







































Education, Society and Human Studies 
ISSN 2690-3679 (Print) ISSN 2690-3687 (Online) 

Vol. 3, No. 1, 2022 
www.scholink.org/ojs/index.php/eshs 

9 

Original Paper 

Ultra Flexible Nanocarrier for Enhanced the Ocular Delivery of 

Quercetin in Management of Macular Edema 
Sahu Seema1, Shah Gulab Chand2, Manigauha Ashish1, & Gupta Vandana1 

1 MITTAL INSTITUTE OF PHARMACY Opposite to Bhopal Memorial Hospital and Research Center 

(BMHRC) Nbibagh, Karond, Bhopal-462038 (M.P) 
2 School of Biotechnology RGPV BHOPAL, 462033 (M.P) 
* Sahu Seema, MITTAL INSTITUTE OF PHARMACY Opposite to Bhopal Memorial Hospital and 

Research Center (BMHRC) Nbibagh, Karond, Bhopal-462038 (M.P) 

 

Received: December 22, 2020    Accepted: January 14, 2021   Online Published: December 14, 2021 

doi:10.22158/eshs.v3n1p9                         URL: http://dx.doi.org/10.22158/eshs.v3n1p9 

 

Abstract 

Quercetin (Que) and its derivatives are naturally taking place phytochemicals with promising bioactive 

belongings. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer’s, 

antiarthritic, cardiovascular, and wound-healing possessions of Que have been extensively investigated, 

as well as its anticancer commotion against different cancer cell lines has been newly reported. Que 

and its derivatives are found predominantly in the Western starve yourself, and people might benefit 

from their defensive effect just by taking them via diets or as a food enhancement. 

Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que 

nanoparticles become visible as a promising proposal to enhance their bioavailability. The present 

review aims to make available a brief overview of the therapeutic things, new insights, and forthcoming 

perspectives of Que. Plants and plant parts are used for its aroma, flavor, or therapeutic properties. 

There are a number of recompense associated with using plants and plant phytoconstituents as 

contrasting to pharmaceutical merchandise. 

Keywords 

Quercetin (Que), Ultraviolet(UV), Thermogravimetric Analysis (TGA), Solid lipid Nanoparticle (SLN), 

Polyethylene Oxide (PEO), Isotonic Phosphate Buffer Saline (IPBS) 

 

 

 

 



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1. Introduction 

With increased age comes declining health conditions and increased prevalence in diseases. Included in 

this broad category is the deterioration of vision due to a variety of factors contributing to a number of 

ophthalmic diseases. These diseases can include age-related macular degeneration, cataracts, diabetic 

retinopathy, and glaucoma. According to statistics by the National Eye Institute, several millions of 

people above the age of forty are affected by one of these conditions. From the total population of those 

above age forty in the 2010 U.S. Census (n = 142,648,393), 36,883,997 adults suffered from vision 

impairment due to all of the ophthalmic diseases listed above combined (NEI “Prevalence”, 2016). This 

is approximately over a quarter (25.9%) of adults over age forty who are affected with vision 

impairment. As age increases, the prevalence rates of all vision impairment also increase, rising 

significantly around ages 75-79 in all ethnicities, as shown in Figure 1. 

 

 
Figure 1. 2010 U.S. Prevalence Rates: All Vision Impairment 

Source: National Eye Institute. All Vision Impairment. Available at: 

https://nei.nih.gov/eyedata/vision_impaired#1. Accessed March 27, 2020 

 

Over the course of ten years, starting from the year 2000, the prevalence of vision impairment has 

increased by almost 130% (NEI “Vision”, 2016). These trends are expected to continue with each 

subsequent year so that by the year 2030, there will be almost a two-fold increase in prevalence of 

vision impairment compared to that in 2010, and by 2050, there will be more than a 3-fold increase in 

prevalence, as shown in Table 1 and Figure: 2. 

 

 

 



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Table 1. Table Projections for Vision Impairment (2010-2030-2050) 

Year All White Black Hispanic Other 

2010 4,195,966 3,398,977 330,644 290,781 175,564 

2030 7,169,680 5,277,689 618,110 840,497 433,383 

2050 13,026,870 9,019,189 1,0470,986 2,000,853 958,842 

Total 

Population 

142,648393 103,846,437 15,190,777 14,901,369 8,709,810 

Source: National Eye Institute. Vision Impairment Tables. Available at: https://nei.nih.gov/ 

eyedata/vision_impaired/tables. Accessed March 27, 2020 

 

Figure. 2 Chart Projections for Vision Impairment (2010-2030-2050) 

Source: National Eye Institute. All Vision Impairment. Available at: 

https://nei.nih.gov/eyedata/vision_impaired#1. Accessed March 27, 2020 

 

One cause of vision impairment is due to uncontrolled exposure to reactive oxidative species, or ROS. 

These are species that are produced naturally in the body as a byproduct of adenosine triphosphate, or 

ATP, production, the energy source that is used for every day function and processes (Prunty, 2015). 

They are free radicals that contain oxygen and are the most common type produced in tissues (NCI, 

2014). They can affect cells by damaging important cellular components, such as DNA, proteins, and 

membranes. The mitochondria, an efficient organelle found abundantly in the body’s cells and tissues, 

produce the largest quantities of ROS as it is the largest contributor to ATP synthesis (90% of the 

body’s energy) [UMDF, 2017]. The body has natural antioxidant mechanisms to protect against ROS, 

but when ROS are overproduced, these mechanisms are overwhelmed (Prunty, 2015). This leads to 



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oxidative stress cascades on cells and tissues, which causes them to become damaged and eventually 

die off. In the eye, ROS damage the cells of the retina, which plays an important role in converting 

visual images into electrical impulses for the brain to interpret. As the photoreceptor cells of the retina 

die off, vision worsens as the eye has less capability to convert those images to impulses. The longer 

the period of exposure to ROS, the more damage is done to the retina. Prolonged damage to the retina 

exacerbates retinal degradation and degeneration, further impairing vision and may even lead to 

permanent blindness. This is why as a person ages, their vision becomes progressively worse. 

A protective measure against ROS is the use of antioxidant treatments. Antioxidants can be used to 

slow the rate of retinal degradation by counteracting damage from the reactive oxidative species. The 

body produces some antioxidants endogenously, but they can also be obtained outside of the body. 

They can be found in a variety of antioxidant-rich foods, such as fruits, leafy green vegetables, and 

grains, and can also be obtained through dietary supplements. These include carotenoids like 

beta-carotene, lycopene, and vitamins A, C, and E (NCI, 2014). There are a variety of substances that 

act as antioxidants, like the ones mentioned before, in addition to glutathione, coenzyme Q10, lipoic 

acid, flavonoids, phenols, polyphenols, phytoestrogens, etc., all having different properties and roles 

against ROS (Harvard, 2017). In the case of preventing retinal degradation to improve outcomes in 

terms of vision integrity and function, antioxidants can be employed to protect against the damage from 

reactive oxidative species. However, because of physiological barriers, antioxidants cannot simply be 

taken orally and expected to be able to reach its target, i.e. the retina, to enact its protection. 

 

2. Quercetin 

Quercetin, which has the chemical name of 

2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, is a bioflavonoid aglycone, 

specifically of the flavonol subclass, meaning that it has a 3- hydroxyflavone backbone and lacks 

attached sugars, as shown in Figure 3 (Kelly, 2011). 

 

 

Figure 3. Quercetin Structure 

 



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It is a crystalline solid that has a bright citron yellow color. It is lipophilic and hydrophobic in nature so 

its solubility in water is poor to nonexistent (poor in hot water and entirely insoluble in cold water). A 

way to improve its solubility in water is to convert it to a glycoside. This can be done by replacing one 

of the hydroxyl groups, commonly the one at position 3, with a glycosyl group, which can be any sugar 

such as glucose, rhamnose, or rutinose (see Figure 6). A glycoside group at position 3 is known as 

isoquercitin. The addition of a glycosyl group changes the chemical properties of the drug, including 

solubility, absorption, and in vivo effects. Specifically, the addition of the glycosyl group increases the 

water solubility of quercetin. 

 

3. Materials 

Quercetin was purchased from Tocris Bioscience. Glycerol monostearate and Compritol ATO 888® 

were graciously donated by Gattefossé. Miglyol 812® was purchased from Dr Reddy lab Hyderabad 

India. Tween 80 and methyl-beta-cyclodextrin were purchased from Acros Organic. Poloxamer 188 

was purchased from Spectrum. Glycerin was purchased from PCCA. Acetonitrile and dimethyl 

sulfoxide were purchased from Fisher Chemical. Whole rabbit eye globes were purchased from 

Pel-Freez Biologics. The rabbit eye globes were dissected in lab to collect the corneas for use in the 

permeability studies. 

 

4. Methods 

A. Solid Lipid Nanoparticles 

Quercetin solid lipid nanoparticles, or SLNs, were prepared by probe sonication method. The lipid 

phase was prepared with a solid lipid (0.7% w/v Glycerol monostearate) in combination with 1.3% w/v 

Compritol ATO 888® and heated on a hot plate at 80oC. Quercetin was dissolved in 100 μL of 

dimethyl sulfoxide and added to 2.25% w/v glycerin. This mixture was added to the melted lipid phase. 

The aqueous phase was prepared using 0.75% w/v Tween 80®, Poloxomer 188®, and filtered water 

and heated on the hot plate at 80oC. The aqueous phase was then added to the lipid phase while stirring 

at 600 rpm for 2 minutes. The final concentration of quercetin was 0.1% w/v. The premix was 

homogenized with an Ultra-Turrax® at 16,000 rpm for 3 minutes to form a coarse emulsion. This 

coarse emulsion was then subjected to probe sonication at a 15-second pulse rate for 3 minutes. The 

final emulsion was allowed to cool to form the nanoparticles. 

B. Nanostructured Lipid Carriers 

Quercetin nanostructured lipid carriers, or NLCs, were also prepared by probe sonication method. The 

method is almost exactly the same as that for the SLN formulation, except that the lipid phase was 

prepared with a liquid lipid (0.7% w/v Miglyol 812®) in combination with 1.3% w/v Compritol ATO 

888®, which was then heated on a hot plate at 80oC. Quercetin was dissolved in 100 μL of dimethyl 

sulfoxide and added to 2.25% w/v glycerin. This mixture was then added to the melted lipid phase. The 



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aqueous phase was prepared using 0.75% w/v Tween 80®, Poloxomer 188®, and filtered water and 

heated on the hot plate at 80oC. The aqueous phase was added to the lipid phase while stirring at 600 

rpm for 2 minutes. The final concentration of quercetin was 0.1% w/v. The premix was homogenized 

with an Ultra-Turrax® at 16,000 rpm for 3 minutes to form a coarse emulsion, which was then 

subjected to probe sonication at a 15-second pulse rate for 3 minutes. The final emulsion was allowed 

to cool to form the nanoparticles. 

C. Hot Melt Cast Films 

Quercetin films were prepared by melt-cast method. Polyethylene oxide N10 was used as the matrix 

forming polymer. Quercetin and PEO N10 were mixed via geometric dilution to prepare the physical 

mixture. The drug load in the film was 10% w/w. A 10 mm die was placed over a brass plate and heated 

on a hot plate at 75°C for at least one minute. The physical mixture was poured into the center of the 

die and compressed for a few seconds to form a flat matrix surface. The film was heated on the hot 

plate for an additional minute so that the mixture was completely melted and then removed to cool. 

When completely cooled, the film was cut to collect samples that weighed approximately 8 mg each. 

D. Characterization of Nanoparticles 

Mobile phase of acetonitrile:water (ACN:H2O, 40:60) was prepared. Quercetin was dissolved in 

dimethyl sulfoxide (DMSO) to make a 1 mg/mL stock solution for the standards. Varying volumes of 

the stock solution were diluted with the mobile phase to make standards of the following 

concentrations: 1 μg, 2 μg, 5 μg, 10 μg, and 20 μg. The standards were analyzed using UV analysis at a 

wavelength of 369 nm to determine the light absorbance trend, or calibration curve, of quercetin to 

which the nanoparticle emulsions will be compared. The SLN and NLC formulations were diluted 500 

times with purified water and analyzed using a zetasizer (Malvern Instruments, Ltd.) to determine the 

size, polydispersity index, and zeta potential of the particles. The goal was to have small particle sizes, 

low polydispersity index, and high magnitude of zeta potential for the most stable and homogeneous 

formulation. 

Entrapment efficiency, which is a measure of how much drug is entrapped in the nanoparticles, was 

performed by centrifuging 500 μL of each formulation with a filter for 15 minutes. 100 μL of the 

centrifuged filtrate was drawn, diluted with 900 μL of the mobile phase, and then vortexed to ensure 

thorough and homogeneous mixing. Assay was performed to determine quercetin content in the 

nanoparticles. For each formulation, 100 μL of formulation were added to 900 μL of a mixture of 

DMSO and methanol (50:50) and sonicated for 10 minutes. After sonication, the mixture was 

centrifuged for 15 minutes. From this, 100 μL of the supernatant was drawn and diluted with 900 μL of 

the mobile phase before being vortexed to ensure thorough and homogeneous mixing. All samples 

collected from entrapment efficiency and assays were analyzed in triplicates using HPLC-UV method 

with a Kinetex® 5 μm EVO C18 100 Å LC column (250 x 4.6 mm). 

 



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E. Characterization of Films 

Mobile phase of acetonitrile:water (ACN:H2O, 40:60) was prepared. Quercetin was dissolved in 

dimethyl sulfoxide (DMSO) to make a 1 mg/mL stock solution for the standards. Varying volumes of 

the stock solution were diluted with acetonitrile to make standards of the following concentrations: 1 

μg, 2 μg, 5 μg, 10 μg, and 20 μg. The standards were analyzed using UV analysis at a wavelength of 

369 nm to determine the calibration curve of quercetin to which the film samples will be compared. 

Samples of approximately 8 mg were cut from quercetin films and added to 2 mL of acetonitrile. This 

mixture was then sonicated for 5 minutes until the film was completely dissolved. After sonication, the 

stock was diluted by a factor of 20. All samples were collected and analyzed in triplicates using UV 

analysis at a wavelength of 369 nm. 

F. Permeability Studies 

Release and permeability of quercetin from the nanoparticles were studied using a vertical dialysis 

cassette with a 10,000 Dalton MWCO membrane. Isotonic phosphate buffer saline, or IPBS, was made 

with 5% methyl-beta-cyclodextrin. IPBS served as the receiver medium. 18 mL of IPBS was filled into 

the vial, and 1 mL of formulation was filled into the cassette. Measurements were taken at 15, 30, 60, 

90, 120, 150, and 180-minute time points, at which time 1 mL of the receiver medium was drawn and 1 

mL of IPBS was added into the vial. All samples collected were analyzed in triplicates under 

HPLC-UV method. 

Permeability of quercetin from NLCs and films was studied using fresh rabbit cornea in a side-by-side 

diffusion apparatus, maintained at 34°C using a circulating water bath. IPBS with 5% 

methyl-beta-cyclodextrin was made. Spectra/Por® membrane (10,000 Daltons MWCO) were cut and 

soaked in IPBS for 30 minutes. Side-by-side diffusion cells were set up so that the fresh rabbit cornea 

and Spectra/Por® membrane were sandwiched between the cells. For the film studies, the films were 

cut to approximately 45 mg and wetted with IPBS. They were then sandwiched between the rabbit 

cornea and Spectra/Por® membrane, in the following order: donor cell Spectra/Por® membrane 

quercetin film cornea recipient cell (see Figure 4). 

 



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Figure 4. Side-by-Side Diffusion Apparatus Setup 

Source: Adelli GR, Hingorani T, Punyamurthula N, et al. Evaluation of topical hesperetin matrix film 

for back-of-the-eye delivery. European Journal of Pharmaceutics and Biopharmaceutics 2015; 

92:74-82 

 

Both the donor and recipient cells for the film studies were filled with 3.2 mL of IPBS. For the NLC 

formulations and the control, which was 3 mg of pure quercetin mixed with IPBS, 3.2 mL of each 

formulation were added into their respective donor cells, and 3.2 mL of IPBS were added to the 

recipient cells. Measurements were taken at 30, 60, 90, 120, 150, and 180-minute time points. After 

flushing a few times to mix the receiver medium, 0.6 mL samples were drawn from the recipient cell, 

except for the films, for which samples were collected from both donor and recipient cells, and 0.6 mL 

of IPBS was added to the cells to replace the volume removed. The samples were analyzed in 

triplicates using UV analysis at a wavelength of 369 nm. 

 

5. Result and Discussion 

5.1 Characterizations of Nanoparticles and Films 

The solid lipid nanoparticles demonstrated an average particle size of 65.4 r.nm, polydispersity index of 

0.29, and zeta potential of -12.3 mV. Assay and entrapment efficiency results were 78.4 ± 1.6% and 

90.9 

± 0.3%, respectively. Drug release across the Spectra/Por® membrane was 33.3 ± 1.5%. These 

parameters are summarized below in Table 2. Particle size distribution is shown in Figure 5. 

 

 

 

 

 



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Table 2. Physicochemical Characterization of SLN Formulations 
Parameters Solid Lipid Nanoparticles 

Particle Size (r.nm) 65.4 

Polydispersity Index 0.29 

Zeta potential (m V) -12.3 

Assay 78.4±1.6 

Entrapment Efficiency 90.9±0.3 

%Release across 

Spectra/Por® Membrane 

33.3±1.5 

 

 

Figure 5. SLN Particle Size Distribution by Intensity 

 

The nanostructured lipid carriers demonstrated an average particle size of 46.1 r.nm, polydispersity 

index of 0.18, and zeta potential of -16.2 mV. Assay and entrapment efficiency results were 86.6 ± 

0.2% and 

93.4 ± 0.1%, respectively. Drug release across the Spectra/Por® membrane was 47.1 ± 7.9%. These 

parameters are summarized below in Table 3, and particle size distribution is shown below in Figure 6. 

The comparison of the particle size distributions for the SLN and NLC formulations is shown below in 

Figure 7. 

 

 

 

 

 

 



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Table 3. Physicochemical Characterization of NLC Formulations 

Parameters Solid Lipid Nanoparticles 

Particle Size (r.nm) 46.1 

Polydispersity Index 0.18 

Zeta potential (m V) -16.2 

Assay 86.6±0.2 

Entrapment Efficiency 93.4±0.1 

%Release across Spectra/Por® Membrane 47.1±7.9 

 

Figure 6. NLC Particle Size Distribution by Intensity 

 



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Figure 7. SLN vs. NLC Size Distributions by Intensity 

 

Hot melt cast films demonstrated assay results of 76.3 ± 4.1%. Particle size, polydispersity index, zeta 

potential, and entrapment efficiency are parameters designed more for nanoparticle systems and were 

not evaluated with the hot melt cast films. Drug release across Spectra/Por® membranes was also not 

evaluated with the films. 

 

5.2 Corneal Permeability Studies 

All samples were analyzed via UV analysis at a wavelength of 369 nm, at which the standard 

calibration curve had an R2 value of 0.9989. TGA data indicated that physical mixtures were stable 

under the utilized processing temperature. Permeability across the rabbit cornea for quercetin films, 

NLCs, and control are shown in Figures 8, 9, and 10, respectively. 



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Figure 8. Permeability of Quercetin Films 

 

 

Figure 9. Permeability of Quercetin NLCs 



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Figure 10. Permeability of Quercetin Control 

 

The results from the permeability studies, in terms of rate, flux, and permeability, are summarized in 

Table 4 and Figure 11. Transcorneal flux, which is the amount of drug that crosses the cornea per 

minute per area squared (in this case, the area of the cornea is 0.636 cm), of quercetin control, NLCs, 

and films were 0.026 ± 0.002, 0.036 ± 0.006, and 0.144 ± 0.009, respectively. Permeability was 

calculated as flux normalized by assay. 

 

Table 4. Results for Permeability Studies (Rate, Flux, Permeability) 

 Rate (µg/min) Flux (µg/min/cm2) Permeability X 106 (cm/sec) 

Control 0.0165±0.002 0.0260±0.002 0.135±0.012 

NLCs 0.0227±0.004 0.0357±0.006 0.186±0.030 

Films 0.1435±0.006 0.1435±0.009 0.747±0.047 



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Figure 11. Transcorneal Permeability of Quercetin in Different Formulations 

 

The goal parameters for the nanoparticle formulations were to have small particle sizes, low 

polydispersity index, and high magnitude of zeta potential. Both the solid lipid nanoparticles and the 

nanostructured lipid carriers successfully met and fit well within these goal parameters. Particle sizes 

for both formulations were well below 500 nm. The peak of the particle size distribution for the 

NLC formulation was higher and narrower compared to the peak for the SLN formulation, as the 

intensity was noticeably greater and the particle sizes were less variable. Polydispersity indices for both 

were close to zero (0), which is the most ideal polydispersity index in order to have a completely 

uniform formulation. Zeta potentials for both were relatively high in magnitude as well (between -10 

and -20 mV). Both entrapment efficiencies were at least 90% or higher. Drug releases across the 

Spectra/Por® membrane for both formulations, on the other hand, were relatively low (around 30-50%). 

When comparing assays for all three formulations (SLNs, NLCs, and films), film assay results were the 

lowest (by 2%), and NLCs were the highest (by about 8%), with SLNs in between the two. In all 

regards, the NLC formulation had better physicochemical characteristics compared to the SLN 

formulation. This is due to the nature of the lipid matrix shells of the nanoparticles. Because solid lipid 

nanoparticle formulations use only solid lipids, the matrix shells are completely solid and continuous, 

which has limited permeability. Not only does this affect how much drug can be encapsulated in the 

nanoparticles, but it also affects how the drug diffuses out of the nanoparticles. Specifically, this 

structure results in a relatively low drug load, limited drug release, and drug expulsion during storage. 

With nanostructured lipid carriers, on the other hand, the incorporation of a liquid lipid to the solid lipid 



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matrix results in a disrupted and highly permeable nanoparticle shell. This structure allows for a higher 

drug load, greater drug release, and long term drug stability. Thus, from these differences (summarized 

in Figure 12), we would expect to see that the NLC formulation would show better characteristics than 

the SLN formulation, which it did. 

 

 
Figure 12. Advantages of NLC Structure over SLN Structure 

Source: Beloqui A, Solinis MA, Rodríguez-Gascón A, Almeida AJ, Préat V. Nanostructured lipid 

carriers: promising drug delivery systems for future clinics. Nanomedicine: Nanotechnology, Biology 

and Medicine 2016; 12:143-161 

 

To compare how well quercetin permeates from the hot melt cast film across corneas as opposed to 

permeation from the nanoparticles, we used a control of pure quercetin in addition to the NLC 

formulation, which was chosen because it demonstrated better parameters and physicochemical 

characteristics compared to the SLNs. The three main parameters tested in the permeability studies 

were rate, flux, and permeability. Rate was determined by how much drug, in micrograms (μg), crossed 

the cornea from the donor to the receiver cells, per minute, with concentrations extrapolated from the 

calibration curve based on the absorbance of the samples. The rate of drug release permeation for the 

control was the slowest, and the rate for the films was the highest by a significant margin (7-14x 

higher), with the rate of the NLCs in between the two. Flux was calculated as the amount of drug in 

micrograms that crosses the cornea per minute per area squared (area = 0.636 cm). Again, the flux for 

the control was the lowest, and the flux for the films was the highest by a good margin (4-5x higher). 



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Flux for NLCs was in between the other two flux values. Lastly, permeability was calculated as flux 

normalized by assay and reported as centimeters per second. These results showed the same trends as 

with the other two parameters. The permeability of the control across the cornea was the lowest, the 

permeability of the drug from the NLCs was second highest, and the permeability of the drug from the 

films was the highest, once again by a good margin (4-6x higher). In total, both formulations (NLCs 

and films) were more successful compared to the control in drug permeability across the cornea. 

However, the hot melt cast film formulation showed significantly better parameters in all respects 

compared to both the control and the NLC formulation. 

 

References 

Abraham, M., & Acree, W. (2014). On the solubility of quercetin. Journal of Molecular Liquids, 197, 

157-159. 

Adelli, G. R., Balguri, S., & Majumdar, S. (2015). Effect of cyclodextrins on morphology and barrier 

characteristics of isolated rabbit corneas. AAPS PharmSciTech, 16, 1220-1226. 

Adelli, G. R., Hingorani, T., & Punyamurthula, N. (2015). Evaluation of topical hesperetin matrix film 

for back-of- the-eye delivery. European Journal of Pharmaceutics and Biopharmaceutics, 92, 

74-82. 

Aditya, N. P., Macedo, A. S., & Doktorovova, S. (2014). Development and evaluation of lipid 

nanocarriers for quercetin delivery: A comparative study of solid lipid nanoparticles (sln), 

nanostructured lipid carriers (nlc), and lipid nanoemulsions (lne). LWT—Food Science and 

Technology, 59, 115-121. 

Balguri, S. P., Adelli, G. R., & Majumdar, S. (2016). Topical ophthalmic lipid nanoparticle formulations 

(sln,nlc) of indomethacin for delivery to the posterior segment ocular tissues. European Journal of 

Pharmaceutics and Biopharmaceutics, 109, 224-235. 

Beloqui, A., Solinis, M. A., Rodríguez-Gascón, A., Almeida, A. J., & Préat, V. (2016). Nanostructured 

lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine: Nanotechnology, 

Biology and Medicine, 12, 143-161. 

Bentz, A. B. (2009). Review of quercetin: chemistry, antioxidant properties, and bioavailability. 

Journal of Young Investigators. 

Crowley, M., Feng, Z., & Martin, C. (2007). Pharmaceutical applications of hot-melt extrusion: Part I. 

Drug Development & Industrial Pharmacy, 33(9), 909-926. Business Source Complete, Ipswich, 

MA. 

Dan, N. (2016). Compound release from Nanostructured Lipid Carriers (NLCs). Journal of Food 

Engineering, 171, 37-43. 

Dhawan, S., Kapil, R., & Singh, B. (2011). Formulation development and systematic optimization of 

solid lipid nanoparticles of quercetin for improved brain delivery. Journal of Pharmacy and 



www.scholink.org/ojs/index.php/eshs              Education, Society and Human Studies             Vol. 3, No. 1, 2022 

 
25 

Published by SCHOLINK INC. 

Pharmacology, 63, 342-351. 

Douroumis D. (2012). Hot-Melt Extrusion: Pharmaceutical Applications. Oxford: John Wiley & Sons, 

Incorporated. 

Ehrlich, S. D. (2015). Quercetin. University of Maryland Medical Center. Retrieved March 27, 2017, 

from http://umm.edu/ health/medical/altmed/supplement/quercetin 

Flavonoids. (2017). Wako Laboratory Chemicals. Retrieved March 27, 2017, from 

http://www.wako-chem.co.jp/english/labchem/ product/life/Flavonoid/index.htm 

Gaudana, R., Ananthula, H. K., Parenky, A., & Mitra, A, K. (2010). Ocular drug delivery. The AAPS 

Journal, 12(3), 348-360. 

Harvard, T. H. (2017). Chan. Antioxidants: Beyond the hype. Retrieved March 27, 2017, from 

https://www.hsph.harvard.edu/nutritionsource/antioxidants/#age-related%20eye%20disease%20an

d%20antioxidants 

He, Y., He, Z., He, F., & Wan, H. (2012). Determination of quercetin, plumbagin and total flavonoids in 

drosera peltata smith var. glabrata y.z.ruan. Pharmacognosy Magazine, 8(32), 263-267. 

Hippalgaonkar, K., Adelli, G. R., & Hippalgaonkar, K. (2013). Indomethacin-loaded solid lipid 

nanoparticles for ocular delivery: Development, characterization, and in vitro evaluation. Journal 

of Ocular Pharmacology & Therapeutics, 29(2), 216-228. 

Kaufman, P. L., Alm, A., & Levin, L. A. (2011). Adler’s Physiology of the Eye. Philadelphia: Saunders. 

Kelly, G. S. (2011). Quercetin. Alternative Medicine Review, 16, 172-194. 

Kumari, A,, Yadav, S. K., & Pakade, Y. B. (2010). Development of biodegradable nanoparticles for 

delivery of quercetin. Colloids and Surfaces B: Biointerfaces, 80, 184-192. 

Mehnert, W., & Mäder, K. (2012). Solid lipid nanoparticles: production, characterization and 

applications. Advanced Drug Delivery Reviews, 64, 83-101. 

National Cancer Institute. (2017). Antioxidants and cancer prevention. Retrieved March 27, 2017, from 

https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/antioxidants-fact-sheet 

National Eye Institute. (2017). All vision impairment. Retrieved March 27, 2017, from 

https://nei.nih.gov/eyedata/ vision_impaired#1 

National Eye Institute. (2017). Prevalence of adult vision impairment and age-related eye diseases in 

America. Retrieved March 27, 2017, from https://nei.nih.gov/eyedata/adultvision_usa 

National Eye Institute. (2017). Vision impairment tables. Retrieved March 27, 2017, from 

https://nei.nih.gov/ eyedata/vision_impaired/tables 

Prunty, M. C., Aung, M. H., & Hanif, A. M. (2015). In vivo imaging of retinal oxidative stress using a 

reactive oxygen species—activated fluorescent probe. Investigative Ophthalmology & Visual 

Science, 56(10), 5862-5870. 

Quercetin (ab120247). (2017). Abcam. Retrieved March 27, 2017, from 

http://www.abcam.com/quercetin-ab120247.html 



www.scholink.org/ojs/index.php/eshs              Education, Society and Human Studies             Vol. 3, No. 1, 2022 

 
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Published by SCHOLINK INC. 

Quercetin [product insert]. (2016). Ann Arbor, MI: Cayman Chemical Company. 

Repka, M. A., Battu, S. K., & Upadhye, S. B. (2007). Pharmaceutical applications of hot-melt extrusion: 

Part II. Drug Development & Industrial Pharmacy [serial online], 33(10),1043-1057. 

Salunkhe, V. R., & Patil, S. J. (n.d.). UV spectrophotometric and hplc method development of quercetin 

and curcumin in polyherbal churna and its validation. International Journal of Pharmaceutical 

and Phytopharmacological Research, 1-16. 

Srirangam, R., Hippalgaonkar, K., Avula, B., Khan, I., & Majumdar, S. (2012). Evaluation of the 

intravenous and topical routes for ocular delivery of hesperidin and hesperetin. Journal of Ocular 

Pharmacology and Therapeutics [serial online], 28(6), 618-627. 

United Mitochondrial Disease Foundation. (2017). What is mitochondrial disease? Retrieved March 27, 

2017, from https://www.umdf.org/what-is-mitochondrial-disease/ 

Weingerl, V. (2012). A comparative study of analytical methods for determination of polyphenols in 

wine by hplc/uv-vis, spectrophotometry and chemiluminometry. In Macro to Nano Spectroscopy 

(pp. 357-370). Croatia: InTech. 

Wu, T. H., Yen, F. L., & Lin, L.T. (2008). Preparation, physicochemical characterization, and 

antioxidant effects of quercetin nanoparticles. International Journal of Pharmaceutics, 346, 

160-168. 

http://www.umdf.org/what-is-mitochondrial-disease/
http://www.umdf.org/what-is-mitochondrial-disease/

	D. Characterization of Nanoparticles
	F. Permeability Studies

