1816894 Nurin Aqilah Assignment 1

MECHANISM RELEASE OF PACA
Intracellular drug release from the nanoparticles (NP) occurs either by drug diffusing
out from the NP or NP degradation (Sulheim et al., 2016). The drug release also can be induced
by several external factors such as hyperthermia, ultrasound, changes in microenvironment
(e.g.: pH) (cited in Sulheim et al., 2016). A study (cited in Mura et al., 2019), PACA
nanospheres major accumulated at Kupffer cells at the liver and has low uptake at endothelial
and parenchymal cells.
Cited in Mura et al., (2019), a study of nanoparticles uptake by the Kupffer cells was
consistent in in vitro experiments that had been carried out on macrophage and fibroblasts.
Endocytosis, a process of engulfing materials from outside into cells ((Biology Online, 2021)
played a major role in the nanoparticles uptake process (Mura et al., 2019). Once endocytosed,
PACA nanospheres located within lysosomes; membrane-bound organelles that involve in
cellular waste recycling, cellular signalling and energy metabolism, (Bonam et al., 2019). Then,
bioerosion process with the presence of esterase enzyme occurred in this cellular compartment
and marking its biodegradation process (Mura et al., 2019). During this process, the polymer’s
hydrocarbon chain remains unaffected but the enzymatic cleavage of the ester groups from
esterase induced the solubilisation of the resulting PACA polymer (Mura et al., 2019) into
water-soluble poly(cyanoacrylic acid) and a primary alcohol (from the ester hydrolysis)
(Sulheim et al., 2016). Thus, leading to nanoparticles decomposition into phagolysosomes
(cited in Mura et al., 2019).
The uptake of PACA NPs depends on the monomer material and the cell type (Sulheim
et al., 2016). Different cell lines can lead to the different internationalisation pathaways
(Sulheim et al., 2016). Thus choosing monomer from the PACA family is really important in
releasing drug’s rate (Sulheim et al., 2016).
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