1816894 Nurin Aqilah Assignment 1

SCH 4636
DRUG DELIVERY AND APPLICATION
POLY(ALKYL CYANOACRYLATE)
(PACA) NANOCAPSULES AS NANO
RESERVOIR IN DRUG DELIVERY
SYSTEM
STUDENTS’ NAME
MATRIC NO. : 1816894
LECTURER’S
NAME
: NURIN AQILAH BINTI MOHD ARSHAD
: ASSOC. PROF. DR. WAN KHARTINI BINTI WAN
ABDUL KHODIR
SESSION : SEMESTER 1, 2021/2022
DATE OF
SUBMISSION
: DECEMBER 3, 2021

TABLE OF CONTENT
CONTENT
Graphical Abstract
PAGE
iii
Introduction 1
Functional Design of Poly(alkyl cyanoacrylate) (PACA) as nanocapsules 2
Mechanism release of polyalkylcyaniacrylate (PACA) 3
Conclusion 4
References
iv
ii

GRAPHICAL OVERVIEW
Nanoparticle
Nanosphere
Nanocapsule
Matrix System
Reservoir System
Poly(alkyl cyanoacrylate)
(PACA) capsule
Functional Design
Oil-containing nanocapsules
Water-containing nanocapsules
Poor hydrosoluble drugs
Hydrosoluble drugs
Mechanism of Release
iii

INTRODUCTION
Nanoparticle is submicronic colloidal systems with average diameter ranges from 1 to
200nm (Mura et al., 2019) and usually in spherical shape, and knowing as “nanospheres” or
“nanocapsules” (Mura et al., 2019). Nanospheres usually makes drug adsorbed or dispersed
onto their surface as they are matrix system meanwhile nanocapsules have drug in liquid cavity
reservoir surrounded by polymeric shell and they are vesicular system (Mura et al., 2019). In
this assignment, nanocapsules will be focusing on. In nanocapsules, the water-containing or
oil-containing core has shown as the limiting factor to load the drug inside (Mura et al., 2019).
Thus, the properties of the drugs need to be determined first for drug encapsulation, so that the
drug remains intact in the nanocapsules and the carrier does not degraded before reaching the
target site.
Poly(alkyl cyanoacrylate) (PACA) is one of the functional polymer that has been used
as a nanocapsule for many types of drugs (cited in ). PACA nanoparticles (NP) are also the
promising carriers to across blood-brain barrier (cited in Sulheim et al., 2016) and to cells
located in solid tumours (cited in Sulheim et al., 2016). In this assignment, the functional design
of the PACA polymer as the nanocapsules and the mechanism of PACA nanocapsules release
will be focusing on.
1

FUNCTIONAL DESIGN OF PACA
In article by Vauthier et al., (2007), the authors mentioned that PACA nanoparticles has
versatile properties and compatibility with many pharmaceutical applications, and can cargo
many types of drugs. Almost all kind of drugs with different types of molecules such as
sparingly soluble compounds (e.g.: Indomethacin drug), small water-soluble compounds (e.g.:
nucleoside tri phosphates; antiviral drug), the sophisticated drugs of peptides (e.g.: insulin) and
oligonucleotides (e.g.: Antisense Anti EWS Fli 1; anticancer drug), have shown success
association with the PACA nanoparticles (cited in Vauthier et al., 2007) The two latter
sophisticated drugs are more considered in nanocapsules than nanospheres (Vauthier et al.,
2007).
The encapsulation of these types of molecules greatly depends on the solubility of the
nanocapsules core materials, such as, poor hydrosoluble compounds in oil-containing
nanocapsules, and hydrosoluble compounds in water-containing nanocapsules (cited in
Vauthier et al., 2007).
However, these rules are not applicable for peptides in oil-containing solutions because
small peptide (such as glutathione) could not be encapsulated in the system, but big peptide
(such as insulin) could be retain in the oil droplets of the nanocapsules core during the
surrounding polymer wall rapid formation (cited in Vauthier et al., 2007). Molecular weight
play important role (cited in Vauthier et al., 2007). Due to the rapid polymerisation of
alkylcyanoacrylate at the oil droplets surface, the big peptide are limited from diffusing out to
the aqueous phase, thus noting the drug efficiency entrapment and remains biologically active
after the encapsulation (cited in Vauthier et al., 2007). Not only that, ethanol used in preparing
nanocapsules seemed to prevent side reaction between monomer and peptide’s risk (cited in
Vauthier et al., 2007).
Water-containing nanocapsules are designed with diameters ranging from 250 to 350
nm (cited in Mura et al., 2019) to encapsulate hydrophilic molecules such as oligonucleotides
and small interfering RNA (cited in Mura et al., 2019). The nucleic acids internal localisation
induced better protection against nucleases enzyme compared to the PACA nanospheric simple
adsorption (Mura et al., 2019). The encapsulation of nucleoside was achieved by polycations
coencapsulation that forming ion pair with phosphate nucleosides (cited in Mura et al., 2019).
2

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).
3

CONCLUSION
In conclusion, nanoparticle is submicronic colloidal systems ranges from 1 to 200 nm
and has two types which are nanospheres and nanocapsules. Nanospheres use the matrix system
while nanocapsule use reservoir system. Focusing on the reservoir system, encapsulation of the
drugs depends on the solubility of the core materials, poor hydrosoluble compounds in oilcontaining
nanocapsules, and hydrosoluble compounds in water-containing nanocapsules.
Other than core solubility, the molecular weight of the drugs also play important role in
designing the suitable drug in the chosen polymer. The drugs that are loaded into the
nanocapsules depend on the polymer core’s solubility. The encapsulation of poor hydrosoluble
compounds will be in oil-containing nanocapsules, and hydrosoluble compounds in watercontaining
nanocapsules. The rules may be changed based on the drug’s molecular weight.
Poly(alkyl cyanoacrylate) (PACA) is one of the functional polymer that has been used as a
nanocapsule for many types of drugs and its ability to across blood-brain barrier and to cell in
solid tumour make it one of the unique polymer that is being studied until now.
4

REFERENCES
Biology Online. (2021, July 23). Endocytosis. Biology Articles, Tutorials & Dictionary Online.
Retrieved December 3, 2021, from
https://www.biologyonline.com/dictionary/endocytosis.
Bonam, S. R., Wang, F., & Muller, S. (2019). Lysosomes as a therapeutic target. Nature
Reviews Drug Discovery, 18(12), 923–948. https://doi.org/10.1038/s41573-019-0036-1
Mura, S., Fattal, E., & Nicolas, J. (2019). From poly(alkyl cyanoacrylate) to squalene as core
material for the design of nanomedicines. Journal of Drug Targeting, 27(5-6), 470–501.
https://doi.org/10.1080/1061186x.2019.1579822
Sulheim, E., Baghirov, H., von Haartman, E., Bøe, A., Åslund, A. K., Mørch, Y., & Davies, C.
de. (2016). Cellular uptake and intracellular degradation of poly(alkyl cyanoacrylate)
nanoparticles. Journal of Nanobiotechnology, 14(1). https://doi.org/10.1186/s12951-
015-0156-7
Vauthier, C., Labarre, D., & Ponchel, G. (2007). Design aspects of Poly(alkylcyanoacrylate)
nanoparticles for drug delivery. Journal of Drug Targeting, 15(10), 641–663.
https://doi.org/10.1080/10611860701603372
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