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8 PEGylated Nanocarriers forGene Therapy
tion of advanced therapy medicinal products. EMBO Mol Med 9(6):737–740. https://doi.
org/10.15252/emmm.201707573
An HJ etal (2020) Sarcopenia in autoimmune and rheumatic diseases: a comprehensive review. Int
J Mol Sci 21(16):5678. https://doi.org/10.3390/ijms21165678
Anguela XM, High KA (2019) Entering the modern era of gene therapy. Annu Rev Med
70:273–288. https://doi.org/10.1146/annurev- med- 012017- 043332
Bade BC, Dela Cruz CS (2020) Lung Cancer 2020: epidemiology, etiology, and prevention. Clin
Chest Med 41(1):1–24. https://doi.org/10.1016/j.ccm.2019.10.001
Barbara R etal (2017) Novel Curcumin loaded nanoparticles engineered for blood-brain barrier
crossing and able to disrupt Abeta aggregates. Int J Pharm 526(1–2):413–424. https://doi.
org/10.1016/j.ijpharm.2017.05.015
Beheshti SA etal (2022) CAR Treg: a new approach in the treatment of autoimmune diseases. Int
Immunopharmacol 102:108409. https://doi.org/10.1016/j.intimp.2021.108409
Bottai G etal (2017) Progress in nonviral gene therapy for breast cancer and what comes next?
Expert Opin Biol Ther 17(5):595–611. https://doi.org/10.1080/14712598.2017.1305351
Boulaiz H etal (2005) Non-viral and viral vectors for gene therapy. Cell Mol Biol (Noisy-le-grand)
51(1):3–22
Braden AM, Stankowski RV, Engel JM, Onitilo AA etal (2014) Breast cancer biomarkers: risk
assessment, diagnosis, prognosis, prediction of treatment efcacy and toxicity, and recurrence.
Curr Pharm Des 20(30):4879–4898. https://doi.org/10.2174/1381612819666131125145517
Bruun J etal (2015) Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA
to blood-brain barrier and glioma cells. Int J Nanomedicine 10:5995–6008. https://doi.
org/10.2147/ijn.S87334
Cagel M etal (2017) Polymeric mixed micelles as nanomedicines: achievements and perspectives.
Eur J Pharm Biopharm 113:211–228. https://doi.org/10.1016/j.ejpb.2016.12.019
Cao Y et al (2019) Recent advances in chitosan-based carriers for gene delivery. Mar Drugs
17(6):381. https://doi.org/10.3390/md17060381
Chakravarty D, Solit DB (2021) Clinical cancer genomic proling. Nat Rev Genet 22(8):483–501.
https://doi.org/10.1038/s41576- 021- 00338- 8
Chang CZ etal (2015) Curcumin, encapsulated in nano-sized PLGA, down-regulates nuclear fac-
tor κB (p65) and subarachnoid hemorrhage induced early brain injury in a rat model. Brain Res
1608:215–224. https://doi.org/10.1016/j.brainres.2015.02.039
Chen J etal (2016) Production and clinical development of nanoparticles for gene delivery. Mol
Ther Methods Clin Dev 3:16023. https://doi.org/10.1038/mtm.2016.23
Chen Y etal (2018) In vitro evaluation of anti-aggregation and degradation behavior of PEGylated
polymeric nanogels under in vivo like conditions. Macromol Biosci 18(1). https://doi.
org/10.1002/mabi.201700127
Chopra A (2004) Pegylated bis(4-(N-(2-naphthyl)phenylamino)phenyl)-fumaronitrile (NPAPF)
nanoparticles. In: Molecular imaging and contrast agent database (MICAD). National Center
for Biotechnology Information (US), Bethesda
Cristallini C etal (2016) Micro- and macrostructured PLGA/gelatin scaffolds promote early car-
diogenic commitment of human mesenchymal stem cells invitro. Stem Cells Int 2016:7176154.
https://doi.org/10.1155/2016/7176154
Dart A (2022) Cancer’s sensory experience. Nat Rev Cancer 22(8):433. https://doi.org/10.1038/
s41568- 022- 00492- z
Dastjerd NT etal (2022) Gene therapy: a promising approach for breast cancer treatment. Cell
Biochem Funct 40(1):28–48. https://doi.org/10.1002/cbf.3676
Davis PB, Cooper MJ (2007) Vectors for airway gene delivery. AAPS J 9(1):E11–E17. https://doi.
org/10.1208/aapsj0901002
de Souza Guimaraes M et al (2022) PEG-grafted liposomes for L-asparaginase encapsulation.
Pharmaceutics 14(9):1819. https://doi.org/10.3390/pharmaceutics14091819
Delogu LG etal (2009) Conjugation of antisense oligonucleotides to PEGylated carbon nanotubes
enables efcient knockdown of PTPN22in T lymphocytes. Bioconjug Chem 20(3):427–431.
https://doi.org/10.1021/bc800540j
267
268
Demirgoz D, Garg A, Kokkoli E (2008) PR_b-targeted PEGylated liposomes for prostate cancer
therapy. Langmuir 24(23):13518–13524. https://doi.org/10.1021/la801961r
Edis Z etal (2021) Nanocarriers-mediated drug delivery systems for anticancer agents: an overview
and perspectives. Int J Nanomedicine 16:1313–1330. https://doi.org/10.2147/IJN.S289443
Fazil M etal (2012) Nanotherapeutics for Alzheimer’s disease (AD): past, present and future. J
Drug Target 20(2):97–113. https://doi.org/10.3109/1061186x.2011.607499
Formiga FR et al (2010) Sustained release of VEGF through PLGA microparticles improves
vasculogenesis and tissue remodeling in an acute myocardial ischemia-reperfusion model. J
Control Release 147(1):30–37. https://doi.org/10.1016/j.jconrel.2010.07.097
Fornaguera C etal (2015a) PLGA nanoparticles prepared by nano-emulsion templating using low-
energy methods as efcient nanocarriers for drug delivery across the blood-brain barrier. J
Control Release 211:134–143. https://doi.org/10.1016/j.jconrel.2015.06.002
Fornaguera C etal (2015b) Galantamine-loaded PLGA nanoparticles, from nano-emulsion tem-
plating, as novel advanced drug delivery systems to treat neurodegenerative diseases. Nanoscale
7(28):12076–12084. https://doi.org/10.1039/c5nr03474d
Fredman G etal (2015) Targeted nanoparticles containing the proresolving peptide Ac2-26 protect
against advanced atherosclerosis in hypercholesterolemic mice. Sci Transl Med 7(275):275ra20.
https://doi.org/10.1126/scitranslmed.aaa1065
Gabizon A, Shmeeda H, Barenholz Y (2003) Pharmacokinetics of pegylated liposomal doxoru-
bicin: review of animal and human studies. Clin Pharmacokinet 42(5):419–436. https://doi.
org/10.2165/00003088- 200342050- 00002
Gajbhiye KR etal (2020) PEGylated nanocarriers: a promising tool for targeted delivery to the brain.
Colloids Surf B Biointerfaces 187:110770. https://doi.org/10.1016/j.colsurfb.2019.110770
Ganesan P etal (2015) Recent trends in the development of nanophytobioactive compounds and
delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease mod-
els. Int J Nanomedicine 10:6757–6772. https://doi.org/10.2147/ijn.S93918
Gao Y, Li LB, Zhai G (2008) Preparation and characterization of Pluronic/TPGS mixed micelles
for solubilization of camptothecin. Colloids Surf B Biointerfaces 64(2):194–199. https://doi.
org/10.1016/j.colsurfb.2008.01.021
Gao H etal (2013) The impact of PEGylation patterns on the invivo biodistribution of mixed shell
micelles. Int J Nanomedicine 8:4229–4246. https://doi.org/10.2147/IJN.S51566
Geiger BC etal (2018) Cartilage-penetrating nanocarriers improve delivery and efcacy of growth
factor treatment of osteoarthritis. Sci Transl Med 10(469):eaat8800. https://doi.org/10.1126/
scitranslmed.aat8800
Giamas G (2020) Cancer gene therapy: vision and strategy for the new decade. Cancer Gene Ther
27(3–4):115. https://doi.org/10.1038/s41417- 020- 0169- 8
Giamas G, Gagliano T (2022) Cancer gene therapy 2020: highlights from a challenging year.
Cancer Gene Ther 29(1):1–3. https://doi.org/10.1038/s41417- 021- 00340- 6
Giannavola C et al (2003) Inuence of preparation conditions on acyclovir-loaded poly-d,l-
lactic acid nanospheres and effect of PEG coating on ocular drug bioavailability. Pharm Res
20(4):584–590. https://doi.org/10.1023/a:1023290514575
Ginn SL et al (2018) Gene therapy clinical trials worldwide to 2017: an update. J Gene Med
20(5):e3015. https://doi.org/10.1002/jgm.3015
Godin B et al (2010) Emerging applications of nanomedicine for the diagnosis and treatment
of cardiovascular diseases. Trends Pharmacol Sci 31(5):199–205. https://doi.org/10.1016/j.
tips.2010.01.003
Goncalves GAR, Paiva RMA (2017) Gene therapy: advances, challenges and perspectives.
Einstein (Sao Paulo) 15(3):369–375. https://doi.org/10.1590/S1679- 45082017RB4024
Gregori M, Masserini M, Mancini S (2015) Nanomedicine for the treatment of Alzheimer’s dis-
ease. Nanomedicine (Lond) 10(7):1203–1218. https://doi.org/10.2217/nnm.14.206
Gu W etal (2013) Nanotechnology in the targeted drug delivery for bone diseases and bone regen-
eration. Int J Nanomedicine 8:2305–2317. https://doi.org/10.2147/ijn.S44393
Gupta P etal (2015) Quercetin conjugated poly(beta-amino esters) nanogels for the treatment of cel-
lular oxidative stress. Acta Biomater 27:194–204. https://doi.org/10.1016/j.actbio.2015.08.039
L. Mishra et al.
8 PEGylated Nanocarriers forGene Therapy
Hamidi M, Azadi A, Raei P (2006) Pharmacokinetic consequences of pegylation. Drug Deliv
13(6):399–409. https://doi.org/10.1080/10717540600814402
Hofheinz RD et al (2005) Liposomal encapsulated anti-cancer drugs. Anti-Cancer Drugs
16(7):691–707. https://doi.org/10.1097/01.cad.0000167902.53039.5a
Hua S etal (2015) Advances in oral nano-delivery systems for colon targeted drug delivery in
inammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomedicine
11(5):1117–1132. https://doi.org/10.1016/j.nano.2015.02.018
Ikoba U etal (2015) Nanocarriers in therapy of infectious and inammatory diseases. Nanoscale
7(10):4291–4305. https://doi.org/10.1039/c4nr07682f
Iwata H et al (2009) Local delivery of synthetic prostacycline agonist augments collateral
growth and improves cardiac function in a swine chronic cardiac ischemia model. Life Sci
85(5–6):255–261. https://doi.org/10.1016/j.lfs.2009.06.002
Jain NK, Nahar M (2010) PEGylated nanocarriers for systemic delivery. Methods Mol Biol
624:221–234. https://doi.org/10.1007/978- 1- 60761- 609- 2_15
Järvinen K, Järvinen T, Urtti A (1995) Ocular absorption following topical delivery. Adv Drug
Deliv Rev 16(1):3–19
Jo DH etal (2015) Size, surface charge, and shape determine therapeutic effects of nanoparti-
cles on brain and retinal diseases. Nanomedicine 11(7):1603–1611. https://doi.org/10.1016/j.
nano.2015.04.015
Karakoti AS et al (2011) PEGylated inorganic nanoparticles. Angew Chem Int Ed Engl
50(9):1980–1994. https://doi.org/10.1002/anie.201002969
Katare DP, Aeri V (2010) Progress in gene therapy: a review. IJTPR 1(33):e41
Khalid MN et al (2006) Long circulating poly(ethylene glycol)-decorated lipid nanocap-
sules deliver docetaxel to solid tumors. Pharm Res 23(4):752–758. https://doi.org/10.1007/
s11095- 006- 9662- 5
Klibanov AL etal (1990) Amphipathic polyethyleneglycols effectively prolong the circulation
time of liposomes. FEBS Lett 268(1):235–237. https://doi.org/10.1016/0014- 5793(90)81016- h
Koide H etal (2009) Elucidation of accelerated blood clearance phenomenon caused by repeat
injection of PEGylated nanocarriers. Yakugaku Zasshi 129(12):1445–1451. https://doi.
org/10.1248/yakushi.129.1445
Koudelka S etal (2016) Liposomal nanocarriers for plasminogen activators. J Control Release
227:45–57. https://doi.org/10.1016/j.jconrel.2016.02.019
Laginha KM et al (2005) Determination of doxorubicin levels in whole tumor and tumor
nuclei in murine breast cancer tumors. Clin Cancer Res 11(19 Pt 1):6944–6949. https://doi.
org/10.1158/1078- 0432.CCR- 05- 0343
Lara-Guerra H, Roth JA (2016) Gene therapy for lung cancer. Crit Rev Oncog 21(1–2):115–124.
https://doi.org/10.1615/CritRevOncog.2016016084
Lautenschläger C et al (2013) PEG-functionalized microparticles selectively target inamed
mucosa in inammatory bowel disease. Eur J Pharm Biopharm 85(3 Pt A):578–586. https://
doi.org/10.1016/j.ejpb.2013.09.016
Leung PS et al (2010) Gene therapy in autoimmune diseases: challenges and opportunities.
Autoimmun Rev 9(3):170–174. https://doi.org/10.1016/j.autrev.2009.10.004
Li SD, Huang L (2010) Stealth nanoparticles: high density but sheddable PEG is a key for tumor
targeting. J Control Release 145(3):178–181. https://doi.org/10.1016/j.jconrel.2010.03.016
Lim JA etal (2019) Development of the clinical assessment scale in autoimmune encephalitis. Ann
Neurol 85(3):352–358. https://doi.org/10.1002/ana.25421
Liu L etal (2022) PEGylation effectively improves anti-breast cancer efciency of heat shock pro-
tein gp96 inhibitory polypeptide. Sheng Wu Gong Cheng Xue Bao 38(9):3363–3378. https://
doi.org/10.13345/j.cjb.220067
Lloyd-Jones D et al (2010) Heart disease and stroke statistics—2010 update: a report from
the American Heart Association. Circulation 121(7):e46–e215. https://doi.org/10.1161/
circulationaha.109.192667
Lu X, Zhang K (2018) PEGylation of therapeutic oligonucletides: from linear to highly branched
PEG architectures. Nano Res 11(10):5519–5534. https://doi.org/10.1007/s12274- 018- 2131- 8
269
270
Lukasiewicz S et al (2021) Polycaprolactone nanoparticles as promising candidates for nano-
carriers in novel nanomedicines. Pharmaceutics 13(2):191. https://doi.org/10.3390/
pharmaceutics13020191
Ma F, Laster K, Dong Z (2022) The comparison of cancer gene mutation frequencies in
Chinese and U.S. patient populations. Nat Commun 13(1):5651. https://doi.org/10.1038/
s41467- 022- 33351- 4
Matoba T, Egashira K (2011) Anti-inammatory gene therapy for cardiovascular disease. Curr
Gene Ther 11(6):442–446. https://doi.org/10.2174/156652311798192888
Matsumura Y et al (2004) Phase I clinical trial and pharmacokinetic evaluation of NK911, a
micelle-encapsulated doxorubicin. Br J Cancer 91(10):1775–1781. https://doi.org/10.1038/
sj.bjc.6602204
Mattheolabakis G etal (2009) In vivo investigation of tolerance and antitumor activity of cisplatin-
loaded PLGA-mPEG nanoparticles. Eur J Pharm Biopharm 71(2):190–195. https://doi.
org/10.1016/j.ejpb.2008.09.011
Mehrabian A et al (2022) Preparation, characterization, and biodistribution of glutathione
PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach.
Iran J Basic Med Sci 25(3):302–312. https://doi.org/10.22038/ijbms.2022.60306.13369
Miyamoto D etal (2008) Completely dispersible PEGylated gold nanoparticles under physiologi-
cal conditions: modication of gold nanoparticles with precisely controlled PEG-b-polyamine.
Langmuir 24(9):5010–5017. https://doi.org/10.1021/la703813f
Mohamed M etal (2019) PEGylated liposomes: immunological responses. Sci Technol Adv Mater
20(1):710–724. https://doi.org/10.1080/14686996.2019.1627174
Mu L, Elbayoumi TA, Torchilin VP (2005) Mixed micelles made of poly(ethylene glycol)-phos-
phatidylethanolamine conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate
as pharmaceutical nanocarriers for camptothecin. Int J Pharm 306(1–2):142–149. https://doi.
org/10.1016/j.ijpharm.2005.08.026
Mun EA et al (2014) On the barrier properties of the cornea: a microscopy study of the pen-
etration of uorescently labeled nanoparticles, polymers, and sodium uorescein. Mol Pharm
11(10):3556–3564. https://doi.org/10.1021/mp500332m
Muralidharan P etal (2014) Inhalable PEGylated phospholipid nanocarriers and PEGylated thera-
peutics for respiratory delivery as aerosolized colloidal dispersions and dry powder inhalers.
Pharmaceutics 6(2):333–353. https://doi.org/10.3390/pharmaceutics6020333
Nair J etal (2020) Translatable gene therapy for lung cancer using Crispr CAS9—an exploratory
review. Cancer Gene Ther 27(3–4):116–124. https://doi.org/10.1038/s41417- 019- 0116- 8
Nakamura T etal (2010) Large payloads of gold nanoparticles into the polyamine network core
of stimuli-responsive PEGylated nanogels for selective and noninvasive cancer photothermal
therapy. Nanoscale 2(5):739–746. https://doi.org/10.1039/b9nr00329k
Nakano Y etal (2016) Nanoparticle-mediated delivery of Irbesartan induces cardioprotection from
myocardial ischemia-reperfusion injury by antagonizing monocyte-mediated inammation.
Sci Rep 6:29601. https://doi.org/10.1038/srep29601
Nakki S etal (2015) Improved stability and biocompatibility of nanostructured silicon drug car-
rier for intravenous administration. Acta Biomater 13:207–215. https://doi.org/10.1016/j.
actbio.2014.11.019
Nasim F, Sabath BF, Eapen GA (2019) Lung cancer. Med Clin North Am 103(3):463–473. https://
doi.org/10.1016/j.mcna.2018.12.006
Nayerossadat N, Maedeh T, Ali PA (2012) Viral and nonviral delivery systems for gene delivery.
Adv Biomed Res 1:27. https://doi.org/10.4103/2277- 9175.98152
Nissinen T etal (2016) Tailored dual PEGylation of inorganic porous nanocarriers for extremely
long blood circulation in vivo. ACS Appl Mater Interfaces 8(48):32723–32731. https://doi.
org/10.1021/acsami.6b12481
Otani K et al (2019) Colon cancer with perforation. Surg Today 49(1):15–20. https://doi.
org/10.1007/s00595- 018- 1661- 8
L. Mishra et al.
8 PEGylated Nanocarriers forGene Therapy
Padin-Gonzalez E etal (2022) Understanding the role and impact of poly (ethylene glycol) (PEG)
on nanoparticle formulation: implications for COVID-19 vaccines. Front Bioeng Biotechnol
10:882363. https://doi.org/10.3389/fbioe.2022.882363
Pascual-Gil S etal (2017) Cytokine-loaded PLGA and PEG-PLGA microparticles showed similar
heart regeneration in a rat myocardial infarction model. Int J Pharm 523(2):531–533. https://
doi.org/10.1016/j.ijpharm.2016.11.022
Pawlik TM (2018) Colon cancer. Surg Oncol Clin N Am 27(2):xiii–xiv. https://doi.org/10.1016/j.
soc.2017.11.013
Pishavar E etal (2020) Cholesterol-conjugated PEGylated PAMAM as an efcient nanocarrier for
plasmid encoding interleukin-12 immunogene delivery toward colon cancer cells. Biotechnol
Prog 36(3):e2952. https://doi.org/10.1002/btpr.2952
Puras G etal (2011) Encapsulation of Aβ(1-15) in PLGA microparticles enhances serum anti-
body response in mice immunized by subcutaneous and intranasal routes. Eur J Pharm Sci
44(3):200–206. https://doi.org/10.1016/j.ejps.2011.07.010
Ramamoorth M, Narvekar A (2015) Non viral vectors in gene therapy—an overview. J Clin Diagn
Res 9(1):GE01-6. https://doi.org/10.7860/JCDR/2015/10443.5394
Razi Sooyani S et al (2013) Gene therapy, early promises, subsequent problems, and recent
breakthroughs. Adv Pharm Bull 3(2):249–255. https://doi.org/10.5681/apb.2013.041
Ren H etal (2019) Role of liposome size, surface charge, and PEGylation on rheumatoid arthritis
targeting therapy. ACS Appl Mater Interfaces 11(22):20304–20315. https://doi.org/10.1021/
acsami.8b22693
Rittchen S etal (2015) Myelin repair in vivo is increased by targeting oligodendrocyte precur-
sor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF). Biomaterials
56:78–85. https://doi.org/10.1016/j.biomaterials.2015.03.044
Roberts TC, Langer R, Wood MJA (2020) Advances in oligonucleotide drug delivery. Nat Rev
Drug Discov 19(10):673–694. https://doi.org/10.1038/s41573- 020- 0075- 7
Sahu R, Pattanayak SP (2020) Strategic developments & future perspective on gene ther-
apy for breast cancer: role of mTOR and Brk/ PTK6 as molecular targets. Curr Gene Ther
20(4):237–258. https://doi.org/10.2174/1566523220999200731002408
Sanders NN et al (2007) Wanted and unwanted properties of surface PEGylated nucleic
acid nanoparticles in ocular gene transfer. J Control Release 122(3):226–235. https://doi.
org/10.1016/j.jconrel.2007.05.004
Sarparanta M et al (2012) Intravenous delivery of hydrophobin-functionalized porous sili-
con nanoparticles: stability, plasma protein adsorption and biodistribution. Mol Pharm
9(3):654–663. https://doi.org/10.1021/mp200611d
Schopf LR etal (2015) Topical ocular drug delivery to the back of the eye by mucus-penetrating
particles. Transl Vis Sci Technol 4(3):11. https://doi.org/10.1167/tvst.4.3.11
Shahbazi R et al (2023) Design and optimization various formulations of PEGylated niosomal
nanoparticles loaded with phytochemical agents: potential anti-cancer effects against human
lung cancer cells. Pharmacol Rep 75(2):442–455. https://doi.org/10.1007/s43440- 023- 00462- 8
Sharma D et al (2014) Formulation and optimization of polymeric nanoparticles for intranasal
delivery of lorazepam using Box-Behnken design: invitro and invivo evaluation. Biomed Res
Int 2014:156010. https://doi.org/10.1155/2014/156010
Shi J (2015) Regulatory networks between neurotrophins and miRNAs in brain diseases and can-
cers. Acta Pharmacol Sin 36(2):149–157. https://doi.org/10.1038/aps.2014.135
Shiraishi K, Yokoyama M (2019) Toxicity and immunogenicity concerns related to PEGylated-
micelle carrier systems: a review. Sci Technol Adv Mater 20(1):324–336. https://doi.org/1
0.1080/14686996.2019.1590126
Shroff K, Kokkoli E (2012) PEGylated liposomal doxorubicin targeted to alpha5beta1- expressing
MDA-MB-231 breast cancer cells. Langmuir 28(10):4729–4736. https://doi.org/10.1021/
la204466g
Shu SA et al (2015) Gene therapy for autoimmune disease. Clin Rev Allergy Immunol
49(2):163–176. https://doi.org/10.1007/s12016- 014- 8451- x
271
272
Simón-Yarza T etal (2013) Functional benets of PLGA particulates carrying VEGF and CoQ10in
an animal of myocardial ischemia. Int J Pharm 454(2):784–790. https://doi.org/10.1016/j.
ijpharm.2013.04.015
Stone D (2010) Novel viral vector systems for gene therapy. Viruses 2(4):1002–1007. https://doi.
org/10.3390/v2041002
Su S, Kang PM (2020) Recent advances in nanocarrier-assisted therapeutics delivery systems.
Pharmaceutics 12(9):837. https://doi.org/10.3390/pharmaceutics12090837
Suk JS et al (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene
delivery. Adv Drug Deliv Rev 99(Pt A):28–51. https://doi.org/10.1016/j.addr.2015.09.012
Tahara K et al (2011) Oral nuclear factor-κB decoy oligonucleotides delivery system with chi-
tosan modied poly(D,L-lactide-co-glycolide) nanospheres for inammatory bowel disease.
Biomaterials 32(3):870–878. https://doi.org/10.1016/j.biomaterials.2010.09.034
Taher M etal (2023) PEGylated liposomes enhance the effect of cytotoxic drug: a review. Heliyon
9(3):e13823. https://doi.org/10.1016/j.heliyon.2023.e13823
Tamura M etal (2011) In vitro and invivo characteristics of core-shell type nanogel particles: opti-
mization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated
nanogels. Acta Biomater 7(9):3354–3361. https://doi.org/10.1016/j.actbio.2011.05.027
Tang W etal (2019) Emerging blood-brain-barrier-crossing nanotechnology for brain cancer ther-
anostics. Chem Soc Rev 48(11):2967–3014. https://doi.org/10.1039/c8cs00805a
Torchilin VP (2007) Micellar nanocarriers: pharmaceutical perspectives. Pharm Res 24(1):1–16.
https://doi.org/10.1007/s11095- 006- 9132- 0
Tucka J, Bennett M, Littlewood T (2012) Cell death and survival signalling in the cardiovascular
system. Front Biosci (Landmark Ed) 17(1):248–261. https://doi.org/10.2741/3925
van Vlerken LE, Vyas TK, Amiji MM (2007) Poly(ethylene glycol)-modied nanocarriers for
tumor-targeted and intracellular delivery. Pharm Res 24(8):1405–1414. https://doi.org/10.1007/
s11095- 007- 9284- 6
Verhoef JJ, Anchordoquy TJ (2013) Questioning the use of PEGylation for drug delivery. Drug
Deliv Transl Res 3(6):499–503. https://doi.org/10.1007/s13346- 013- 0176- 5
Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug Discov
Today 10(21):1451–1458. https://doi.org/10.1016/S1359- 6446(05)03575- 0
Vijayan VM, Shenoy SJ, Muthu J (2017) Octreotide-conjugated uorescent PEGylated polymeric
nanogel for theranostic applications. Mater Sci Eng C Mater Biol Appl 76:490–500. https://doi.
org/10.1016/j.msec.2017.03.125
Vilella A etal (2015) Endocytosis of nanomedicines: the case of glycopeptide engineered PLGA
nanoparticles. Pharmaceutics 7(2):74–89. https://doi.org/10.3390/pharmaceutics7020074
Vyas SP, Vaidya B (2009) Targeted delivery of thrombolytic agents: role of integrin receptors.
Expert Opin Drug Deliv 6(5):499–508. https://doi.org/10.1517/17425240902878002
Wang YY etal (2008) Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that
“slip” through the human mucus barrier. Angew Chem Int Ed Engl 47(50):9726–9729. https://
doi.org/10.1002/anie.200803526
Wang W etal (2013) Non-viral gene delivery methods. Curr Pharm Biotechnol 14(1):46–60
Wang C et al (2015a) Accelerated blood clearance phenomenon upon cross-administration
of PEGylated nanocarriers in beagle dogs. Int J Nanomedicine 10:3533–3545. https://doi.
org/10.2147/ijn.S82481
Wang F et al (2015b) Efcient RNA delivery by integrin-targeted glutathione responsive poly-
ethyleneimine capped gold nanorods. Acta Biomater 23:136–146. https://doi.org/10.1016/j.
actbio.2015.05.028
Wang L, Wang FS, Gershwin ME (2015c) Human autoimmune diseases: a comprehensive update.
J Intern Med 278(4):369–395. https://doi.org/10.1111/joim.12395
Wang D, Tai PWL, Gao G (2019) Adeno-associated virus vector as a platform for gene therapy
delivery. Nat Rev Drug Discov 18(5):358–378. https://doi.org/10.1038/s41573- 019- 0012- 9
Wang H etal (2022) Mechanisms and challenges of nanocarriers as non-viral vectors of thera-
peutic genes for enhanced pulmonary delivery. J Control Release 352:970–993. https://doi.
org/10.1016/j.jconrel.2022.10.061
L. Mishra et al.
8 PEGylated Nanocarriers forGene Therapy
Wang S etal (2023) Liposomes for tumor targeted therapy: a review. Int J Mol Sci 24(3):2643.
https://doi.org/10.3390/ijms24032643
Werner ME etal (2013) Preclinical evaluation of Genexol-PM, a nanoparticle formulation of pacli-
taxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer. Int J Radiat
Oncol Biol Phys 86(3):463–468. https://doi.org/10.1016/j.ijrobp.2013.02.009
Wójcik P etal (2021) Oxidative stress and lipid mediators modulate immune cell functions in auto-
immune diseases. Int J Mol Sci 22(2):723. https://doi.org/10.3390/ijms22020723
Wonganan P, Croyle MA (2010) PEGylated adenoviruses: from mice to monkeys. Viruses
2(2):468–502. https://doi.org/10.3390/v2020468
Xin H etal (2010) Enhanced anti-glioblastoma efcacy by PTX-loaded PEGylated poly(varepsilon-
caprolactone) nanoparticles: invitro and invivo evaluation. Int J Pharm 402(1–2):238–247.
https://doi.org/10.1016/j.ijpharm.2010.10.005
Xin H et al (2011) Angiopep-conjugated poly(ethylene glycol)-co-poly(epsilon- caprolactone)
nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials
32(18):4293–4305. https://doi.org/10.1016/j.biomaterials.2011.02.044
Xue HY etal (2015) Lipid-based nanocarriers for RNA delivery. Curr Pharm Des 21(22):3140–3147.
https://doi.org/10.2174/1381612821666150531164540
Yang K etal (2015) Biodegradable nanotopography combined with neurotrophic signals enhances
contact guidance and neuronal differentiation of human neural stem cells. Macromol Biosci
15(10):1348–1356. https://doi.org/10.1002/mabi.201500080
Yin W etal (2021) Cancer and stem cells. Exp Biol Med (Maywood) 246(16):1791–1801. https://
doi.org/10.1177/15353702211005390
Zwacka RM, Dunlop MG (1998) Gene therapy for colon cancer. Hematol Oncol Clin North Am
12(3):595–615. https://doi.org/10.1016/s0889- 8588(05)70010- 1
273
PEGylated Nanocarrier System
forNucleic Acid Delivery
AkhileshTiwari, SreeharshaNagaraja, RakeshSahu,
andMuktikaTekade
Abstract
The transport of nucleic acids to host sites must be successful in creating gene
therapy techniques. Due to their capacity to shield nucleic acids from deteriora-
tion and improve their cellular absorption and bioavailability, PEGylated nano-
carrier systems have demonstrated signicant potential as delivery technologies.
This manuscript outlines creating and evaluating a PEGylated nanocarrier sys-
tem for transporting nucleic acids. The nanocarrier comprised a lipid-based core
for encasing nucleic acids and a polyethylene glycol (PEG) coating to increase
stability and decrease immunogenicity. The nanocarrier may effectively encap-
sulate and shield the nucleic acids from nuclease deterioration. Moreover, it dis-
played invitro minimal cytotoxicity and good cellular uptake and transfection
9
A. Tiwari (*)
Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak,
Anuppur, Madhya Pradesh, India
S. Nagaraja
Department of Pharmaceutics, Vidya Siri College of Pharmacy, Bengaluru, Karnataka, India
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal
University, Al-Ahsa, Saudi Arabia
R. Sahu
National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, An
Institute of National Importance, Government of India, Department of Pharmaceuticals,
Ministry of Chemicals and Fertilizers, Palaj, Opp. Air force station, Gandhinagar,
Gujarat, India
M. Tekade
School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshila Campus,
Indore, Madhya Pradesh, India
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
275
276
A. Tiwari et al.
efciency. In vivo tests revealed that considerable gene activation in the liver was
caused by the nanocarrier’s ability to effectively carry nucleic acids to target cells
in a mouse model.
Keywords
PEGylated · Nanocarrier · Nucleic acid delivery
9.1 Introduction
Therapies based on nucleic acids have shown promise in treating various illnesses,
such as cancer, viral infections, and genetic abnormalities. Unfortunately, nucleic
acid treatments have difculty translating into the clinic due to their poor pharmacokinetics, bioavailability, and lack of adequate and secure delivery mechanisms.
Due to their capacity to shield nucleic acids from deterioration, improve cellular
absorption, and enable intracellular transport, nanocarrier systems, such as liposomes, polymeric nanoparticles, and dendrimers, have been intensively explored as
possible delivery vehicles for nucleic acids (Sridharan and Gogtay 2016; Shtykalova
etal. 2023).
The quick removal of nucleic acids from the circulation by the reticuloendothelial system (RES), which restricts their accumulation at the target location, is one of
the main obstacles to developing efcient nanocarrier systems for nucleic acid
delivery. Increased circulation duration has been achieved via polyethylene glycol
(PEG)ylation, which involves the covalent attachment of PEG chains to the surface
of nanocarriers by reducing their recognition by RES cells. PEGylation can also
enhance the stability and biocompatibility of nanocarriers and reduce their toxicity
and immunogenicity.
Attaching PEG to a molecule is known as PEGylation, sometimes known as
polyethylene glycosylation. The pharmaceutical industry frequently employs this
technique to enhance the pharmacokinetic characteristics of medications, including
extending their duration in circulation and lowering their immunogenicity. Many
medications, including interferons, enzymes, and antibodies, have been proven to
be safer and more effective after being PEGylated. The PEG molecule is biocompatible, non-toxic, and non-immunogenic, making it an ideal candidate for drug
modication. One example of a PEGylated drug is Pegasys chronic hepatitis B, and
C are managed with peginterferon alfa-2a. The addition of PEG to interferon alfa-2a
improves its pharmacokinetic properties and allows for less frequent dosing compared to non-PEGylated interferon alfa-2a. Another example is Adagen (pegademase bovine), a PEGylated enzyme used to treat adenosine deaminase deciency.
The PEGylation of the enzyme increases its half-life and reduces its immunogenicity, allowing for a longer-lasting and more effective treatment (Veronese and
Pasut 2005).
PEGylation is a process that joins the polymer PEG strands to molecules,
most often peptides, proteins, and antibody fragments. It can increase the efcacy
and safety of numerous medicines. The physicochemical characteristics, such as