Avtor/Urednik		Mlinšek, Gregor; Kristl, Julijana
Naslov		Vnos peptidnih in proteinskih učinkovin skozi nosno služnico
Prevedeni naslov		Intranasal delivery of peptide and protein drugs
Tip		članek
Vir		Farm Vestn
Vol. in št.		Letnik 51, št. 2
Leto izdaje		2000
Obseg		str. 251-61
Jezik		slo
Abstrakt		As a result of the recombinant DNA technology a high number of peptides and proteins become available to therapy of various diseases. As they show low oral bioavailability new routes for their delivery are under investigation. The intranasal administration which is a very promissing one is described. Absorptive and enzymatic barriers hinder the absorption of peptides and proteins which therefore show low absorption and bioavailability (1-2%). The barriers are overcome by the use of enzyme inhibitors, peptide and protein modifications and by moucosal permeability enhancers such as bile acids, dihydrofuzidates and cyclodextrines. Although some absorption enhancers prove to be highly effective they are also associated with high level of toxicity. They are therefore less suitable for long tenn use. Alternatively, bioadhesive materials that slow the clearance of the applied substances from the nasal mucosa can be used. Apart from physiological barrier immunological barrier becomes important in the chronic use and can lead to ineffective therapy. The unwanted immunologycal effects can be also used in the development of vaccines for local and systemic immunity. Many infectious diseases of respiratory tract are not satisfactorily controlled by the use of parenteral vaccines or these are even not availlable. Protection against these diseases or at least their milder course correlates well with the local immunity induced by locally applied antigen in proper pharmaceutical formulations that are described.
Izvleček		Rezultat razvoja rekombinantne DNA tehnologije je veliko število peptidov in proteinov, namenjenih za zdravljenje različnih bolezni. Zaradi nizke peroralne biološke uporabnosti iščejo nove načine dajanja. Vnos skozi nosno sluznico, ki je zelo obetajoč pristop, je natančneje opisan v predstavljenem članku. Tako absorpcijske kot encimske bariere otežujejo absorpcijo učinkovin, ki imajo zato nizko biološko uporabnost (1-2%). Za izboljšanje prehodnosti se poslužujejo encimskih inhibitorjev, modifikacij peptidov oziroma proteinov ali pa uporabljajo spojine, ki povečajo permeabilnost (*olčne soli, dihidrofuzidati, ciklodekstrini). Kljub temu, da so nekateri pospeševalci absorpcije zelo uspešni, so zaradi toksičnosti za kronično zdravljenje manj primerni, kar omejuje njihovo uporabnost. Altrnativni pristop je v uporabi bioadhezivnih materialov, ki upočasnijo odstranjevanje aplicirane učinkovine z mesta absorpcije. Poleg fizioloških barier se pri intranazalni aplikaciji srečujemo tudi z imunološko bariero, ki pride do izraza pri kronični uporabi učinkovine in lahko vodi v neučinkovito zdravljenje. Neželjeni imunološki učinek pa lahko s pridom uporabimo pri razvoju cepiv za lokalno ali celo sistemsko obrambo. Kar nekaj bolezni respiratornega trakta slabo obvladamo s parenteralnimi cepivi ali pa le-te niso na voljo. Študije dokazujejo, da zaščita ali vsaj blažja oblika bolezni in hitrejše okrevanje najbolje korelira z inducirano lokalno imunostjo. Le-to pa najbolje stimuliramo prav z lokalno apliciranim antigenom v ustreznih farmacevtskih oblikah, ki so natančneje predstavljene.
Deskriptorji		ADMINISTRATION, INTRANASAL PEPTIDES PROTEINS NASAL MUCOSA ABSORPTION LIPOSOMES INSULIN