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152 I. F. Uchegbu
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Fig. 7.5 Schematic diagram showing the oral uptake of GCPQ nanoparticles
reduced toxicity (Lv et al. 2011), although it is not clear if the particles were actually
taken up orally. Paclitaxel has also been delivered in N-(2-phenoxyacetamide)-6-Oglycolchitosan nanoparticles and found to evade the P-glycoprotein efflux pump
when delivered as this polymeric nanoparticle formulation (Soundararajan et al.
2016).
7.4.3 Topical Ocular
The delivery of drugs to the ocular surface requires that drugs enjoy a long enough
residence time to reduce the need for short-dose intervals. Transport of drugs
through the cornea to the aqueous humour and into the conjunctiva and connective
tissue of the eye may also be influenced by the nature of the delivery system.
Prednisolone transport to the aqueous humour, on topical application to the rabbit
model, is significantly enhanced with the use of GCPQ nanoparticles (Qu et al.
2006). GCPQ nanoparticles, we now know, deliver multiple hydrophobic drugs to
and across the ocular tissues on topical ocular administration, increasing ocular
bioavailability by between fivefold and 18-fold, as meas ured by the Cmax
(Fig. 7.6) (Badr et al. 2021, 2022; Uchegbu et al. 2021). In rabbit studies, tacrolimus
deposition in the cornea and conjunctiva is increased by 18-fold and fivefold,
respectively, when applied as GCPQ nanoparticles (Badr et al.
tacrolimus and rapamycin were delivered to the choroid retina on topical ocular
administration to the rabbit model using GCPQ nanoparticles, with rapamycin being
2021). Both
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140
120
100
80
60
microgram dosed
40
20
Cyclosporine A Cmax ng/ g per
0
NOVA22007
(Santen)
Fig. 7.6 Cyclosporine A deposition in the rabbit cornea from various formulations: NOVA22007
(Daull et al. 2013), restasis and NM133 (Uchegbu et al. 2021), cyclasol (Scherer et al. 2013), cequa
(Cholkar et al. 2015). NM133, which comprises GCPQ nanoparticles delivers more drug to the
cornea than all other formulations
Restasis
(Allergan)
Topical Cyclosporine A Formulations
NM133
(Nanomerics)
CyclaSol
(Novaliq)
Cequa
Fig. 7.7 A schematic representation of drug delivery to the front and back of the eye using GCPQ
(molecular envelope technology—MET) nanoparticles
delivered in therapeutic quantities (Badr et al. 2021, 2022). The ability to topically
deliver drugs to the back of the eye would represent a breakthrough if replicated in
humans. A schematic representation of the hypothesised mechanism of ocular
delivery when GCPQ drug-loaded particles are applied to the eye appears in Fig. 7.7.
The improved pharmacodynamic activity of polymer nanoparticle formulations
has been demonstrated with chitosan–hyaluronic acid nanoparticles when applied
topically to the eye and containing dorzolamide hydrochloride or timolol maleate as
these formulat ions reduced intraocular pressure to a greater extent than the marketed
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formulation of the drugs (Wadhwa et al. 2010). Additionally, dexamethasone loaded
into cross-linked poly(N-isopropylacrylamide)-co-poly(vinyl pyrrolidone)-co-poly
(methacrylic acid) micelles to yield dexamethasone polymer nanoparticles showed
better pharmacodynamic activity against uveitis when compared to dexamethasone
solution and this was attributed to the mucoadhesion of the particles (Rafie et al.
2010).
7.4.4 Brain Delivery
7.4.4.1 Intravenous
Delivering drugs to the brain is severely limited by the blood–brain barrier, an
anatomical and physiological barrier composed of the neurovascular unit, efflux
membrane transporters and drug-degrading enzymes (Lalatsa et al.
methods have been developed to overcome this barrier, and polymers have figured
largely as transport vectors. The exploitation of transport pathways on brain endothelial cells has resulted in polymer nanoparticles being transcytosed across brain
endothelial cells (Zensi et al.
include the transporter specific to Apolipoprotein E (Zensi et al. 2009), which, when
conjugated to cross-linked albumin nanoparticles, resulted in particle uptake across
the brain endothelial cells. Exploitation of this transport of polymer particles across
the blood–brain barrier for medicinal benefit was realised when doxorubicin was
delivered to the brain following the intravenous administration of doxorubicin poly
(n-butyl)cyanoacrylate nanoparticles coated with polysorbate 80 (Wohlfart et al.
2011). Coated particles were superior to non-coated particles in delivering doxoru-
bicin to the brain, and this is thought to be due to the polysorbate 80-coated particles’
ability to recruit plasma apolipoprotein E to the particles’ surface and use this ligand
to access transport across the brain endothelial cells via the LRP1 receptor (Kreuter
et al. 2002).
Other mechanisms by which polymer particle delivery across the blood–brain
barrier may be achieved include the conjugation of F3 peptide (CKDEPQRRSAR
LAKPAPPKPEPKPKKAPAKK) to the surface of poly(ethylene glycol)-block-poly
(lactic acid) nanoparticles (Hu et al. 2013). The F3 peptide targets nucleolin, a
transport protein expressed on the surface of glioma cells and the tumour
neovasculature brain endothelial cells. When these F3-decorated nanoparticles
loaded with paclitaxel are administered in tandem with a cell-penetrating peptide
(tLyp-1—CGNKRTR) which targets neuroligin-1, a transmembrane protein over
expressed on tumour vasculature, there is improved survival in animals bearing
intracranial C6 glioma cells (Hu et al. 2013).
The delivery of macromolecules to the brain has been achieved using receptormediated uptake technology, as conjugating the rabies virus glycoprotein (RVG29)
to the surface of a Pluronic-chitosan-based nanocarrier resulted in the delivery of the
2009). The various transporters that have been used
2011). Various
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protein beta-galactosidase to the brain after intravenous administration (Kim et al.
2013).
Although the uptake of polymer nanoparticles by brain endothelial cells is an
attractive concept, the delivery of drugs to the brain may also be accompanied by no
real particle transport across the blood–brain barrier. In the case of GCPQ particles
loaded with leucine
palmitate, leucine
5
-enkephalin (LENK) or a LENK lipidic prodrug tyrosine1-
5
-enkephalin (TPLENK), the particles are not taken up by the
blood–brain barrier (Lalatsa et al. 2012b; Moger et al. 2012). Despite this lack of
particle brain uptake, there is sufficient peptide drug delivery to the brain to elicit an
anti-nociceptive response on intravenous administration of GCPQ nanoparticleencapsulated LENK or TPLENK, whereas intravenous administration of LENK
does not elicit an anti-nociceptive response. The positively charged GCPQ particles
appear to adhere to the luminal side of the brain endothelial cells (Moger et al.
2012),
enabling the particle cargo to achieve close contact with the blood–brain barrier and
the GCPQ particles also prevent peptide degradation within the plasma (Lalatsa et al.
2012b); both mechanisms resulting in the increased delivery of the peptide across the
blood–brain barrier. It is hypothesised that the lipidic prodrug—TPLENK is also
able to diff use more easily across the barrier when compared to the peptide alone,
due to a reduced level of hydrogen bonding of TPLENK with the water in the blood.
7.4.4.2 Nose to Brain
There are no approved particulate formulations indicated for central nervous system
conditions at the present time. All the nanoparticle formulations described above are
at the experimental stage and many of them are at the pre-clinical experimental stage.
The clinical testing of intravenous polymer particles for brain diseases is certainly
not widespread or a growing phenomenon.
The non-invasive nose-to-brain delivery of solution formulations in humans has
been well documented (Chapman et al. 2013). Insulin and oxytocin solutions have
both been administered via the nose-to-brain route and evidence of target engagement observed in humans. There are many instances of pre-clinical studies of the
nose-to-brain route, involving particulates, e.g. olanzapine-PLGA nanoparticles
(Seju et al. 2011), and solution formulations (Wang et al. 2019). These include our
own studies, with particulates encapsulating peptides (Godfrey et al. 2017), small
hydrophobic molecules (Uchegbu et al. 2014), siRNA (Alamoudi et al. 2022) and
genes (Petkova et al. 2022; Fatani et al. 2023).
There are no neuropeptides approved for clinical use. Envelta
®
is a pre-clinical
stage pain therapeutic comprising GCPQ (also known as the Molecular Envelope
Technology—MET) nanoparticles encapsulating LENK (Godfrey et al. 2017). This
therapeutic candidate is a nano-in-micro powder designed to be administered for
pain relief via the nose-to-brain route using a delivery device. The nasal powder
comprises agglomerated nanoparticles, into a 20 μm microparticle, which then
redisperses into nanoparticles and is expected to generate drug-filled nanoparticles
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Fig. 7.8 The delivery of therapeutic nucleic acid polyplexes results in gene expression in the
frontal brain areas on nose-to-brain delivery
within the brain. The formulation shows no analgesic tolerance, no analgesic tolerance in morphine-tolerant animals, no reward-seeking behaviour and is centrally
acting. The centrally acting profile indicates that Envelta
®
will be less likely to cause
significant constipation in humans and the lack of reward-seeking behaviour bodes
well for the ability of this therapeutic candidate to be non-addictive. Virpax Pharmaceuticals is developing Envelta
®
for clinical use.
A recent significant advance has involved the delivery of plasmids to the brain via
the nasal route with the nucleic acids traversing the olfactory bulb to access the
cerebrum (Simao Carlos et al.
2017; Alamoudi et al. 2022; Petkova et al. 2022;
Fatani et al. 2023). Glycol chitosan polyplexes of the luciferase reporter gene, when
delivered via the nose-to-brain route, resulted in protein expression predominantly in
the cerebral cortex (Petkova et al.
2022; Fatani et al. 2023). Protein expression
followed the trend: olfactory bulb ¼ cerebral cortex > striatum > mid-brain ¼ cerebellum (Fig.
7.8) (Fatani et al. 2023).
Gene silencing has also been reported in the olfactory bulb and brain tissue
following the nose-to-brain delivery of siRNA-ITCH delivered as PEG-amine
polyplexes (Alamoudi et al. 2022). These studies open the field for the development
of therapeutic gene therapies to treat intractable neurological conditions such as
neurodegenerative conditions.
7.4.5 Nasal
7.4.5.1 Systemic Nasal Delivery
The nasal route of administration is favoured because of the highly vascularised
nature of the nasal mucosa and the possibility of delivering drug to the brain via the
neuronal routes. As such, nasal formulations of insulin (Dyer et al. 2002) and
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leuprolide (Shahnaz et al. 2012) in chitosan nano particles have been used as a
non-parenteral route for the systemic delivery of such peptides.
7.4.5.2 Delivering to the Nasal Passages
At the start of the COVID-19 pandemic, there was a huge effort expended, aimed at
finding mul tiple ways to mitigate transmission of the virus. The vaccination regimes
that were eventually approved did not halt transmission, even though they did reduce
disease severity (Schaefer et al.
reduce viral replication in cells in vitro, reducing viral titres by 3 log and reducing
viral titres in a three-dimensional culture of the human airway epithelium (Pyrc et al.
2021). In in vivo studies, radiolabelled GCPQ was resident in the nares for up to 24 h
and in in vivo challenge studies with the COVID-19 virus, there was a trend towards
reducing viral load in the brain on pre-treatment with GCPQ nanoparticle dispersions (Pyrc et al.
preventing viral proximity to the ACE-2 receptor and thus inhibiting viral entry into
the nasal epithelial cells. These nanoparticles may serve as a nasal spray prophylactic
to be used against seasonal coronaviruses or the deadly coronaviruses, similar to
those responsible for the COVID-19 pandemic.
2021). It is hypothesised that GCPQ nanoparticles act as a barrier,
2020). Polymeric GCPQ nanoparticles were found to
7.4.6 Subcutaneous
Subcutaneous delivery routes have been used for depot preparations of microparticle
formulations and coarse emulsions. We have solved the problem of needing to
administer a high dose of a cancer drug candidate with poor oral bioavailability by
formulating a subcutaneous dosage form comprising a GCPQ-encapsulated drug
candidate—CUDC 101, in which the nanoparticles are coated with hyaluronidase to
enable a high volume of the nanoparticle dispersion to be delivered via the subcutaneous route (Soundararajan et al. 2020). These hyaluronidase-coated GCPQ—
CUDC 101 nanoparticles prolonged survival by over 200% when compared with the
administration of CUDC 101 with hyaluronidase alone (from 15 to 43 days)
(Soundararajan et al. 2020). Such a formulation could be administered in the home
by the patient and removes the need for the hospital administration of an intravenous
formulation of the drug.
An interesting new glucose-sensitive subcutaneous formulation of insulin has
also been described in which an acid-degradable acetalated-dextran conjugate delivered insulin rapidly when an acyclic acetal group was conjugated to the dextran and
delivered insulin in a more delayed fashion when a cyclic acetal group was conjugated to the dextran (Volpatti et al.
polymeric systems would provide insulin release kinetics approximating the physiological situation.
2020). The authors believe that the use of both
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7.5 Conclusion
Polymer nanoparticles are prepared from amphiphilic polymers, water-insoluble
polymers and even from hydrophilic polymers. They have been demonstrated to
improve the bioavailability of low molecular weight and biologic (e.g. genes) drugs
via the oral, intravenous, intranasal and topical ocular routes. They act by protecting
the drug from degradation, reducing drug clearance and even transporting drugs
across biological barriers while still encapsulated in the nanoparticles. Polymeric
nanoparticles also inhibit viral replication in vitro.
Problems
Question 1 Describe how nanoparticles may be formed from polymers in aqueous
media.
Answer 1 Amphip hilic polymers when dispersed in water or other aqueous
medium spontaneously self-assemble to form nanoparticles. This self-assembly
may be promoted by probe sonication, high-pressure homogenisation or
microfluidisation for example. This is the method used to make polymers from the
chitosan amphiphile: N-monomethyl, NN-dimethyl, N-trimethyl, N-acetyl,
N-palmitoyl, 6-O-glycol chitosan (GCPQ). Hydrophobic polymers such as poly
(lactide-co-glycolide) (PLGA) may be precipitated from an organic solvent emulsified into aqueous media, with the formed nanoparticles stabilised by surfactants
present in the aqueous media, e.g. PLGA nanoparticles formed in the presence of
poly(oxyethylene) 20 sorbitan monooleate. Hydrophilic polymers such as chitosan
may be prepared by using ionic gelation in which a counter anion such as
tripolyphosphate is used to form nanogels with the positively charged chitosan.
Question 2 Give examples of how polymer nanoparticles have been used to
provide a therapeutic benefit either in clinical or pre-clinical settings.
Answer 2 Most polymer nanoparticles have demonstrated their benefits in cancer
chemotherapy. Docetaxel poly(DL-lactic acid)-block-poly(ethylene glycol)
nanoparticles have been evalua ted in prostate cancer patients and found to extend
plasma half-life of the drug; an observation which could lead to better tumour
targeting with the drug. Furthermore, N-monomethyl, NN-dimethyl, N-tri methyl,
N-acetyl, N-palmitoyl, 6-O-glycol chitosan (GCPQ) nanoparticles have been demonstrated to facilitate drug delivery to the choroid retina.
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References
Adams ML, Andes DR, Kwon GS. Amphotericin B encapsulated in micelles based on poly
(ethylene oxide)-block-poly(L-amino acid) derivatives exerts reduced in vitro hemolysis but
maintains potent in vivo antifungal activity. Biomacromolecules. 2003;4(3):750–7.
Alamoudi AA, Mendez PA, Workman D, Schatzlein AG, Uchegbu IF. Brain gene silencing with
cationic amino-capped poly(ethylene glycol) polyplexes. Biomedicines. 2022;10(9):2182.
Alexandridis P, Holzwarth JF, Hatton TA. Micellization of poly(ethylene oxide)-poly(propylene
oxide)- poly(ethylene oxide) triblock copolymers in aqueous-solutions – thermodynamics of
copolymer association. Macromolecules. 1994;27(9):2414–25.
Al-Kulabi A, Gooden L, Uchegbu IF. Nanoparticulate mycophenolic acid eye drops – analytical
validation of a high-performance liquid chromatography assay and stability studies. Pharm
Nanotechnol. 2021;9(2):101 –10.
Badr MY, Abdulrahman NS, Schatzlein AG, Uchegbu IF. A polymeric aqueous tacrolimus
formulation for topical ocular delivery. Int J Pharm. 2021;599:120364.
Badr MY, Halwani AA, Odunze U, Eskandarpour M, Calder VL, Schatzlein AG, Uchegbu IF. The
topical ocular delivery of rapamycin to posterior eye tissues and the suppression of retinal
inflammatory disease. Int J Pharm. 2022;621:121755.
Brown MD, Uchegbu IF, Schatzlein AG. Polyamino acid based polymeric vesicles for gene
delivery. Br J Cancer. 1999;80:P97.
Chapman CD, Frey WH 2nd, Craft S, Danielyan L, Hallschmid M, Schioth HB, Benedict
C. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res. 2013;30
(10):2475–84.
Cheng WP, Gray AI, Tetley L, Hang TLB, Schatzlein AG, Uchegbu IF. Polyelectrolyte
nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds.
Biomacromolecules. 2006;7(5):1509–20.
Cholkar K, Gilger BC, Mitra AK. Topical, aqueous, clear cyclosporine formulation design for
anterior and posterior ocular delivery. Transl Vis Sci Technol. 2015;4(3):1–1.
Chooi KW, Gray AI, Tetley L, Fan YL, Uchegbu IF. The molecular shape of poly(propylenimine)
dendrimers has a profound effect on their self assembly. Langmuir. 2010;26:2301–16.
Chooi KW, Hou XL, Qu X, Soundararajan R, Uchegbu IF. Claw amphiphiles with a dendrimer
core – nanoparticle stability and drug encapsulation is directly proportional to the number of
digits. Langmuir. 2013;29(13):4214–24.
Cortes J, Saura C. Nanoparticle albumin-bound (nab (TM))-paclitaxel: improving efficacy and
tolerability by targeted drug delivery in metastatic breast cancer. EJC Suppl. 2010;8(1):1–10.
Daull P, Lallemand F, Philips B, Lambert G, Buggage R, Garrigue JS. Distribution of cyclosporine
A in ocular tissues after topical administration of cyclosporine A cationic emulsions to
pigmented rabbits. Cornea. 2013;32(3):345–54.
Discher DE, Ahmed F. Polymersomes. Annu Rev Biomed Eng. 2006;8:323–41.
Dufes C, Schatzlein AG, Tetley L, Gray AI, Watson DG, Olivier JC, Couet W, Uchegbu
IF. Niosomes and polymeric chitosan based vesicles bearing transferrin and glucose ligands
for drug targeting. Pharm Res. 2000;17(10):1250–8.
Dyer AM, Hinchcliffe M, Watts P, Castile J, Jabbal-Gill I, Nankervis R, Smith A, Illum L. Nasal
delivery of insulin using novel chitosan based formulations: a comparative study in two animal
models between simple chitosan formulations and chitosan nanoparticles. Pharm Res. 2002;19
(7):998–1008.
Ensign LM, Tang BC, Wang YY, Tse TA, Hoen T, Cone R, Hanes J. Mucus-penetrating
nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci Transl Med.
2012;4(138):138ra79.
Fatani AS, Petkova A, Schatzlein AG, Uchegbu IF. Dose-dependent delivery of genes to the
cerebral cortex via the nasal route. Int J Pharm. 2023;644:123343.
Fisusi FA, Siew A, Chooi KW, Okubanjo O, Garrett N, Lalatsa K, Serrano D, Summers I, Moger J,
Stapleton P, Satchi-Fainaro R, Schatzlein AG, Uchegbu IF. Lomustine nanoparticles enable
160 I. F. Uchegbu
https://t.me/med1917
both bone marrow sparing and high brain drug levels - a strategy for brain cancer treatments.
Pharm Res. 2016;33(5):1289–303.
Fu Q, Sun J, Zhang WP, Sui XF, Yan ZT, He ZG. Nanoparticle albumin-bound (NAB) technology
is a promising method for anti-cancer drug delivery. Recent Pat Anticancer Drug Discov. 2009;4
(3):262–72.
Garrett NL,
Lalatsa A, Uchegbu I, Schatzlein A, Moger J. Exploring uptake mechanisms of oral
nanomedicines using multimodal nonlinear optical microscopy. J Biophotonics. 2012;5(5–6):
458–68.
Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages
of vehicle selection for drug formulation. Eur J Cancer. 2001;37(13):1590–8.
Godfrey L, Iannitelli A, Garrett NL, Moger J, Imbert I, King T, Porreca F, Soundararajan R,
Lalatsa A, Schatzlein AG, Uchegbu IF. Nanoparticulate peptide delivery exclusively to the brain
produces tolerance free analgesia. J Control Release. 2017;270:135–44.
Green MR, Manikhas GM, Orlov S, Afanasyev B, Makhson AM, Bhar P, Hawkins MJ. Abraxane
a novel Cremophor
®
-free, albumin-bound particle form of paclitaxel for the treatment of
advanced non-small-cell lung cancer. Ann Oncol. 2006;17(8):1263–8.
Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021;6
(12):1078–94.
Hrkach J, Von Hoff D, Ali MM, Andrianova E, Auer J, Campbell T, De Witt D, Figa M,
Figueiredo M, Horhota A, Low S, McDonnell K, Peeke E, Retnarajan B, Sabnis A,
Schnipper E, Song JJ, Song YH, Summa J, Tompsett D, Troiano G, Hoven TV, Wright J,
LoRusso P, Kantoff PW, Bander NH, Sweeney C, Farokhzad OC, Langer R, Zale S. Preclinical
development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci Transl Med. 2012;4(128):128ra39.
Hu QY, Gu GZ, Liu ZY, Jiang MY, Kang T, Miao DY, Tu YF, Pang ZQ, Song QX, Yao L, Xia
HM, Chen HZ, Jiang XG, Gao XL, Chen J. F3 peptide-functionalized PEG-PLA nanoparticles
co-administrated with tLyp-1 peptide for anti-glioma drug delivery. Biomaterials. 2013;34(4):
1135–45.
Kataoka K, Matsumoto T, Yokoyama M, Okano T, Sakurai Y, Fukushima S, Okamoto K, Kwon
GS. Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) copolymer
micelles: their pharmaceutical characteristics and biological significance. J Control Release.
2000;64(1–3):143–53.
Kim H, Kim Y, Guk K, Yoo D, Lim H, Kang G, Lee D. Fully biodegradable and cationic poly
(amino oxalate) particles for the treatment of acetaminophen-induced acute liver failure. Int J
Pharm. 2012;434(1–2):243–50.
Kim JY, Choi WI, Kim YH, Tae G. Brain-targeted delivery of protein using chitosan- and RVG
peptide-conjugated, pluronic-based nano-carrier. Biomaterials. 2013;34(4):1170–8.
Kirkpatrick P. Pressures in the pipeline. Nat Rev Drug Discov. 2003;2:337.
Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin
R. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain
barrier. J Drug Target. 2002;10(4):317–25.
Lalatsa A, Schätzlein AG, Uchegbu IF. Drug delivery across the blood brain barrier. In:
MurrayMoo-Young M, Butler M, Webb C, et al., editors. Comprehensive biotechnology. 2nd
ed. Amsterdam: Elsevier; 2011. p. 657–68.
Lalatsa A, Garrett N, Moger J, Schatzlein AG, Davis C, Uchegbu IF. Delivery of peptides to the
blood and brain after oral uptake of quaternary ammonium palmitoyl glycol chitosan
nanoparticles. Mol Pharm. 2012a;9(6):1764–74.
Lalatsa A, Lee V, Malkinson JP, Zloh M, Schatzlein AG, Uchegbu IF. A prodrug nanoparticle
approach for the oral delivery of a hydrophilic peptide, leucine(5)-enkephalin, to the brain. Mol
Pharm. 2012b;9(6):1665–80.
Lalatsa A, Schatzlein AG, Mazza M, Le TB, Uchegbu IF. Amphiphilic poly(l-amino acids) - New
materials for drug delivery. J Control Release. 2012c;161(2):523–36.
®
,
7 Polymeric Nanoparticles 161
https://t.me/med1917
Lalatsa A, Schatzlein AG, Garrett NL, Moger J, Briggs M, Godfrey L, Iannitelli A, Freeman J,
Uchegbu IF. Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and
delivers the peptide to the brain on intravenous administration. J Control Release. 2015;197:
87–96.
Lavasanifar A, Samuel J, Kwon GS. Poly(ethylene oxide)-block-poly(L-amino acid) micelles for
drug delivery. Adv Drug Deliv Rev. 2002;54(2):169–90.
Le TBH, Schatzlein AG, Uchegbu IF. Polymer hydrophobicity has a positive effect on the oral
absorption of cyclosporine A from poly(ethylenimine) based nanomedicines. Pharm
Nanotechnol. 2013;1:15–25.
Lee J, Lee C, Kim TH, Lee ES, Shin BS, Chi SC, Park ES, Lee KC, Youn YS. Self-assembled
glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting antidiabetic inhalation system. J Control Release. 2012;161(3):728–34.
Lee SW, Kim YM, Cho CH, Kim YT, Kim SM, Hur SY, Kim JH, Kim BG, Kim SC, Ryu HS, Kang
SB. An open-label, randomized, parallel, phase II trial to evaluate the efficacy and safety of a
cremophor-free polymeric micelle formulation of paclitaxel as first-line treatment for ovarian
cancer: a Korean Gynecologic Oncology Group study (KGOG-3021). Cancer Res Treat.
2018;50(1):195–203.
Lee HW, Kang SY, Kim IH, Sun D-S, An HJ, Jang JS, Lee S-C, Jin M. Phase 2 study of weekly
polymeric micelle-formulated paclitaxel plus gemcitabine in patients with recurrent and metastatic adenocarcinoma of the pancreas. J Clin Oncol. 2023;41(16_suppl):e16257.
Lerchbammer-Kreith Y, Hejl M, Sommerfeld NS, Weng-Jiang X, Odunze U, Mellor RD, Workman
DG, Jakupec MA, Schatzlein AG, Uchegbu IF, Galanski MS, Keppler BK. Quaternary Ammonium Palmitoyl Glycol Chitosan (GCPQ) loaded with platinum-based anticancer agents-a novel
polymer formulation for anticancer therapy. Pharmaceuticals (Basel). 2023a;16(7):1027.
Lerchbammer-Kreith Y, Sommerfeld NS, Cseh K, Weng-Jiang X, Odunze U, Schatzlein AG,
Uchegbu IF, Galanski MS, Jakupec MA, Keppler BK. Platinum(IV)-loaded degraded glycol
chitosan as efficient platinum(IV) drug delivery platform. Pharmaceutics. 2023b;15(4):1050.
Li G, He S, Schatzlein AG, Weiss RM, Martin DT, Uchegbu IF. Achieving highly efficient gene
transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles. J
Control Release. 2021;332:210–24.
Lv PP, Wei W, Yue H, Yang TY, Wang LY, Ma GH. Porous quaternized chitosan nanoparticles
containing paclitaxel nanocrystals improved therapeutic efficacy in non-small-cell lung cancer
after oral administration. Biomacromolecules. 2011;12(12):4230–9.
Maeda H. The tumor blood vessel as an ideal target for macromolecular anticancer agents. J Control
Release. 1992;19(1–3):315– 24.
Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumour vascular permeability and the EPR effect
in macromolecular therapeutics: a review. J Control Release. 2000;65:271–84.
Mazza M, Notman R, Anwar J, Rodger A, Hicks M, Parkinson G, McCarthy D, Daviter T, Moger J,
Garrett N, Mead T, Briggs M, Schatzlein AG, Uchegbu IF. Nanofiber-based delivery of
therapeutic peptides to the brain. ACS Nano. 2013;7(2):1016–26.
Min KH, Park K, Kim YS, Bae SM, Lee S, Jo HG, Park RW, Kim IS, Jeong SY, Kim K, Kwon
IC. Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin
enhance the drug stability and tumor targeting in cancer therapy. J Control Release. 2008;127
(3):208–18.
Moger J, Garrett NL, Begley D, Mihoreanu L, Lalatsa A, Lozano M, Mazza M, Schatzlein A,
Uchegbu IF. Imaging cortical vasculature with stimulated Raman scattering and two photon
photothermal lensing microscopy. J Raman Spectrosc. 2012;43:668–74.
Na JH, Lee SY, Lee S, Koo H, Min KH, Jeong SY, Yuk SH, Kim K, Kwon IC. Effect of the stability
and deformability of self-assembled glycol chitosan nanoparticles on tumor-targeting efficiency.
J Control Release. 2012;163(1):2–9.
Nakagawa S. efficacy and safety of poly (gamma-glutamic acid) based nanoparticles (gamma-PGA
NPs) as vaccine carrier. Yakugaku Zasshi. 2008;128(11):1559–65.
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