‫جامعة العلوم والتكنولوجيا االردنية‬

‫كلية الدراسات العليا‬

‫مقترح مشروع بحث رسالة الماجستير‬

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‫البرنامج‬ ‫البريد اإللكتروني‬ ‫الرقم الجامعي‬ ‫اسم الطالب‬

‫الماجستير‬ Saabualsameed21@nano.just.edu.jo 150651 ‫سناء امين عليان ابو السميد‬
‫التاريخ‬ ‫الكليـة‬ ‫القسم‬ ‫التخصص‬
‫معهد النانوتكنولوجي‬ ‫هندسه وعلوم‬ ‫هندسة وعلوم‬
‫النانوتكنولوجي‬ ‫النانوتكنولوجي‬
‫توقيع المشرف الرئيس‬ ‫البريد االلكتروني للمشرف الرئيس‬ ‫اسم المشرف الرئيس‬

‫البريد االلكتروني للمشرف المشارك‬ ‫اسم المشرف المشارك‬

‫عنوان مقترح البحث باللغة العربية‬

I. Title of the Proposed Project (No abbreviations in the title)

The title in English should conform to the title in Arabic.
Suggested titles.
1. fabrication of nanoneedle eyelid patch for effective ocular drug delivery.
2. Nanoneedle-assisted transdermal delivery of nano hyaluronic acid for dry eye disease.
3. A Novel Ocular drug delivery system: Nanoneedle eyelid patch.

II. Introduction and Hypothesis of the Study (minimum of 300 words):

Numerous approaches to drug delivery systems have been studied to deliver drugs to the proper organ. In recent
years, the field of ocular drug delivery has become a hotspot for researchers and scientists to investigate and
improve methods of delivering drugs to the eye [1]. Because it is an isolated organ with a complex anatomical
structure, it is also challenging to administer medications correctly [2]. Ocular disease has a significant impact
on the quality of life; according to the World Health Organization’s (WHO) report from 2022, at least 2.2 billion
people globally have near-or distance-vision impairment, and almost half of these cases could have been pre-
vented [3]

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 Reduced vision can be brought on by several conditions, including eye trauma, age-related macular degeneration
(AMD), glaucoma, cataracts, dry eye, and infectious diseases that require frequent drug administration[4]. Dry
eye disease is a multifactorial disease characterized by tear film instability and ocular surface inflammation that
results in symptoms of discomfort, fatigue, visual disturbances and blurred vision[5].
Dry eye disease is one of the most prevalent diseases nowadays [6]. Due to the widespread overuse of digital
devices in general and new technology like smartphones and computers, it affects more than 35% of the world's
population. Additionally, some people experience dry eyes as they age. That can be due to age-related decreases
in tear production or blood flow to the eye's surface (vascular endothelial dysfunction) [7 , 8].

Multiple routes, including systematic, oral, topical, intravitreal, and subretinal, can be used to administer medi-
cations for treating ocular diseases [9]. Topical drug administration, primarily the use of eye drops, is the most
popular method of delivering medications to the eyes because it is non-invasive, simple to use, compatible, and
has a high patient compliance rate [10]. However, it has several drawbacks, including low bioavailability, poor
targeting, a high dose, or repeated topical applications. This burdens patients and raises the risk of side effects
like keratitis, blurred vision, and eye discomfort. Most importantly, administering while asleep is impossible.

The unique physiology, anatomy, and biochemistry of the eye have made effective ocular drug delivery an on-
going challenge. As a result, it has developed resistance to some active molecules. Therefore, technologists
should create effective drug delivery systems with high targeting capability and minimal tissue damage to over-
come ocular barriers [11]. The primary anatomical and physiological barriers that obstruct bioavailability in-
clude tear dilution and turnover, nasolacrimal drainage, reflex blinking, and the static and dynamic barriers of
the eye, which have limited absorption to below 5% in conventional formulations [12].

This drew researchers' attention to the delivery of ocular drugs through the lower eyelid skin. In contrast with
the upper eyelid, the lower eyelid is almost immobile, has a thin stratum corneum, and can penetrate drugs into
the conjunctiva, making it an ideal delivery system for ocular drugs.[13]. Eyelid skin is also rich in sebaceous
glands that have a high density of capillaries and lymphatic vessels [14]. This makes it more permeable to
drugs than other parts of the body. The administration of drugs through the skin also has several advantages,
such as avoiding premature metabolism, decreasing toxicity, minimizing side effects, and enhancing patient
compliance [15].

Eyelids have a unique feature from the standpoint of drug delivery. They are close to the conjunctiva and di-
rectly interact with the ocular tissue surrounding the eyeball. Approximately 30 times more permeable than the
cornea [16]. This enables drug treatments to target anterior and posterior ocular compartments for most ocular
diseases[17].

Additionally, transdermal drug delivery may maintain a constant concentration of drug in the dermal layers
underneath the application site for an extended period [18]. This is the most advantageous feature compared to
eye drops, which have significant drawbacks. These problems associated with eye drops could be overcome if
medications could be administered to the conjunctival tissue via the eyelid skin. Moreover, once drugs are pre-
pared for eyelid delivery, patients with ocular disorders (e.g., eye dryness, allergic conjunctivitis, eye infections,
glaucoma) and healthcare providers benefit from increased convenience[19]. Drug administration time by pa-
tients or health care providers is minimized. At the same time, therapy can continue even while the patient is
asleep by boosting drug retention duration and, as a result, patient comfort and quality of life [20,21].

This experiment aims to fabricate and evaluate eye patches that deliver drugs to the eye using nanotechnology
owing to the need for more data about eyelid drug permeation and the limited number of studies investigating
drug delivery into the conjunctiva through the eyelid skin [22].

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 Nanotechnology refers to the science that deals with materials with at least one dimension at the nanoscale (1–
100 nm) [23]. Those materials are among the most impressive and applicable fundamentals in today’s advanced
research, owing to their tiny size; in addition to their significantly large surface-to-volume ratio, nanomaterials
have enhanced physical and chemical features compared to their bulk structure [24].

Nanoneedles have high aspect ratio structures with diameters less than 100 nm, while their height range is be-
tween 1 and 20 nm. This increases their pore volume compared to other solid structures like microneedles,
improves payload density by several orders of magnitude and creates a significant reservoir for the loading of
drugs [25]. Nanoneedles can penetrate cell membranes and deliver cargo into internal cells with little to no skin
irritation or disruption of the cells. After delivery, they can maintain cells in a generally stable, healthy state
[26].

This study aims to fill the gap and formulate nanoneedle eyelid patches that deliver drugs to the ocular tissue
practically, even though no studies have used nanoneedles to deliver drugs throughout the eyelid.

This project hypothesizes that “A novel formulation of nanoneedle eyelid patches for ocular drug delivery
as transdermal drug delivery that will be highly effective, minimally invasive, and have high bioavailabil-
ity”.

III. Aims of the study:

This project aims to formulate and evaluate a nanoneedle eyelid patch as transdermal drug delivery to overcome
the drawbacks of conventional ocular drug delivery.
This can be done by:
1. Fabrication of nanoneedles patch.
2. Characterization of nanoneedles.
3. Evaluation of drug loading and release.

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 IV. Materials and Methods:

Materials

Polydimethylsiloxane (PDMS), nanoneedle stainless steel mold, methyl hyaluronic acid, and nanosized
hyaluronic acid.

Method

1. Fabrication of nanoneedle eyepatch.

Nanoneedles patches will be fabricated using a simple nano molding method.

1. PDMS nano molds will be prepared by pouring PDMS solution into the custom-designed stainless
steel master mold.
2. Then will be degassed, cured and applied to the plasma to remove any air bubbles.
3. Methyl hyaluronic acid aqueous solution will be cast into the plasma-treated PDMS through cen-
trifugation.
4. Then will be air-dried at room temperature in a fume hood overnight.
5. Unmodified -Hyaluronic acid solution will be applied and centrifuged to fill the Nanoneedle cavi-
ties.
6. HA solution will be added to produce a robust supporting substrate and dried overnight.
7. As shown in the figure below, Nanoneedle patches will be gently peeled off from the nano molds
and exposed to low-intensity ultraviolet.

Schematic illustration. Fabrication of polymeric nanoneedle patch[27].

2. Characterization of Nanoneedles patch

Upon availability, several characterization methods will be used:

1. Scanning electron microscopy (SEM) to determine the surface morphology and size of the
nanoneedles. (HR-SEM, TEM, )
2. UV-vis spectrometer to show the optical absorption edge of the synthesized nanoneedles.
3. Atomic force microscope (AFM) to show the topography of the nanoneedle structure.

3. Evaluation of Drug release of Nanoneedles

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 i. In vitro tolerance studies using Franz cell lines. To be determined by the advisor
ii. In Vivo tolerance studies using animal study. To be determined by the advisor

V. References

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[2] N. Üstündaǧ Okur, E. Ş. Çaǧlar, and P. I. Siafaka, “Novel Ocular Drug Delivery Systems: An Update
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10.1089/JOP.2019.0135.
[3] D. Sakpal, S. Gharat, and M. Momin, “Biomaterials Advances Recent advancements in polymeric nan-
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