| Abstract | Cilj istraživanja
Cilj istraživanja je pregledno opisati raspoložive topikalne pripravke u terapiji psorija-ze, raspraviti probleme adherencije pacijenata pri primjeni takvih pripravaka te predstaviti prednosti i nedostatke novih aktivnih tvari i njihovih nosača koji imaju značajan klinički poten-cijal u liječenja psorijaze.
Hipoteze:
1. Razvoj novih aktivnih tvari i/ili nosača s ciljanim učinkom unaprijedit će ishod topikalnog liječenja psorijaze i smanjit će učestalost nuspojava povezanih s dugotrajnom primjenom kortikosteroida.
2. Pravilan izbor topikalnog farmaceutskog oblika i podloge značajan je za osiguravanje dje-lotvornosti aktivne tvari, primjerenih senzornih svojstava i adherencije pacijenata.
Materijal i metode
Literatura je pretraživana prema temi istraživanja, predmetu istraživanja, autorima i časopisu. Pretraživanje je provedeno od općih prema specijaliziranim člancima pri čemu su odabrani članci relevantni za problematiku ovoga specijalističkog rada. Relevantni članci su proučavani na analitički i kritički način s obzirom na definiranje znanstvenog i/ili stručnog problema, istraživanje postojećih znanja o definiranom problemu (literaturni navodi), obliko-vanje radne hipoteze, odabir metoda za ispitivanje hipoteze, prikaz i analizu rezultata te iz-vedene zaključke.
Pri proučavanju relevantnih članaka izdvojeni su najvažniji rezultati, rasprave i zak-ljučci koji su prikazani ovim specijalističkim radom. Pretraživanjem PubMed baze podataka znanstvene literature dat je pregled najnovijih saznanja o patofiziologiji nastanka psorijaze te je načinjen pregledni prikaz topikalnih pripravka za liječenje psorijaze od samih početaka do najnovijih istraživanja za koje se tek očekuje da će postati sastavni dio kliničke prakse.
Rezultati
Približno 80 % pacijenata s psorijazom ima blagi do umjereni oblik bolesti te se liječi topikalnim pripravcima. Lokalna terapija psorijaze obuhvaća niz topikalnih pripravaka koji imaju različitu djelotvornost i sigurnost primjene te se preporučuju u različitim fazama bolesti. Među takve pripravke ubrajaju se pripravci glukokortikoida, analozi vitamina D te njihove kombinacije koje predstavljaju prvi izbor u topikalnoj terapiji psorijaze. Derivati vitamina A također pokazuju obećavajuću učinkovitost dok katran, ditranol, inhibitori kalcineurina, emoli-jentni i keratolitični pripravci imaju sekundarnu ulogu i rijetko se primjenjuju kao prva linija liječenja zbog upitne učinkovitosti i/ili nepoželjnih nuspojava.
Posljednjih godina se razvijaju brojni novi topikalni pripravci s ciljem povećanja učin-kovitosti terapije i postizanja brzog i dugotrajnijeg rezultata liječenja psorijaze. Razvoj novih topikalnih pripravaka se odvija u dva smjera. Napretkom u razumijevanju imunopatogeneze same bolesti otkrivaju se nove terapijske mete i razvija se ciljana terapija. Najbolji primjer su male molekule, unutarstanični modulatori (inhibitori Janus kinaza i fosfodiesteraza) koji spr-ječavaju razvoj i širenja upale u stanici. Alternativa novoj terapiji su novi farmaceutski oblici kao i suvremeni prikladni nanosustavi dostave već postojećih lijekova koji bi postigli kontroli-ranu i lokaliziranu dostavu lijeka, osigurali poboljšanu penetraciju i posljedično doveli do bo-ljeg terapijskog ishoda i povećane adherencije pacijenata.
Zaključak
S napretkom u razumijevanju patogeneze psorijaze razvijaju se nove molekule koje bi osigurale ciljanu terapiju s boljim sigurnosnim profilom i povećanom učinkovitošću. Početni re-zultati se čine obećavajućima, ali postoji potreba za dugotrajnijim kliničkim ispitivanjima i uspo-rednima analizama koje bi pokazale superiornost novih molekula u odnosu na već postojeće komercijalno dostupne pripravke.
Razvoj novih farmaceutskih oblika i suvremenih nanosustava dostave već postojećih lijekova predstavlja obećavajuću metodu unaprjeđenja ishoda topikalnog liječenja psorijaze. Suvremeni topikalni farmaceutski oblici bez okluzivnih osobina osim što povećavaju zadovolj-stvo i adherenciju pacijenata zbog svojih povoljnih kozmetičkih svojstava također osiguravaju brzu i povećanu dostavu lijeka na ciljano mjesto u koži te se sve češće pojavljuju u svakodnev-noj praksi.
Suvremeni nanosustavi dostave tradicionalnih lijekova iako u pretkliničkim istraživanjima pokazuju obećavajuće rezultate ciljane i kontrolirane dostave djelatne tvari, povećane bioraspo-loživosti i smanjenja nuspojava, zahtjevaju brojna klinička ispitivanja kojima bi se dokazala nji-hovu učinkovitost u praksi. |
| Abstract (english) | Objectives
The aim of this research is to define in detail available topical preparations for the treat-ment of psoriasis, discuss the problems of patients' adherence through the time of application and to present the advantages and disadvantages of new active substances and its vehicles, which have important clinical potential in therapy of psoriasis.
Hypotheses are as follows:
1. Development of new active substances and/or vehicles with targeted effect will improve the outcome of topical therapy of psoriasias and will reduce the frequency of side effects related with longterm use of corticosteroids.
2. The right choice of topical pharmaceutical preparation and vehicle is significant to provide efficacy of active substance, appropriate sensory characteristics, and patients' adherence.
Material and methods
The literature search was performed by topic of research, case studies, the authors and the journal. The search is conducted from general to more specialized articles which are selec-ted according to relevance of this work.
Relevant articles are studied analytically and critically with regard to the definition of the scienti-fic and /or technical problems, the research of existing knowledge on a defined problem (citati-ons), design working hypotheses, choice of methods for testing hypotheses, display and analysis of the results and conclusions drawn.
Throughout the research the most important results, discussions and conclusions are selected and presented in this work. Literature search was based on the PubMed scientific da-tabase search and provided an overview of the newest findings of pathogenesis of psoriasis and a review of topical preparations used in therapy from the very beginnings to the latest re-sarch which are still expected to become an integral part of clinical practice.
Results
Approximately 80% of psoriasis patients have mild to moderate forms of disease and are treated with topical preparations. Local therapy of psoriasis includes a number of topical preparations that have different efficacy and safety, and are recommended in different stages of the disease. Among those preparations, formulations of glucocorticoids, vitamin D analogues, and their combinations can be find, and they represent first-line treatment in topical therapy of psoriasis. Vitamin A derivatives also exhibit promising efficacy while tar, dithranol, calcineurin inhibitors, keratolytics and emollients have a secondary role and are rarely used as first-line treatment because of questionable efficacy and / or undesirable side effects.
In recent years, a wide range of efforts has been made to develop new topical agents in order to increase the effectiveness of therapy and to achieve rapid and long-term results of pso-riasis therapy. The development of new topical preparations goes in two directions. New thera-peutic targets and targeted therapy develop in step with progress in understanding of the patho-genesis of psoriasis. The best example are small molecules, intracellular modulators (Janus kinase and phosphodiesterase inhibitors) that prevent development of infection in the psoriatic cell. Alternative to this new treatment are new formulations and novel drug delivery systems of existing drugs that achieve controlled and localized drug delivery, ensure improved penetration and consequently lead to better treatment outcomes and increased patients' adherence.
Conclusion
With the advancement in understanding of the pathogenesis of psoriasis, novel thera-peutics which selectively target disease-defining pathogenic pathway with a better safety profile and increased efficiency are in development. The initial results seem promising, but there is need for long-term clinical trials and head-to-head studies with currently available topical thera-pies to adress potential superiority of these new agents.
The development of new formulations and novel drug delivery systems of existing drugs is a promising method of improving therapeutic outcomes in topical treatment of psoriasis. Mo-dern topical formulations without occlusive properties not only increase satisfaction and adhe-rence of patients due to its favorable cosmetic profile, but also provide increased drug delivery to the target site in the skin and appear routinely in daily practice.
Novel drug delivery systems of exhisting drugs although show promising results in targe-ted and controlled drug delivery to the skin, increased bioavailability and decreased side effects in preclinical studies, require a number of clinical trials which will provide their efficiecy in daily practice. |
