večini raziskav so liposome po izdelavi poenotili z vidika velikosti in slojnosti ter zmanjšali njihovo velikost. Pri tem je bila metoda ekstruzije skozi polikarbonatne membrane veliko učinkovitejša od soniciranja. Za izboljšanje stabilnost liposomov, še posebej pri sobnih pogojih, je bila pretvorba v suho obliko zelo učinkovita. Disperzije liposomov so pretvorili v praškasto obliko z liofilizacijo ali s sušenjem z razprševanjem. Za zaščito formulacije med zamrzovanjem in sušenjem ter za izboljšanje lastnosti produkta sušenja so uporabljali enostavne sladkorje ali aminokisline. V in vivo študijah so, z eno izjemo, formulacije liposomov bile učinkovitejše in varnejše ter imele tudi daljši čas zadrževanja učinkovin v pljučih v primerjavi z raztopino učinkovine oziroma praškom za inhaliranje s prosto učinkovino. Iz tega lahko zaključimo, da so liposomi za dostavo učinkovin v pljuča zelo obetavni dostavni sistem za doseganje prirejenega sproščanja oziroma ciljanega delovanja učinkovin v pljučih, še posebej če jih uporabimo v obliki praškov za inhaliranje in je njihova površina modificirana z vezanimi ligandi za ciljano dostavo. Za večji obseg prihoda liposomskih formulacij na trg pa so potrebne še nadaljnje predklinične in klinične raziskave.

• Jezik: Slovenski jezik
• Ključne besede: ciljana dostava, liposomi, praški za inhaliranje, tehnologija izdelave, vnos v pljuča
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2023
• PID: 20.500.12556/RUL-151775
• Datum objave v RUL: 20.10.2023

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Investigation of composition, preparation methods and properties of liposomes for pulmonary drug delivery

Izvleček

Liposomes are nanodelivery systems, that are intensively studied for pulmonary drug delivery, because they are biocompatible and allow sustained action of drugs for local or systemic treatment with the possibility of targeted delivery. The purpose of this master thesis was a systematic review of literature to investigate preparation methods of liposomes and their properties, find out if drying liposomal dispersion improves stability or affect liposome integrity and to examine if liposomal formulations improve therapeutic efficacy. With the use of appropriate search profile in PubMed database we received 238 results between years 2012 and 2023. We applied inclusion-exclusion criteria and obtained 32 suitable scientific articles, which we examined in detail. We found out, that the most used model drugs were drugs for treating different lung infections. The most used method for liposome preparations was thin film method. Among the used organic solvents, the most common one was chloroform. Greater number of drugs were loaded into liposomes by passive loading. When active loading was used, researchers usually used the pH gradient method. We noticed that using the active loading method firmly improves encapsulation efficacy of hydrophilic drugs. In most researches, liposomes were homogenized to unify their size and lamellarity and to reduce their size. Using extrusion was more efficient than. For improving liposomal stability, especially at room temperature, conversion of liposomal dispersions into liposomal dry powders is highly recommended. Liposomes were converted to powder formulation using lyophilisation or spray drying. Excipients used for protection of liposomes during freeze drying and spray drying and for improving properties of formed dry powders were mostly mono- or disaccharides and amino acids. In in vivo studies, all but one liposomal formulation, were more efficient, safer and had prolonged effect of drugs compared to free drug formulations. We concluded that liposomes for pulmonary drug delivery are very promising drug delivery system to achieve sustained drug release or targeted delivery in lungs, especially if used as liposomal dry powders for inhalation and have a surface modification with targeting ligands. More liposomal medicines for pulmonary delivery are expected to get approved on marked, but more preclinical and clinical studies are demanded first.

• Ključne besede: liposomes, powders for inhalation, pulmonary drug delivery, targeted drug delivery, technology of preparation