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72 C. Unsworth et al.
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medicine development, and potentially avoid large-scale toxicology studies that
would be associated with the use of new chemical entities, including new stabilisers.
When a medicine is approved, the excipients within the formulation are no longer
considered novel, which may lead to a quicker pathway to regulatory approval. That
said, the CDER IID does also list the administration route and the concentration
within each dose of each approved medicine, and considerab
may still exist when
administration routes (e.g. an excipient used in an approved oral dose product is
required within an intravenous candidate therapy), or at concentrations within a
single administration route that have not been seen in previous approved medicines
(e.g. the use of a surfactant or polymer in a subcutaneous injection at >1.5 times the
level in previously approved clinical produ
the qualifi
study before first-in-human studies can commence.
cati
on
known pharmaceutical excipients are to be used in new
cts). I
n such cases, regulators may request
of an existing excipient/stabiliser through a detailed toxicology
le regulatory concern
4.3.3 Choice of Solvents if Required
Solvent removal is generally not entirely efficient and The International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(ICH) guidelines for residual solvents categorises pharmaceutically acceptable solvents based on their toxic potential (EMA
levels (at ppm levels) that are considered acceptable. Class one solvents are known
or suspected to be human carcinogens and should avoided, for example, benzene and
carbon tetrachloride. Class two solvents are regarded more ‘acceptable’ for medicine
development, but their use should be limited as far as reasonably feasible. Class three
solvents have a lower risk to human health and are included within this
categorisation, as they are not known to pose any hazard to humans at levels up to
5000 ppm or 50 mg/day. The lists are subject to change as new toxicological data is
generated and reviewed and solvents may change class, or have their limits revised.
Regular review of up-to-date information is highly recommended.
2021). The guidelines also list the residual
4.3.4 Translation to Clinical Scale
One major hurdle to overcome in the development of novel medicinal products is the
translation from laboratory scale to larger-scale production. (Feng et al. 2019)
Consideration of industrial feasibility from the outset of nanomedicine design
considerably aids the acceleration of translation times from laboratory to clinic
(Malhaire and Lagarce 2015).
The use of complex, multi-step particle generation and drying steps, and the use
of cost-ineffective materials can slow or halt the translation of a particular nanoparticle material for economic reasons. At industrial scale, factors such as long process
4 Solid Drug Nanoparticles 73
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times for approaches such as milling, extended feed times for spray drying or
multiple secondary drying steps after processing can lead to high production costs
and diseconomies of scale, decreasing the likelihood of a potential therapy reaching
clinical evaluation (Bosetti and Jones
critical for parenteral products, during all steps of manufacturing can be difficult, and
production of sterile spray dried material is particularly challenging (Ohori et al.
2021)
, making terminal sterilisation a common process where in-line sterilisation
cannot
irradiation, chemical techniques, sterile filtration, and the most commonly used
technique throughout the pharmaceutical industry, thermal sterilisation processes
(Armenante and Akiti
and material properties must be ensured. This is all the more challenging when
adding the demands of Good Manuf acturing Practice (GMP) quality guidelines
(Ðorđević et al.
particle synthesis, as well as volume and turbulence-linked alterations (heat and
mass-transfer) within reaction vessels and drying equipment when translating
laboratory-scale technologies to pilot plant and large-scale scale processes must be
addressed (Tchessalov et al. 2022). Numerical modelling as well as empirical studies
are often used in combination to optimise parameters (Kramer et al. 2009).
be
assured (Hasanai
At each step of particle manufacturing and material production, control of particle
2022). Differences in reaction kinetics and fluid mechanics during
n et al.
2019).
2019). The maintenance of sterile conditions,
2014). Sterilisation may be achieved through
4.4 Applications of Solid Drug Nanoparticles
The novel properties of SDNs have facilitated the development of a number of
advancements in the dosing of poorly water-soluble APIs. Nanoparticle formulations
have been found to improve the dissolution of APIs, thus improving the bioavailability compared with unformulated drug compounds. Clinical therapeutics utilising
SDNs are benefiting patients globally, across a number of different administration
routes and varying indications.
4.4.1 SDNs in Orally Dosed Medicines
Oral delivery of SDNs has been researched heavily for some years, with the majority
of FDA-approved nanomedicines containing SDN-derived formulations for oral
administration (Table 4.1) (Vasconcelos et al. 2016; Jermain et al. 2018; Verma
et al. 2021; Malamatari et al. 2018; de Waard et al. 2011; Merisko-Liversidge and
Liversidge 2008; Pandi et al. 2020). Oral dosing is often the most simple route of
administration for many drugs, due to low treatment costs, high patient-preference,
non-invasive nature of administration and minimal sterility requirements compared
with parenteral medicines (Khan et al. 2022; Wang et al. 2020). Drugs with poor
water solubility often require high doses to attempt to reach systemic concentrations
74 C. Unsworth et al.
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2018), and de Waard et al. (2011)
(
FDA
approval References
1999 Merisko-Liversidge and Liversidge (2008)
Processing
Active
Table 4.1 Solid drug nanoparticles in commercially available clinical products
technology Company
Cystic fibrosis Spray drying Vertex 2016 Vasconcelos et al. (2016)
Lumacaftor/
ingredient(s) Indication
®
Product
Oral administration
Orkambi
Ivacaftor
Ivacaftor Cystic fibrosis Spray drying Vertex 2012 Vasconcelos et al. (2016)
®
®
Kalydeco
Hepatitis C Spray drying Gilead Sciences 2016 Jermain et al. (2018)
Suvorexant Insomnia Melt extrusion Merck 2014 Jermain et al. (2018)
Sofobuvir/
Velpatasvir
®
Epclusa
Belsomra
Hepatitis C Melt extrusion AbbVie 2017 Jermain et al. (2018)
Teleprevir Hepatitis C Spray drying Vertex 2011 Vasconcelos et al. (2016)
Glecapravir/
®
®
Mavyret
Incivek
Hepatitis C Spray drying Merck 2016 Jermain et al. (2018)
pibrentasvir
Elbasvir/
grazoprevir
®
®
Zepatier
Roche 2011 Vasconcelos et al. (2016)
precipitation
Hepatitis C Spray drying Gilead Sciences 2014 Jermain et al. (2018)
Ledipasvir/
sofosbuvir
Vemurafenib Melanoma Solvent/antisolvent
®
Harvoni
Zelboraf
Griseofulvin Antifungal Coprecipitation Novartis 1982 Verma et al. (2021), Malamatari et al.
®
Gris-PEG
Wyeth-Ayerst
Research
®
NanoCrystal
HIV Melt extrusion AbbVie 2007 Jermain et al. (2018)
Posaconazole Antifungal Melt extrusion Merck 2013 Vasconcelos et al. (2016)
Itraconazole Antifungal Melt extrusion Merz Pharma 2010 Vasconcelos et al. (2016)
Venetoclax Leukaemia Melt extrusion AbbVie 2016 Jermain et al. (2018)
Sirolimus Immunosuppressant Milling/
Everolimus Immunosuppressant Spray drying Novartis 2010 Vasconcelos et al. (2016)
Tacrolimus Immunosuppressant Wet granulation Astallas Pharma 2013 Pandi et al. (2020)
Lopinavir/
Ritonavir
®
®
®
®
Onmel
Venclexta
Rapamune
Noxafil
®
®
Zortress
Astagraf XL
®
Kaletra
4 Solid Drug Nanoparticles 75
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2005 Merisko-Liversidge and Liversidge (2008)
2004 Merisko-Liversidge and Liversidge (2008)
Par Pharmaceuti-
cal Inc.
Abbott
Laboratories
®
®
NanoCrystal
NanoCrystal
Appetite stimulant Milling/
et al. (2011)
Merck 2003 Merisko-Liversidge and Liversidge (2008)
Novartis 2013 Chaurasiya and Zhao (2020) and Geller
®
NanoCrystal
et al. (2011)
sion spray drying
Insmed Limited 2018 Yue et al. (2022)
Liposome
suspension
avium complex
(2018)
Janssen 2009 Verma et al. (2021) and Malamatari et al.
Janssen 2015 Verma et al. (2021)
®
NanoCrystal
Antipsychotic Milling/
Antipsychotic Milling/
2014 Verma et al. (2021)
Eagle
Pharmaceuticals
®
NanoCrystal
Freeze dried
nanosuspension
hyperthermia
Wet media milling Alcon 1998 Malamatari et al. (2018)
HIV Milling ViiV Healthcare 2020 Surve and Jindal (2020)
hypertension
Ritonavir HIV Melt extrusion AbbVie 2010 Pandi et al. (2020)
Megestrol
acetate
Fenofibrate Antilipemic agent Milling/
®
Megace ES
Norvir
®
TriCor
®
Nabilone Antiemetic Precipitation Valeant 1985 Malamatari et al. (2018) and de Waard
®
Cesamet
Aprepitant Antiemetic Milling/
®
Emend
Tobramycin Cystic fibrosis Oil in water emul-
TOBI
Podhaler® Capsules
®
®
Inhalable administration
Zanamivir Influenza Spray drying GlaxoSmithKline 2000 Chaurasiya and Zhao (2020)
Amikacin Mycobacterium
®
Arikayce
Relenza
Paliperidone
Palmitate
Paliperidone
®
®
®
®
Sustenna
Invega
Invega
Injectable administration
Palmitate
Dantrolene Malignant
®
Trinza
Ryanodex
Rilpivirine/
cabotegravir
®
Ocular administration
Cabenuva
Brinzolamide Ocular
®
Azopt
76 C. Unsworth et al.
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within the therapeutic window, due to poor absorption and elimination through the
gastrointestinal tract prior to their dissolution (Khan et al. 2022). Furthermore, the
harsh biochemical environment within the gastrointestinal tract can affect the stability of some drugs, leading to further complications with oral drug delivery (Wang
et al.
2020). With the advancements in processing of SDNS and the enhancement of
dissolution kinetics that may be achieved, improved bioavailability that is often seen
from SDNs offers an attractive proposition for drug manufacturers to reformulate
poorly water-soluble or pH-sensitive drugs, rather than seek new alternatives
(Bhalani et al.
2022).
As mentioned previously, one particular technology that has been used extensively in the development of nanomedicine drug products is nanomilling. Initially
developed at scale by Elan Drug Technologies, and sometimes referred to as
NanoCrystal
®
technology, this high-energy media milling approach for poorly
water-soluble drugs has arguably been the most successful nanomedicine platform
for generating FDA-approved drug products. Milling often uses highly cross-linked
polystyrene beads to avoid attrition within the mill, and generally regarded as safe
(GRAS) excipients or excipients chosen from the CDER IID (Merisko-Liversidge
and Liversidge 2011). The resulting process usually produces a crystalline dispersion, due to the attrition of larger crystalline structures, with a particle size of
approximately 1 micron or less (Merisko-Liversidge and Liversidge 2008).
Poor drug bioavailability as a result of chemical instability or pH-dependent
solubility can also be influenced by excipient choice and encapsulation technologies
(Huh et al.
Eudragit
2012; Drummond et al. 2000). Polymers such as the (meth)acrylic
®
copolymer range have gained a great deal of attention for their pH
sensitivity, since they were first developed as film coating agents (Yadav et al.
2012; Patra et al. 2017). Eudragit RPLO, a copolymer of ethyl acrylate and methyl
methacrylate, in particular, has been studied for its sustained release properties and
has been incorporated into drug nanoparticle formulations for oral delivery. (Ya dav
2012; Patra et al.
et al.
2017; Gandhi et al. 2014; Hajba-Horváth et al. 2021) Yadav
et al. reported a nearly twofold increase in the bioavailability of the diabetes
medication glimepiride, a drug which shows pH-dependent solubility, when formulating it into nanoparticles with Eudragit RPLO (Yadav et al. 2012). Similarly,
Hajba-Hováth et al. used in silico modelling to predict a dose reduction of
60–70% using valsartan/Eudragit RLPO nanoparticles compared with a capsule
formulation of valsartan (Hajba-Horváth et al.
2021). Although not technically
SDNs, solid lipid nanoparticles (SLN) are another strategy adopted by researchers
for the delivery of pH-sensitive drug compounds (Borges et al.
2020; Chokshi et al.
2018; Yang et al. 2022; Li et al. 2019). Whilst the concept of SLN has been around
since the early 1990s (Lucks and Müller
1991), the recent use of SLNs within the
Pfizer-BioNTech COVID-19 mRNA vaccine has sparked renewed interest into this
drug encapsulation method (Anselmo and Mitragotri
2021). Prior to the use of SLNs
in the clinic, SLNs were predominantly focussed on the delivery of cancer chemotherapeutics, as studies indicated that they exhibit advantages over free drug, such as
enhanced solubility and improved pharmacokinetics, efficacy and minimal toxicity.
(Thi et al.
2021) In the case of doxorubicin, pegylated liposomal formulations have
4 Solid Drug Nanoparticles 77
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been reported to inhibit the uptake of doxorubicin into placental tissue, and showed
lower cellular uptake and toxicity compared to unformulated doxorubicin,
suggesting it is possible to mitigate some of the unwanted side effects associated
with administration of this drug (Soininen et al.
2015).
4.4.2 Parenteral Administration of SDNs
Parenteral administration is an alternative approach for drug delivery, as it can
mitigate some of the limitations of oral drug delivery, mainly drug absorption,
the physiological barriers within the gastrointest inal tract and fi rst-pass metabolism
(Alqahtani et al. 2021; Kenyon and Hughes 2010). Parenteral administration is
defined as drug dosing that occurs outside of the intestine (enteral dosing), but is
often used to refer to drug delivery by injection. Injections can be intravenous,
intramuscular, subcutaneous, intradermal and the least common intraarterial (Kim
and De Jesus 2022). Whilst injectable formulations have some advantages over oral
formulations, they still suffer from the same limitations when it comes to drug
solubility. Moreover, there are formulation considerations needed to ensure the
safety and efficacy of injectable nanoparticle dispersions. These include the
following:
. Sterility: The presence of any microbial contaminants in an injectable drug
product could be detrimental to patient health. Therefore, all injectable drug
products must undergo sterilisation to ensure patient safety. Sterility of injectable
products can be achieved by aseptic processing or through terminal sterilisation
using dry heat treatment or gamma irradiation for dry powders (Patel et al.
The choice of sterilisation technique to apply to SDNs is often driven by the
formulation itself, as some terminal sterilisation processes can negatively impact
the particle size or dispersion characteristics of the formulation (Shegokar and
Singh 2012). In some circumstances, components of the formulation such as the
API or excipients can be chemi cally altered by gamma irradiation (Hasanain et al.
2014). Alternatives such as aseptic processing of sterile API and excipients, or
sterile filtration of nanosuspensions, may be appropriate for products that are not
able to withstand terminal sterilisation (Zheng and Bosch 1997; Gonella et al.
2022).
.
Osmolality: Osmolality is the measure of dissolved species, and is reported as the
number of solute particles per kilogram of solvent (Koeppen and Stanton
The osmolality of blood typically falls between 285 and 310 mOsmol/kg, making
the ideal osmolality of an injectable drug product around 300 mOsmol/kg
(Taghizadeh et al. 2022). Injection of solutions/suspensions with higher osmolality (hypertonic) or lower osmolality (hypotonic) than blood can cause pain to
the patient. For subcutaneous administration, a hypertonic solution can be tolerated to reduce injection volume, with 600 mOsmol/kg suggested as the upper
limit to minimise hypertonicity-induced pain (Usach et al.
2019).
2020).
2013).
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. pH: Medicinal products are typically formulated to match physiological pH to
minimise tissue damage, irritation and pain. Exceptions to this are in the case of
APIs that have pH-dependent solubility or stability issues. Ideally, the pH of a
solution or suspension for injectable administration is between 3.5 and 9, as it has
been reported that a pH greater than 9 can lead to tissue necrosis, and pH lower
than 3 can cause pain and phlebitis (Broadhead and Gibson
2009). For SDN
suspensions, the pH can be adjusted during the formulation development; however, in instances where the API exhibi ts pH-dependent solubility, altering the pH
may lead to Ostwald ripening of the particles and potential increases in particle
size distributions.
. Dispersibility and reconstitution: In the case where dry powders for reconstitu-
tion at the point of administration are prepared, the powder must redisperse easily
with gentle agitation in its chosen diluent. The dispersion should be uniform, and
in the case of injectables for intramuscular or subcutaneous administration, pass
easily through small bore needles, as larger needle diameters are linked to more
painful needle insertions. Highly uniform SDN suspensions upon redispersion are
desirable for such administration routes (Usach et al.
2019).
4.4.2.1 Intravenous Injectables
Intravenous drug administration is highly desirable under certain clinical settings,
allowing immediate and prolonged release of drug into the systemic circulation. This
is particularly important in emergency medical situations, where delays can cause
irreversible internal damage or even patient mortality. Eagle Pharmaceuticals developed a lyophilised formulation, Ryanodex
®
, of a dantrolene sodium nanosuspension
that is reconstituted with sterile water before intravenous injection for the treatment
of malignant hyperthermia. Conventional treatment involves the dosing of
dantrolene sodium, which can only be administered 20 mg at a time, requiring a
large number of vials to be reconstituted, and significant time delay to administer the
appropriate dose (Rosenberg et al.
2015). Ryanodex
®
is 150 times more concentrated than dantrolene sodium, allowing for smaller injection volumes to achieve the
same dose (Schütte et al.
2011). With intravenous nanoparticulate therapies, particle
size is considered to play a part in the dissolution of the drug into the bloodstream.
For fast drug dissolution, a mean particle diameter of 100–200 nm particles are
preferred; however, for prolonged dissolution, particles in the upper nanometre
range of 800–1000 nm are desired (Müller et al.
2001). Prolonged dissolution is
advantageous for the treatment of infections that target the mononuclear phagocytic
system, such as tuberculosis, listeriosis, leishmaniasis and toxoplasmosis, to allow
for the particles to be taken up by macrophages before dissolution occurs (Patel et al.
2020).
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4.4.2.2 Subcutaneous and Intramuscular Injectables
The development of long-acting injectables designed for subcutaneous and intramuscular injection has gained much inte rest, with the benefits of long-acting therapies being utilised in the treatment of chronic diseases, such as HIV and
schizophrenia. Long-acting therapies can provide a slow, sustained drug release
into the body over a period of weeks or, in some cases, months (Owen and Rannard
2016b). Two formulations of the antipsychotic drug paliperidone palmitate, prepared
using the NanoCrystal
Both formulations contain the same API but have different dosing regimens, with
Invega Sustenna
®
technology approach, have been developed by Janssen.
®
given as a monthly intramuscular injection and Invega Trinza
administered every 3 months (Ravenstijn et al. 2016). The difference in release
profile of these two long acting injectable products is attributed to the difference in
particle size between the two formulations (Daghistani and Rey 2016). A similar
drug release phenomenon was observed in vitro with a nanosuspension of riboflavin
laurate, which were prepared using a bottom-up/top-down approach involving highpressure homogenisation (Hu et al.
2014a; Hu et al. 2014b).
Long-acting injectable SDN formulations can overcome the challenges of patient
adherence observed with oral medications. For example, HIV medications often
require daily oral dosing, with the result of missed doses leading to poor control of
viral replication and possible drug resistance (Smith
2006). Cabenuva
®
was developed using wet media milling for the treatment of HIV, and consists of two separate
intramuscular injections individually containing the antiretroviral drugs cabotegravir
or rilpivirine. The treatment is administered once a month. Similarly, patient adherence can impact the effectiveness of oral prophylaxis regimes for the prevention of
infectious diseases. Bakshi et al. have reported an ETFD approach for the preparation of SDNs of the antimalarial drug atovaquone, at a drug loading of 80 wt%
relative to excipients. (Bakshi et al. 2018 ) The resulting dispersion was able to
provide complete protection against malarial sporozoite challenges for up to 4 weeks
after a single intramuscular injection in mice. The same methodology has been
applied to the antiretroviral drugs maraviroc and prodrugs of emtricitabine for
injectable administration (Tatham et al.
2019; Hobson et al. 2019b), as well as a
number of different APIs for oral administration, all of which report improved
bioavailability compared with API alone (Giardiello et al. 2016; McDonald et al.
2014; Savage et al. 2019; Elbaz et al. 2021).
®
4.4.2.3 Inhalable Administration
Inhalable drug nanoparticles also offer an opportunity for targeted drug delivery of
poorly water-soluble drugs to the lungs and respiratory tract and inhalable administration is a popular option for treating respiratory infections or diseases. Drug
delivery to the lungs is typically administered by pressurised metered dose inhalers,
dry powder inhalers or nebulisers (Newman
2017). Particle size can strongly
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influence the region of lungs where deposition occurs, with relatively large particles
>5 μm) being deposited in the mouth and upper airway and smaller particles
(d
a
¼ 1–5 μm), depositing deeper into the small airways of the lungs (Sung et al.
(d
a
2007). Nanoparticles deposit with high efficiency in the entire respiratory tract due to
diffusion, making them a good candidate for pulmonary drug delivery (Geiser and
Kreyling 2010). A study to compare the fate of salbutamol nanoparticles in the lungs
with micronised salbutamol has been reported using the radiolabel tracer
99m
Tc
(Bhavna et al. 2009). Whole lung deposition of salbutamol nanoparticles was
reported as
approximately 64.1%, compared with 28.3% for the micronised
salbutamol. The majority of the micronised salbutamol deposited in the mouth,
pharynx, oesophagus and oropharynx-stomach, similar to observations made with
99m
Tc labelled budesonide and terbutaline micronised powders (Borgstrom et al.
1994).
Interestingly, whilst the use of nanoparticles delivered by inhalation has shown
enhanced dissolution and an increase in bioavailability of several APIs (Pramanik
et al.
2021), in some cases researchers have also reported a sustained release of API
compared with dosing of pure API (Debnath et al. 2018; Garg et al. 2016) or in some
cases other administration routes (Zhang et al. 2001; Kawashima et al. 1999; Pandey
et al. 2003; Rawal et al. 2017; Zahoor et al. 2005). The formulation of drugs into
nanoparticles provides the opportunity to administer poorly water-soluble drugs to
the lungs that would not normally be possible without modification. Yu et al.
prepared ivacaftor nanosuspensions and incorporated them into microparticles in
the presence of a second API colistin for the inhalable treatment of the lung infection
caused by Psuedomonas aeruginosa (Yu et al.
2021). The nanosuspensions were
prepared using a solvent/antisolvent method in the presence of stabilisers and
colistin, and spray-freeze dried to produce microparticles for inhalable drug delivery.
In vitro studies of the formulation compared to a jet-milled physical mixture of the
two drugs showed improved drug release of ivacaftor and good aerosol behaviour
relative to the physical mixture which could not be aerosolised.
4.4.2.4 Topical Administration
Topical drug delivery is the delivery of a drug to localised areas of the skin, with
minimal systemic absorption. In contrast, transdermal drug delivery refers to the
delivery of drug systemically by applying the formulation directly to healthy intact
skin. It is a painless, non-invasive method of drug delivery whereby the drug
penetrates through the layers of skin into the dermal layer, and becomes available
for systemic absorption via the dermal microcirculation (Alkilani et al.
methods of drug delivery through the skin have seen benefits from the use of drug
nanoparticles for the delivery of poorly water-soluble drugs. Nanoparticles administered to the skin are believed to be able to pass through the lipid layer of the stratum
corneum or get entrapped within hair follicles, and subsequent dissolution may
facilitate the diffusion deeper into the skin layers (Parmar et al.
2015). Both
2021).
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Topical administration for drug delivery focuses on the treatment of skin disorders, such as infections, inflammation and psoriasis. Whilst drug delivery is localised
to within the skin after administration of topical formulations, permeation of APIs is
still hindered by the excellent barrier properties of the skin, but can be improved with
SDNs due to the increase in surface area of the particles which increases surface
contact and enables rapid dissolution (Parmar et al.
dermal routes is desirable as it provides a non-i nvasive alternative to injectable
delivery, with a more uniform pharmacokinetic profile which can reduce side effects.
As with injectable administration, transdermal drug delivery also avoids first-pass
metabolism of the API, promoting concentrations within systemic circulation (Han
and Das
of different administration methods, for treatments such as non-steroidal anti-inflammatory drugs and hormone replacement therapy (Kumar et al. 2018; Valenzuela and
Simon 2012 ). Piao et al. reported the use of solid-in-oil nanosuspensions for the
delivery of an NSAID. When administered directly onto the skin, the solid-in-oil
nanosuspensions exhibited a 3.8-fold increase in skin permeation compared with
unformulated drug (Piao et al.
patches, drug nanoparticles have shown bett er skin permeation than the drug
nanosuspension alone. For example, by embedding a nanosuspension of the poorly
water-soluble drug cholecalciferol into a dissolving microneedle array, significantly
higher skin permeation was observed with the nanosuspension in dissolving
microneedle arrays compa red with a patch made of the nanosuspension alone
(Vora et al. 2018). Alternatively, delivery of SDNs via solid microneedle patches
has been demonstrated (Morris et al. 2023).
2015). SDNs have been used for transdermal drug delivery to aid a variety
2008). With incorporation into microneedle array
2021). Drug delivery by trans-
4.4.2.5 Ocular Delivery
Treatment of conditions affecting the eye often consists of administration of a drug
in the form of eye drops. Nanoparticle-based ophthalmic formulations have been
found to have a number of advantages (Omerović and Vranić
following:
1. Increased permeability and bioavailability of drug
2. Extended retention on the surface of the eye
3. Improved interaction with the cornea
4. Reduced degradation of unstable drug
Furthermore, particles of smaller size have been noted to cause less irritation and
inflammation upon administration, making treatment less uncomfortable for the
patient. The majority of the current research into drug nanoparticles for ocular
drug delivery includes the use of solid lipid nanoparticles or polymeric
nanoparticles. Both nanoparticle-based systems have been found to exhibit sustained
release of drug to the eye, attributed to size and mucoadhesive properties of the
nanoparticles (Alme ida et al.
of topical ophthalmic treatments, and polycaprolactone nanoparticles have also been
2020), including the
). Drug delivery to the eye is not limited to the use
2014
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