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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5936_Библиотеки_им_академика_М_И_Перельмана
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278 Golnar Bayatani et al.
https://t.me/medicina_free
In contrast to Gram-negative bacteria, which lack an additional outer membrane
layer, the antimicrobial analyses show that -Fe
and CQDs@-Fe2O3are hazardous to
2O3
the chosen microorganisms. The samples also showed long-lasting antibacterial action
against Gram-positive bacterial strains. It was determined that the preferred mechanism of bactericidal activity of hematite-based thin films is both the penetration of iron
cations into the bacteria cell via their membrane and the generation of reactive oxygen
species based on the results of the antibacterial activity of -Fe2O3 and CQDs@-Fe2O3
under dark and light irradiation conditio ns. These results imply that CQDs@-Fe2O3
nanoparticles can aid in the development of visible-light antimicrobial materials for
their potential bactericidal uses [28].
Green synthesis of multifunctional carbon dots
This study is done by Aharon Gedanken et al. and published in Nanomaterials journal.
By using a simple one-step hydrothermal process, CDs were extracted from medicinal
turmeric leaves (Curcuma longa) and tested for their bactericidal effects on two Gramnegative (E. coli, Klebsiella pneumoniae) and two Gram-positive (S. aureus, S. epidermi-
dis) bacteria. The average size of the CDs was 2.6 nm, and they had spherical forms
(Figure 12.12). Spectra of UV absorption reveal a distinctive peak at 288 nm [29–31].
Figure 12.12: Mean particle size of 2.6 nm on average (b) [31].
The CDs were shown to be superior at killing Gram-positive S. aureus and S. epidermidis bacteria as well as Gram-negative E. coli and K. pneumoniae bacteria. For E. coli
and S. aureus,theMICis0.25mg/mL;forK. pneumoniae and S. epidermidis,itis
0.5 mg/mL. Figure 12.13a,b shows that CDs effectivity at inhibiting the growth of E. coli
and S. aureus within 8 h at 0.25 mg/mL and at 0.5 mg/mL for K. pneumoniae and S.
Chapter 12 Carbon dots in antibiosis: disinfection and sterilization 279
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epidermidis. However, following a 24-hour incubation with 1 mg/mL of the CDs, the
entire eradication of bacterial cells was seen (Figure 13c, d) [31].
The findings showed that the CDs responded qu ickly to growth inhibition of E.
coli and S. aureus with low concentration and short incubation times. But K. pneumoniae and S. epidermidis showed a substantially longer incubation period before being
completely eliminated. Our manufactured CDs displayed improved antibacterial activities against all four p athogens without any atom passivation. Deme thoxycurcumin
and bisdemethoxycurcumin are two important chemicals that are partially retained
inside or on the surface of CDs, enhancing their ability to kill bacteria [31].
(a)
10
10
10
CFU/mL
10
(c)
CFU/mL
8
7
6
5
0 0.25 0.5
8
10
7
10
6
10
5
10
0 0.25 0.5
E.coli
Concentration (mg/mL)
K.pneumoniae
Concentration (mg/mL)
1.0
1.0
8 h
24 h
8 h
24 h
(b)
CFU/mL
(d)
CFU/mL
8
10
7
10
6
10
5
10
0 0.25 0.5
S.aureus
1.0
8 h
24 h
Concentration (mg/mL)
8
10
7
10
6
10
5
10
0 0.25 0.5
S.epidermitis
1.0
8 h
24 h
Concentration (mg/mL)
Figure 12.13: The illustrates the bactericidal effects of CDs on (a) E. coli, (b) S. aureus, (c) K. pneumoniae,
and (d) S. epidermitis [31].
The standard MTT colorimetric test was used to assess the cytotoxicity of CDs in water.
In order to determine if CDs are naturally cytotoxic, The PC-3 cell line was also used for
the cell viability experiment. After a 24-hour incubation period, cell survival was still
more than 95% even at a CDs concentration of 200 g/mL. However, after a 24-hour incubation, CDs at 500 g/mL decreased cell viability by 50% [31].
280 Golnar Bayatani et al.
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Our discovery might open the way for the production of naturally produced CDs
from turmeric leaves as a potential novel antibacterial agent.
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[31] Saravanan A, et al. Green synthesis of multifunctional carbon dots with antibacterial activities.
Nanomaterials. 2021, 11(2), 369.
https://t.me/medicina_free
Nicole Remaliah Samantha Sibuyi✶, Anelisiwe Mbengashe,
https://t.me/medicina_free
Zimkhitha Bianca Nqakala, Antoinette Alliya Ajmal, Tswellang Mgijima,
Cate Malope Mashilo, Aluwani Matshaya, Samantha Meyer,
Mervin Meyer, Martin Opiyo Onani, Abram Madimabe Madiehe
and Adewale Oluwaseun Fadaka
✶
Chapter 13
Carbon dots in drug delivery
Abstract: Drug delivery is an important aspect of any successful disease therapy; it en-
sures that the drugs reach the target site in its intact form and selectively infer its activity with reduced adverse effects on the surrounding tissues. However, selectivity and
drug solubility has always been a major limitation for most therapeutic drugs. To overcome these limitations, drug delivery strategies have been devised, which include chemical modification of the drugs or the use of drug delivery systems (DDS). Although DDS
are able to increase drug solubility and bioavailability based on their drug target and
route of administration, they can be limited by several factors such as bystander toxicity,
early drug release and clearance. In recent years, the focus has shifted to nanocarriers
due to their unique physicochemical properties. Carbon dots (CDs), in particular, stand
out as they are made from carbon sources and are perceived to be biocompatible. Furthermore, their smaller sizes (2–5 nm) afford them a tunable photoluminescence and
fluorescent properties that can help monitor CD–drug conjugates in real time.
Keywords: Carbon dots, drug delivery, drug loading, drug monitoring, nanocarriers,
tracking agents
✶
Corresponding authors: Nicole Remaliah Samantha Sibuyi, Department of Science and Innovation
(DSI), Mintek Nanotechnology Innovation Centre (NIC), Advanced Materials Division, Health Platform,
Mintek, Randburg, South Africa; DSI/Mintek NIC Biolabels Node, Department of Biotechnology,
University of the Western Cape, Bellville, South Africa
✶
Corresponding authors: Adewale Oluwaseun Fadaka, DSI/Mintek NIC Biolabels Node, Department
of Biotechnology, University of the Western Cape, Bellville, South Africa; Department of Anesthesia,
Division of Pain Management, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA;
School of Medicine, Southern Illinois University, 801 N. Rutledge, Springfield, IL 62702
Anelisiwe Mbengashe, Antoinette Alliya Ajmal, Cate Malope Mashilo, Aluwani Matshaya,
Mervin Meyer, Abram Madimabe Madiehe, DSI/Mintek NIC Biolabels Node, Department
of Biotechnology, University of the Western Cape, Bellville, South Africa
Zimkhitha Bianca Nqakala, Tswellang Mgijima, Martin Opiyo Onani, Organometallics and
Nanomaterials, Department of Chemical Sciences, University of the Western Cape, Bellville, South Africa
Samantha Meyer, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape
Peninsula University of Technology, Bellville, South Africa
https://doi.org/10.1515/9783110799958-013
284 Nicole Remaliah Samantha Sibuyi et al.
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13.1 Introduction
Most drugs fail to reach their full therapeutic potential mainly due to their adverse bystander effects and low bioavailability [1]. These limitations, to some extent, were resolved through the use of conventional drug delivery systems (DDS), which had shown a
significant improvement in the efficacy of the drugs through various modes of administration [2]. However, the DDS can be limited by poor bioavailability, fast drug metabolism, early drug release, early drug clearance, and poor permeability [1, 3]. Nanocarriers
are among the advanced DDS that were explored in order to overcome the shortcomings
of the conventional DDS. The nanomaterials present unique physicochemical properties
that can be easily manipulated to produce stimuli-responsive DDS [4] for targeted and
controlled drug release [5]. Nanocarriers are ideal DDS, as they are biocompatible, are
non-cytotoxic, and have a prolonged residence time [6]. Moreover, their small size allows
them to move freely within the diseased tissues without a need for a targeting moiety [7].
Various organic and inorganic nanoparticles (NPs) showed potential; however, the
chapter focuses on the carbon dots (CDs) as an innovative tool for drug delivery.
The role of CDs as DDS for various diseases is receiving an enormous attention in
recent years. Their ability to target drugs and monitor their circulation and localization
brings a fresh perspective to drug delivery [3] and disease therapy [8]. Their outstanding
optical, non-toxic, and size-based properties are a promising platform that can allow the
CDs to be built into multifunctional systems for biomedical applications. The carbonbased CDs are more especially appealing due to their photostable fluorescent properties
which can be used to track their mobility and activity when used in vivo [3, 9]. Moreover, the CDs are versatile and present an opportunity to load and/or encapsulate bioactive materials onto them; that way they can be developed into multiplex systems [3, 10].
The chapter discusses the feasibility of the CDs as drug delivery agents, starting with the
conventional DDS and their limitations. The attributes that make CDs as potential drug
delivery agents are also highlighted, together with the strategies that are used to load
and encapsulate the drugs. In addition to their application as drug delivery agents, the
tunable photoluminescence (PL) and fluorescent properties of the CDs can be employed
to monitor drug response in real time. The possible biosafety of CDs can be improved
by developing smart and stimuli-responsive CD DDS.
13.2 Conventional DDS and their limitations
Non-specificity, biodegradation, and solubility are the major limitations of the current
drugs, resulting in insufficient dose reaching the pathological tissues, and thus reduced drug efficacy. Using higher doses to increase the amount of drugs that reach
the target tissues is usually associated with adverse bystander effects. Strategies have
been devised to reduce the side effects of the drugs, by delivering the drugs directly at
Figure 13.1: Type of drug formulations and routes of their administration (reprinted with permission
https://t.me/medicina_free
from MDPI [2]).
Chapter 13 Carbon dots in drug delivery 285
286 Nicole Remaliah Samantha Sibuyi et al.
https://t.me/medicina_free
the target site [2, 3, 11] through the use of DDS. The con ventional DDS are based on
drug formulations such as tablets, capsules, powders, syrups, ointments, lotion, and
droplets, which are inspired by the drug solubility, half-life, permeability, pharmacokinetics, and route of administration. Typical routes for drug administration are
shown in Figure 13.1, which takes into account the characteristic behaviour of the
drug within the body and the drug target. Oral administration can subject the drugs
to degradation by digestive enzymes and the low pH in the stomach, resulting in less
amount of drugs reaching the diseased tissues [12, 13], while the parenteral administration route can have 100% bioavailability and drug targeting [2]. The efficiency and
potency of a drug is highly dependent on its bioavailability, as well as the drug’s ability to escape biodegradation by digestive enzymes or at acidic pH, and early drug
clearance [1]. The conventional DDS are able to deliver the drugs at disease sites; however, most, if not all, of these systems have several disadvantages listed in Table 13.1,
such as bystander toxicity, early drug release, early drug clearance, and poor solubility that limit their application as drug delivery agents [3].
Table 13.1: Attributes and limitations of the conventional DDS.
DDS route of
administration
Oral Drug administration by
Injectable Used for drugs with
Application Advantages Limitations References
tablets
short half-life
Cost-effective
Ease of large-scale
production
Long shelf life
Ease of
administration
Can be used for
unconscious and
comatose patients
Concentration of
drug needed is low
Rapid absorption of
drug
No risk of
degradation of drug
Degradation by
digestive enzymes and
gastric juices
Effect of the drug may
sometimes be too slow
for emergencies
Low bioavailability,
some of drugs
absorbed in nontargeted sites
Not useful for
unconscious patients
Pain at the injection site
Risk of embolism
[, ]
[]
[]
Table 13.1 (continued)
https://t.me/medicina_free
Chapter 13 Carbon dots in drug delivery 287
DDS route of
administration
Transdermal A topical DDS using
Pulmonary Drugs administered
Drug carrier Incorporating and
Application Advantages Limitations References
patches and through a
percutaneous
absorption
Drugs are released to
the blood stream in a
controlled manner
through mouth or nose
inhalation
encapsulating drugs or
therapeutic agents
Frequency of dosing
is reduced
Bioavailability is
improved
Flexibility in
terminating drug
administration
Useful for potent
drugs
Requires small doses
Onset effect
Adverse effects are
less severe
Drugs are delivered
to target organ
Enhance the
efficiency,
bioavailability, and
efficiency of drugs
Reduces frequency of
administration
Simplified
administration
ensures patient
compliance.
Minimizes drug side
effects
Skin irritation on the
site of application
Limited number of
drugs that can be used
due to skin permeability
Performed by health
professionals
Airways should be
accessible
Can cause irritation of
airways
Possible toxicity
Difficulty scaling-up
production
[]
[]
[]
[, ]
The attributes that had made DDS to be successful drug delivery agents are also
highlighted in Table 13.1; however, for the drugs to successfully execute their therapeutic effects they must also overcome unfavourable physiological barriers. Development
of new drugs is time consuming and expensive; hence, the use of DDS can improve the
efficacy of pre-existing drugs. Drug carriers are engineered for targeted and controlled
drug release in the target cells to enhance drug potency, safety, bioavailability [18], and
improved patient compliance. An appropriate drug carrier should be biocompatible,
biodegradable, and highly soluble, and the most important feature is their ability to
transport the drug in a targeted manner. There are many strategies reported for drug
delivery; however, drug delivery must work synergistically with the drug release profile
for enhanced therapeutic effect. Nanomaterials with special focus on CDs as discussed
in this chapter emerged as a viable approach for targeted drug delivery.
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