Author/Editor		Cegnar, Mateja; Kristl, Julijana
Title		Dostavni sistemi nanometrskih velikosti za vnos proteinov in genov
Translated title		Nanosized drug delivery systems for proteins and genes
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 44, št. 4
Publication year		2005
Volume		str. 447-62
Language		slo
Abstract		This article reviews most systems and approaches for delivery of protein drugs and therapeutic genes into the body. Issues in drug delivery are becoming more important as more potent and specific drugs become available, with knowledge about diseases available from the human genome project. To achieve optimal therapeutic efficacy, drug delivery systems should be customized and very innovative. Novel systems are often nanosized, prepared with the use of specific excipients, and they also have multifaceted advantages in drug delivery. These systems in general can be used to provide targeted (cellular/tissue) delivery of drugs, to improve oral bioavailability, to sustain drug/gene effect at target place, and to improve the stability of therapeutics agents against enzymatic degradation, especially of protein, peptide and nucleic acid drugs. Vectors for gene delivery can be divided into two major groups: viral and nonviral. Due to several limitations of viral vectors, nonviral vectors attract more attention; they consist of a carrier with cationic character that is able to associate with the negatively charged DNA molecule. Formation of this complex protects DNA against denaturation and enables its entry into cells. For specific processes that must take place, such as cell recognition, endocytosolic trafficking, endosomal escape, dissociation of the complex, efficient nuclear uptake and gene expression, several specific molecules are attached to gene delivery devices enabling targeting, fusion with the membrane and changes in the microenvironment, or other ways of affecting cellular function for successful transgenic expression. Combinations of viral and nonviral components are hybrid vectors, which are safer than viral vectors and more efficient than nonviral ones.
Summary		V prispevku predstavljamo sisteme in možnosti vnosa proteinskih učinkovin in genov v telo. Dostavljanje učinkovin na mesto delovanja postaja vse bolj pomembno, saj so se z odkritjem genoma in s tem povezanim znanjem o gensko zasnovanih boleznih pojavile učinkovitejše in zelo specifične učinkovine. Novi sistemi so povečini nanometrskih velikosti (nanodelci, liposomi, nanokompleksi), zgrajeni iz določenih nosilnih snovi, in imajo širok spekter prednosti. Omogočijo ciljanje v tkivo/celico, povečajo biološko uporabnost učinkovine, ji podaljšajo delovanje na ciljnem mestu ter nudijo zaščito pred encimsko razgradnjo, še posebej proteinom in nukleinskim kislinam. Vektorji za vnos genskega materiala v celico so virusni in nevirusni. Zaradi velikih pomanjkljivosti virusnih vektorjev postajajo zanimivejši nevirusni vektorji, ki vključujejo nosilec s kationskim značajem, kar omogoča povezovanje z negativno nabito molekulo DNK. Tvorba kompleksov pomeni zaščito genskega materiala in olajša vnos v celico. Za vodenje procesov v celici, kot so endocitoza, izstop iz lizosoma, razpad kompleksa, vstop v jedro in vključevanje v jedrno DNK, pripnejo na nosilni sistem specifične molekule, ki povečajo ciljanje, zlitje z membranami, spremenijo mikrookolje v celici ali drugače vplivajo na celične funkcije, ki olajšajo vnos genskega materiala v jedro. S kombiniranjem virusnih in nevirusnih vektorjev so razvili hibridne vektorje, ki so varnejši od virusnih in učinkovitejši od nevirusnih.
Descriptors		DRUG DELIVERY SYSTEMS RECOMBINANT PROTEINS GENE THERAPY MICROCHEMISTRY