Utdrag från senaste artikeln.
When using the fimaporfin (TPCS2a) photosensitizer [51], which is currently being developed in clinical studies [106], the photosensitizer molecule is added as a separate entity, not being chemically
or physically attached to the other components of the delivery system. For many applications it
could however seem advantageous to have the photosensitiser attached to the nucleic acid cargo, the delivery vehicle or both. Such systems have been developed both for oligonucleotides [162,163] and
for plasmid [186] delivery, and has been shown to work well. While there are obvious advantages of having all components in one cargo, it however also makes the synthesis and formulation processes more complicated, and for some covalent systems it may also be a problem to achieve optimal doses
of all components in the system at the same time. Thus, using PCI with small molecule
photosensitizer like fimaporfin constitutes a flexible and efficient system for nucleic acid delivery.
Enkelheten är genial. Amphinex är som ni vet autoklaverbar och kan sedan stå lång tid på en hylla i väntan på användning. Behöver inte administreras samtidigt eller i en och samma komplex som carriern för att fungera vilket underlättar.
Angående leverering mha virus:
However, many viral systems have severe safety concerns, and in general it
would be very advantageous to be able to target virus-mediated gene delivery to the desired sites in the body, and also to use as low doses of virus as possible to diminish production problems, safety concerns and the induction of unwanted immune reactions.
It was therefore somewhat surprising that PCI could strongly enhance adenovirus-mediated transduction, with an enhancement of >20 times achieved by the employment of PCI [204,205]. In the same study dose response experiments showed that the
transduction-enhancing effect of PCI was especially good at low virus doses, something that may be very valuable in the clinical use of adenovirus mediated therapies.
Återigen den stora fördelen med fimaporfin, låg dos ger minskade biverkningar men 20ggr förstärkning.
Kanske är det pga olika bra resultat i olika celltyper som Astra Zeneca ville testa ut i så många olika celltyper som möjligt?
Both for adenoviral and for lipidic delivery vehicles there however seem to by
substantial differences in the PCI effect between different cell types [196,214], indicating differences in endocytic trafficking and the processing of such vehicles in different cell types.
Many polymeric delivery vehicles (e.g., PEI) are believed to effect endosomal escape through a
so-called “proton sponge” effect [215], where protons are captured by the vehicles leading to
endosomal swelling and rupture of the endosomes. For this mechanism to be effective it is necessary with a minimum amount of vehicle inside the endosomes to induce the necessary endosomal
swelling. While this may be easy to achieve in vitro, it is much more difficult in vivo, especially since such vehicles often induce toxic reactions strongly limiting the amount of vehicle that can be injected. It is therefore very interesting that PCI is able to enhance nucleic acid delivery with such vehicles in amounts far below what is needed for the induction of endosomal escape by the “proton sponge” effect [214,216], potentially making it possible to use the vehicles also for in vivo
applications where vehicle toxicity would normally be of concern.
Samma visa igen: mycket lägre doser ger mindre biverkningar men ökad effekt. 
