Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5401_Библиотеки_им_академика_М_И_Перельмана.pdf
304 Herbal Pharmacopeia
65. Li W, Lee MK. Antiapoptotic property of human α-synuclein in neuronal cell lines is associated with the
inhibition of caspase- 3 but not caspase- 9 activity. J. Neurochem. 2005;93(6):1542–1550.
66. Gunasekaran R, Narayani RS, Vijayalakshmi K, Alladi PA, Shobha K, Nalini A, et al. ‘Exposure to
cerebrospinal uid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel
expression in rat spinal motor neurons. Brain Res. 2009;1255:170–179.
67. Ge P, Luo Y, Wang H, Ling F. Anti- protein aggregation is a potential target for preventing delayed neuro-
nal death after transient ischemia. Med. Hypotheses 2009;73(6):994–995.
68. Sinclair HL, Andrews PJ. Bench- to- bedside review: hypothermia in traumatic brain injury. Crit. Care
2010;14(1):204.
69. Bhattacharya SK, Chakrabarti A, Chatterjee SS. Activity proles of two hyperforin- containing Hypericum
extracts in behavioral models. Pharmacopsychiatry 1998;31;Suppl 1:22–29.
70. Watanabe CM, Wolffram S, Ader P, Rimbach G, Packer L, Maguire JJ, et al. The in vivo neuromodula-
tory effects of the herbal medicine ginkgo biloba. Proc. Natl. Acad. Sci. USA 2001;98(12):6577–6580.
71. Maitra I, Marcocci L, Droy- Lefaix MT, Packer L. Peroxyl radical scavenging activity of Ginkgo biloba
extract EGb 761. Biochem. Pharmacol. 1995;49(11):1649–1655.
72. Galasso C, Orece I, Pellone P, Cirino P, Miele R, Ianora A, Brunet C, Sansone C. On the neuroprotective
role of astaxanthin: new perspectives?. Mar. Drugs 2018 Jul 24;16(8):247.
73. Agarwal A, Malini S, Bairy K, Rao MS. Effect of Tinospora cordifolia on learning and memory in normal
and memory decit rats. Indian J. Pharm. 2002;34:339–349.
74. Nadkarni K Indian plants and drugs with medicinal properties and uses. Madras: Norton and Co., India;
1908.
75. Damodaran M, Ramaswamy R. Isolation of l- 3:4-dihydroxyphenylalanine from the seeds of Mucuna
pruriens. Biochem. J. 1937;31(12):2149–2152.
76. Vaidya AB, Rajagopalan TG, Mankodi NA, Antarkar DS, Tathed PS, Purohit AV, et al. Treatment of
Parkinson’s disease with the cowhage plant- Mucuna pruriens Bak. Neurol. India 1978;26(4):171–176.
77. Venturi VM, Piccinin GL, Taddei I. Pharmacognostic study of self- sown Galanthus nivalis (var. gracilis)
in Italy. Boll. Soc. Ital. Biol. Sper. 1965;41(11):593–597.
78. Wilcock GK, Lilienfeld S, Gaens E. Efcacy and safety of galantamine in patients with mild to moderate
Alzheimer’s disease: multicentre randomised controlled trial. Galantamine International- 1 Study Group.
BMJ 2000;321(7274):1445–1449.
79. Alghamdi BS. The neuroprotective role of melatonin in neurological disorders. J. Neurosci. Res. 2018
Jul;96(7):1136–1149.
80. Bhattacharya SK, Kumar A, Ghosal S. Effects of glycowithanolides from Withania somnifera on an
animal model of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats.
Phytother. Res. 1995;9(2):110–113.
81. Bhattacharya A, Ghosal S, Bhattacharya SK. Anti- oxidant effect of Withania somnifera glycowithano-
lides in chronic footshock stress- induced perturbations of oxidative free radical scavenging enzymes and
lipid peroxidation in rat frontal cortex and striatum. J. Ethnopharmacol. 2001;74(1):1–6.
82. Siddiqui AN, Siddiqui N, Khan RA, Kalam A, Jabir NR, Kamal MA, Firoz CK, Tabrez S. Neuroprotective
role of steroidal sex hormones: an overview. CNS Neurosci. Ther. 2016 May;22(5):342–350.
83. Ambikar DB, Harle UN, Khandare RA, Bore VV, Vyawahare NS. Neuroprotective effect of hydroalco-
holic extract of dried fruits of Trapa bispinosa Roxb on lipofuscinogenesis and uorescence product in
brain of D- galactose induced ageing accelerated mice. Indian J. Exp. Biol. 2010;48(4):378–382.
Safety Assessment of
14
Nanoparticle- Based Herbal
Formulations
Haris Khan, Sumiya Mustafa Alvi, Muhammad Ibrahim Khan,
Hazrat Nabi, and Muhammad Imran Khan
Department of Biomedical Sciences, Pak Austria Fachhochschule:
Institute of Applied Sciences and Technology, Haripur, Pakistan
14.1 INTRODUCTION
Nanotechnology has its applications in various technological and scientic elds, including pharmaceuticals and medicine. The formulations based on nanoparticles are among the promising applications
of nanotechnology in biomedical research [1]. These formulations, referred to as nanomedicines, are
designed to increase the efcacy and delivery of therapeutic agents. In recent years, there has been
growing interest in nanoparticle- based herbal formulations, involving incorporation of nanoparticle
technology into herbal medicine. This approach involves incorporating time- tested efcacy of herbal
medicines with the advance delivery properties of nanoparticles, therefore resulting in formulations
which offers improved targeted delivery, bioavailability, and controlled release of active compounds [2].
For thousands of years, herbal medicine has been an essential part of healthcare systems, used in
various traditional practices. These natural compounds derived from plants are found to have various
therapeutic properties [3]. Despite their signicant potential, the applications of herbal medicines in
clinical practice involves several challenges. Under physiological conditions, numerous active
herbal compounds have rapid metabolism, low bioavailability, poor water solubility, and instability.
Thus, these issues signicantly limit the effectiveness and absorption of herbal compounds and
often require higher doses to produce the desired effect [4]. However, there are numerous unwanted
side effects associated with the usage of high doses of such herbal compounds.
Nanoparticles are very small particles with a size range of 10–100 Nm. Due to their large surface
area and small size, nanoparticles possess unique chemical and physical properties. Nanotechnology
has offered promising solutions to overcome challenges associated with using herbal medications
[5]. Studies have shown that therapeutic effectiveness of herbal medicines can be increased by engineering nanoparticles as their carriers. The properties of nanoparticles make them suitable for delivering the drugs because these properties help nanoparticles interact at molecular and cellular levels
in biological systems [6].
Nanoparticles can be integrated by encapsulation and conjugation to herbal compounds, which
helps in the transport of herbal compounds across biological barriers, protecting them from degradation, and improving their solubility. Moreover, the controlled release of herbal compounds, and the
targeted delivery of herbal compounds, can be ensured by using target specic nanoparticles [7].
14.1.1 T
The incorporation of nanoparticles in herbal medications has shown numerous therapeutic benets, including in various neurological, cardiovascular, and infectious diseases [13]. For instance,
ypes of NaNoparTicles Used iN Herbal formUlaTioNs
305
306 Herbal Pharmacopeia
TABLE 14.1
Different Type of Nanoparticles with Their Composition and Advantages
Type Composition Advantages References
1. Lipid nanoparticles Solid lipid nanoparticles (SLNs),
and nanostructured lipid carriers
(NLCs)
2. Liposomes Lipid bilayer spherical Encapsulating both hydrophobic and
3. Polymeric
nanoparticles
4. Dendrimers Tree- like structures Increasing stability, solubility and targeted
5. Metal nanoparticles Silver, gold, and other metal
Synthetic or natural polymers Reduce dosing frequency and increase
nanoparticles
For encapsulation by providing solid matrix
to lipophilic herbal compounds
hydrophilic herbal compounds.
Increasing the bioavailability of drugs that
have poor solubility
therapeutic efcacy
delivery of compounds
Diagnostic and therapeutic applications [12]
[8]
[9]
[10]
[11]
FIGURE 14.1 Types of nanoparticles used in herbal medications.
curcumin has lower bioavailability when taken orally; however, encapsulating it within nanoparticles signicantly increases the stability, effectiveness, and bioavailability of curcumin [13]. While
nanoparticle- based herbal formulations have numerous benets, several challenges exist for their
development and commercialization processes. These are scalability of nanoparticle production,
regulatory hurdles, potential toxicity, and the necessity for thorough preclinical or clinical evaluations to be conducted. Moreover, there are some complexities that come with herbal medicines
especially due to multiple active compounds they contain, thereby making standardization difcult
[14] (Table 14.1 and Figure 14.1).
14.1.2 imporTaNce of safeTy assessmeNT iN NaNoTecHNology- eNHaNced
Herbal mediciNes
In the development of nanotechnology- incorporated herbal medicines, it is crucial to have safety
assessment in addition to efcacy evaluation. On the other hand, their distinctive nature poses threats
which should be well comprehended and managed. Nanoparticle- based products’ safe proles are
determined by factors like nanoparticles’ physicochemical properties, the nature of encapsulated
herbal compounds and interaction between biological systems with the nanoparticles [15].
Safety Assessment of Nanoparticle-Based Herbal Formulations 307
14.1.2.1 Physiochemical Characteristics and Biological Interactions
These medicines have unique physicochemical characteristics such as small size and large surface
area, as well as the ability to penetrate biological membranes. These features may alter biodistribution and pharmacokinetic behaviors of entrapped herbal substances, hence causing unpredicted
biological reactions. For example, nanoparticles can pass through physiological barriers such as
the blood–brain barrier due to their reduced size which may enhance therapeutic efciency but also
increase the chances of inadvertent accumulation into susceptible tissues [16].
The cellular uptake or endocytosis, hydrophobicity, surface charge, and targeting of ligands all
have impacts upon the nanoparticle’s cellular internalization, distribution, and clearance. Therefore,
it is crucial to understand these interactions to regulate and predict the biological behavior of these
nanoparticles- based formulations [17].
14.1.2.2 Potential Toxicity Concerns
Herbal medicines are typically harmless. However, the incorporation of nanotechnology may raise
new safety issues. Cytotoxicity, oxidative stress, and inammation can be associated with using
nanoparticles due to their high reactivity and capacity for generating ROS. Retaining these particles
in the body leads to their accumulation, thereby enhancing their effects which could result in longterm poisoning [18].
Moreover, toxicity can be inuenced by nanoparticle composition, such as the choice of coating
materials and core. For example, silver or gold metal nanoparticles have been shown to cause cytotoxicity at higher concentrations or upon prolonged exposure. Moreover, some polymeric nanoparticles may degrade into toxic byproducts. Consequently, careful material selection and characterization
is needed for nanoparticle- based formulations [19].
14.1.2.3 Regulatory and Ethical Considerations
The evaluation of safety on nanotechnology- enhanced herbal medicines is not only a scientic and
technical challenge but also an ethical and regulatory issue [20]. Various regulatory agencies globally have recognized the necessity for specic guidelines for assessing the safety and efcacy of
nanomedicines. These guidelines usually entail extensive preclinical and clinical studies inclusive
of toxicological evaluations done to ensure that benets from using nanoparticulate- based formulations outweigh any risks associated with it [21].
Ethically, it is crucial to ensure that these advanced formulations are developed and applied in a
responsible manner. This includes open disclosure of all safety data, full consent from clinical trial
participants, and equal access to the benets of these technologies. Another crucial factor that must
be considered is nanoparticles’ potential environmental impact [22]. Incorporation of nanotechnology into herbal medicine has signicant potential to improve therapeutic efcacy. However, a thorough safety assessment is required to ensure that these developed formulations are both human- safe
and environmentally friendly. As the eld evolves, development efforts and ongoing research must
prioritize optimizing the safety prole of nanoparticle- based herbal products [23]. This chapter
explores more thoroughly the approaches and methodologies used to assess the safety of
nanotechnology- enhanced herbal medicines, emphasizing the importance of taking a balanced and
cautious approach to their development and use.
14.2 PRECLINICAL SAFETY ASSESSMENT
Clinical trials are conducted after the important stage of preclinical safety assessment in the development of nanotechnology- based herbal medicines, which is aimed at identifying any potential risks
associated with such formulations [24]. At this stage both in vitro and in vivo models are employed
to thoroughly investigate the toxicity, pharmacokinetics, and biocompatibility of nanoparticles [25].
The components of preclinical safety assessment are explained in detail below:
308 Herbal Pharmacopeia
14.2.1 iN viTro ToxiciTy TesTiNg
At this stage both in vitro and in vivo models are employed to thoroughly investigate toxicity, pharmacokinetics, and biocompatibility of nanoparticles These studies are performed on cultured cells
and tissues using a variety of parameters, including morphological changes, cell population doubling time and viability. Common techniques include MTT assay and XTT assay, the LDH release
assay, ow cytometry procedure, and comet assay.
Various specialized assays are commonly used in in vitro investigations to evaluate the production of reactive oxygen species (ROS), oxidative stress, and mitochondrial dysfunction. Because of
their affordability, ease of use and capacity to regulate test settings, in vitro assays are an invaluable
resource for preliminary toxicity screening [26].
14.2.2 iN vivo aNimal sTUdies
In vivo animal studies are vital for assessing the systemic toxicity, pharmacokinetics, and overall
safety prole of herbal medicines based on nanoparticles, even while in vitro research offers important preliminary data. In these investigations, the formulations are given to mouse models of animals
and their effects on different physiological systems are observed [27].
In vivo study involves acute and chronic toxicity studies, dose–response studies, and assessment
of organ toxicity.
14.2.3 evalUaTiNg THe pHarmacokiNeTics aNd biodisTribUTioN of NaNoparTicles
In order to understand the absorption, distribution, metabolism, and excretion (ADME) of nanoparticles, pharmacokinetics and biodistribution studies must be considered. Overall, these investigations help us in understanding the body processes that determine what happens to nanoparticles
(Figure 14.2).
Absorption: To determine the bioavailability, the uptake of nanoparticles from the site of
administration, including oral, intravenous, or topical applications, is evaluated.
Distribution: Various imaging techniques, including magnetic resonance imaging (MRI),
positron emission tomography (PET) and uorescence imaging, are commonly used to
determine the movement of nanoparticles in various tissues and organs. Therefore, the sites
of accumulation may be recognized from this study.
Metabolism: Scientists are looking at the metabolic pathways through which nanoparticles
pass through to better understand its biotransformation. This involves determining toxic
metabolites.
Excretion: Elimination routes such as urine, fecal matter or other channels of nanoparticle
removal are analyzed for clearance rate determination and likely deposition sites.
14.2.4 immUNogeNiciTy aNd biocompaTibiliTy TesTiNg
The interaction of nanoparticle- based formulations with the immune system can result in immune
responses that may jeopardize their safety and efciency. Immunogenicity testing considers nanoparticles’ ability to cause allergic, inamed, or immunosuppressive reactions [28].
Cytokine release assays reveal pro- inammatory cytokines produced by immune cells when
exposed to particles, indicating inammation. By contrast, complement activation assay is a test
which determines complement system activation, leading to immune- mediated adverse effects.
Moreover, in vivo immunogenicity studies involve animal models that are used to study the response
of the immune system towards nanoparticles, such as potential anaphylaxis, activation of immune
cells, and production of antibodies. Biocompatibility tests seek to assess how nanoparticles interact
with biological tissues with a view to establishing if they have any harmful consequences [29].
Safety Assessment of Nanoparticle-Based Herbal Formulations 309
FIGURE 14.2 Pharmacokinetics and Biodistribution of Nanoparticles within the body.
14.3 TOXICOLOGICAL PROFILING
This is a complete evaluation of nanoparticle- based herbal medicines to identify, characterize, and
quantify potential toxicities. This process ascertains the safety of these formulations by assessing
their impacts on biological systems at cellular and organismal levels [30].
14.3.1 ideNTificaTioN aNd cHaracTerizaTioN of possible ToxiNs
Possible toxins in nanoparticle- based herbal formulations are associated with the following
parameters:
14.3.1.1 Nanoparticle Components
Materials used for nanoparticle construction (core, coating, functionalization) can be toxic. For
instance, metal nanoparticles may generate oxidative stress and cause cellular impairment [31].
14.3.1.2 Contaminants and Impurities
Toxicity can also result from residual solvents, reagents, or byproducts present during manufacturing [32].
14.3.1.3 Herbal Compounds
Some phytochemicals which are considered safe can show toxicity at high doses or prolonged exposure [33].
Characterization entails detailed analysis of nanoparticle physicochemical properties such as
size, shape, surface charge, and composition by means of transmission electron microscopy (TEM),
dynamic light scattering (DLS), and inductively coupled plasma mass spectrometry (ICP- MS).
310 Herbal Pharmacopeia
Impurities and herbal compounds are identied and quantied using high- performance liquid chromatography (HPLC) and gas chromatography- mass spectrometry (GC- MS).
14.3.2 dose–respoNse relaTioNsHips
Understanding the dose–response relationship is essential. This links the level of exposure with how
degree of toxicity. No observed adverse effect level (NOAEL) and least observed adverse effect
level (LOAEL) are established through dose–response studies [34]. Acute dose–response experiments assess what happens when a large amount is given at once, thus determining the median lethal
dose; that is, where half of the experimental population dies from exposure to this amount [35].
Subacute and subchronic dose–response trials involve repeated administration at various doses over
weeks or months to establish cumulative toxicity and safe dosage ranges [36]. Moreover, there are
in vitro and in vivo tests, which involve the monitoring of physiological, biochemical, histopathological parameters as well as determination of safety margins from collected data for future dosing
schedules on other animals.
14.4 CHRONIC TOXICITY AND CARCINOGENICITY STUDIES
Concerning nanoparticle- based herbal preparations, this test assesses the long- term effects, focussing in particular focusing on potential organ toxicity, physiological changes, and system reactions
which may result from prolonged exposure. Generally, these tests involve repeated dosing of the
formulation to animals over a long period, usually encompassing much of the animal’s life [37].
In chronic toxicity studies, there are key elements that must be considered, including health parameters monitoring, specic organ toxicity assessment, biochemical, and hematological analysis.
Additional studies may be conducted to understand the mechanisms behind observed genotoxic
effects. These studies may investigate oxidative stress, DNA repair mechanisms, and the activation
of specic signaling pathways.
14.4.1 geNoToxiciTy aNd mUTageNiciTy TesTiNg
Genotoxicity and mutagenicity tests assess a substance's ability to damage genetic material, resulting in mutations, chromosomal aberrations, or other genetic alterations. These tests are critical in
determining the carcinogenicity and reproductive safety of nanoparticle- based formulations [38].
In vitro genotoxicity tests include the Ames test (bacterial mutagenicity), the comet assay (DNA
strand breaks), and the micronucleus assay (chromosomal damage in cultured mammalian cells)
[39]. In vivo genotoxicity tests include the bone marrow micronucleus test, which causes chromosomal damage in bone marrow cells, and the dominant lethal test, which detects mutagenic potential
in germ- cells [40].
Genotoxicity and mutagenicity test results assess cancer and genetic disease risk, which helps
with overall toxicological assessment and regulatory safety requirements.Genotoxicity and mutagenicity tests yield critical information for determining the risk of cancer and genetic diseases. They
are an important part of the overall toxicological assessment and are mandated by regulatory agencies to ensure the safety of new formulations [40]. Overall, toxicological proling is an important
aspect for developing safe nanoparticle- based herbal medicines.
14.5 CLINICAL SAFETY ASSESSMENT
Evaluation of the clinical safety for a drug is a very important stage before it can be introduced in
the market for human consumption. It includes phases of clinical trials, adverse effects monitoring,
long- term safety evaluation, and drug surveillance. Different methods and safety protocols must be
Safety Assessment of Nanoparticle-Based Herbal Formulations 311
followed in clinical safety trials to ensure the maximum safety and efcacy of the drug [41]. In this
section, we will discuss the clinical safety assessment procedures and protocols for nanoparticlebased herbal formulation.
14.5.1 pHases of cliNical Trials for NaNoparTicle- based Herbal formUlaTioN
Clinical trials give us the information and data for the safety, efcacy, and effectiveness of treatments. They are categorized by their purpose, different phases, and design of trials. Clarifying the
study question and population, identifying treatment and comparison groups, selecting methods for
treatment group allocation, clarifying primary and secondary outcomes, power analyses, analytic
plans, and reporting of results are all important parts of a clinical trial design. Nanoparticle- based
herbal formulations involve ve phases [42]. These phases are explained in Table 14.2.
14.5.2 moNiToriNg adverse effecTs aNd loNg- Term safeTy iN HUmaN sUbjecTs
Monitoring the adverse effects and long- term safety of a drug in humans is very crucial and a stepby- step process [46]. Several methodologies and procedures are designed to collect and analyze
data. Here, we will discuss this process in detail.
14.5.2.1 Initial Reporting Systems
Initially, any adverse effect is reported by physicians, pharmacists, or other healthcare professionals who play an important role in the identication and reporting of adverse effects associated with
herbal drugs [46]. Patients using herbal medicines can also report any adverse effects they experience on government or healthcare authorities’ given platforms.
14.5.2.2 Clinical Monitoring
After an herbal drug is distributed in the market, post- approval clinical trials (Phase 4) are conducted
to gather more data on its safety prole. In these trials, we can identify less common adverse effects
that may not have been seen in earlier phase trials due to smaller sample sizes [45]. In these studies, a group of patients are monitored who are taking the herbal drug and their health outcomes are
compared to a control group not using the drug [47].
TABLE 14.2
Description for Clinical Trial Phases
Phases for
Clinical Trials Purpose Number and Type of Patients
Phase 0 To gather primary data about the new compound and how it affects the
subjects.
Phase 1 To assess and evaluate the short- term safe dosage value, tolerability,
clinical pharmacology, pharmacokinetics, and pharmacodynamics of
the new compound.
Phase 2 To check the effects and efcacy of the drug on different subjects and
determine the effective and safe dosage ranges.
Phase 3 To check dosage impact, efcacy, and any adverse effects and ensure its
safety on a larger scale [44].
Phase 4 To check the long- term positive and adverse effects and other
indications are monitored with the passage of time [45].
10–15 healthy volunteers [43]
50–100 healthy volunteers or
patients [43]
100–300 patients with the
targeted disease [43]
Up to 1000 patients with the
targeted disease [43]
Thousand or million patients
with the targeted disease [43]
312 Herbal Pharmacopeia
14.5.2.3 Pharmacovigilance Networks
Several healthcare organizations initiate programs for collecting data monitoring the reports of
adverse events [48]. These include, for example, the WHO’s International Drug Monitoring Program,
which collects and analyzes data on adverse effects reported globally. These databases help us identify different patterns and signals that might indicate a safety issue with a particular herbal drug.
14.5.2.4 Regular Safety Updates
It is necessary for manufacturers and producers of different herbal drugs to regularly submit safety
updates about products to the health regulatory authorities. These updates include all known data on
adverse effects and new safety information gathered since the drug was last reviewed [49]. There are
also risk management plans (RMP) that clearly state how the manufacturer intends to monitor the
risks associated with the herbal drug, including strategies made for long- term safety monitoring [50].
14.5.2.5 Post- Marketing Studies
These studies are used to observe the effects of the herbal drug in real- world scenarios over a prolonged period. It includes large populations and is benecial for the detection of rare or long- term
adverse effects [51]. There are different patient registries designed for specic diseases or treatments. These registries can provide real- time data on the safety and effectiveness of herbal drugs
used to treat those conditions [52].
14.5.2.6 Pharmacogenomics Studies
In these studies, scientists analyze how genetic differences among patients affect their response to
herbal drugs. This study can help us in the identication of those patients who are at higher risk for
adverse effects. In this way, more personalized and safer use of herbal medicines can be given to
them [53].
14.5.3 posT- markeT sUrveillaNce aNd pHarmacovigilaNce
As discussed above in sections 5.2.5 and 5.2.6, these studies are essential for the long- term evaluation of drug’s adverse effects and to analyze how different responses of herbal drugs are generated
among different patients because of the individuals’ genetic dissimilarities.
14.5.3.1 Real- World Evidence Collection
Data from electronic health records (EHR) is analyzed to check and monitor the effects of herbal
drugs on a large scale. This includes the tracking of patient outcomes, adverse effects, and their
interactions with other medications.
14.5.3.2 Active Surveillance Programs
Specic populations known to use certain herbal drugs is surveyed regularly to gather detailed
information of their experiences and any adverse effects. Healthcare facilities can be set up as sites
to monitor and report on the use and effects of herbal drugs [54].
14.5.3.3 Signal Detection
Advanced algorithms and data mining techniques should be used to analyze large datasets from various sources to detect signals indicating potential adverse effects.
14.5.3.4 Risk Communication
When a new risk is detected, regulatory authorities issue safety alerts to healthcare providers and the
public, advising on the risks and recommending actions to mitigate them.
Safety Assessment of Nanoparticle-Based Herbal Formulations 313
Advance Imaging and
Genotoxicity Screening
14.5.3.5 Regulatory Actions
Based on new safety information, regulatory authorities may require updates on the labeling of
herbal drugs to include warnings about the potential adverse effects. In cases in which the risks of
an herbal drug outweigh its benets, regulatory authorities announce the withdrawal of drug from
the market to protect public health [55].
14.6 ANALYTICAL TECHNIQUES FOR SAFETY ASSESSMENT
Analytical techniques give us detailed insights into the characterization, behavior, aggregation, distribution, adsorption, and degradation of nanoparticles in biological environments. Thus, analytical
techniques are essential for the assessment of safe nanoparticle- based herbal formulations [56]. To
assess the safety of nanoparticle- based herbal formulations, advanced imaging and spectroscopy
techniques are used such as TEM or SEM. For nanoparticle tracking and quantication, methods
such as DLS is used and for surface characterization and stability analysis techniques like X- ray
Photoelectron Spectroscopy (XPS) were employed (Figure 14.3).
14.6.1 advaNced imagiNg aNd specTroscopy meTHods
It is essential to characterize the specialized nanoparticles to access the nano- bio interactions and
for this advanced imaging and spectroscopic techniques are used. These techniques offer comprehensive knowledge of the structural, functional and compositional characteristics of nanoparticles
which assists us in better understanding of their behavior, interaction, and possible toxicities within
the biological systems [57]. It is necessary to establish different analytical techniques for the identifying of nanomaterials in accordance with the recommendations of European Commission.
FIGURE 14.3 Various analytical techniques used for safety assessment of nanoparticles.
spectroscopy
techniques
Nanoparticle Tracking
and Quantification
Techniques
Transmission Electron
Microscopy (TEM)
Scanning Electron
Microscopy (SEM)
Infrared Spectroscopy
(IRS)
Analytical Techniques
for Safety Assessment
Surface
Characterization and
Stability Analysis
Nanoparticle Tracking
Analysis (NTA)
Dynamic Light Scattering
(DLS)
High Throughput
Screening Technologies
X-Ray Photoelectron
Spectroscopy (XPS)
Differential Scanning
Calorimetry (DSC)
Cell Based Assay