Abstract
The targeted pro-drug is a classical pro-drug design often representing a non-specific chemical approach to mask undesirable drug properties, such as limited bioavailability, lack of site specificity, and chemical instability. On the other hand, targeted pro-drug design represents a new strategy for directed and efficient drug delivery. Quinolone antibiotics exert their pharmacological effect by inhibiting the cell wall synthesis of the pathogen. However, development of resistance exists, which instigates for a new higher congener to remain in clinical practice. To overcome this phenomenon and also to produce site-specific activity of the cell walls of the pathogen, ofloxacin is conjugated with a hydroxypropyl methacrylamide polymer backbone moiety. The results of in vitro release studies indicate the possibilities for the development of a new drug for site-specific therapy with an improved t 1/2 of the drug. This novel pro-drugmay have opened a new vista in antibiotic chemotherapy. .
Ciljani dizajn proleka je klasican dizajn proleka koji predstavlja nespecifican hemijski pristup u cilju maskiranja nezeljenih osobina leka kao sto su ogranicena bioraspolozivost, nedostatak specificnosti i hemijska nestabilnost. S druge strane, ciljani dizajn proleka daje novu strategiju za direktno i efikasno oslobadjanje leka. Hinolinski antibiotici pokazuju farmakoloski efekat inhibiranjem sinteze celijskog zida patogenih mikroorganizama. Ipak, zbog rezistencije koja nastaje istrazuju se srodna jedinjenja koja bi se zadrzala u klinickoj praksi. Radi prevazilazenja ovog fenomena i ostvarivanja specificnog delovanja na celijski zid patogenih celija ofloksacin je konjugovan sa polimerom hidroksipropil-metakrilamida kao nosacem. Rezultati in vitro studije ukazuju na mogucnost razvoja novih lekova specificnog delovanja i poboljsanja bioloskog poluvremena eliminacije leka. Time se otvaraju nove mogucnosti u savremenoj antibiotskoj hemoterapiji. .