Pharmaceutical Department, MET Institute of D Pharmacy, Adgoan
Neurodegenerative diseases including Alzheimer’s, Parkinson’s, and Huntington’s diseases are among the more than 1.5 billion people worldwide who suffer from abnormalities of the central nervous system. Memory loss and mobility issues are among the crippling symptoms of these illnesses, which are frequently linked to aging. The rising prevalence of neurological conditions and the dearth of potent anti-amyloidogenic treatments underscore the pressing need for novel therapeutic approaches. Derived from medicinal plants, nanoparticles (NPs) present a possible alternative due to their positive pharmacological qualities and minimal adverse effects. They can successfully cross the blood-brain barrier (BBB) thanks to their natural properties, which allows for targeted delivery to the brain and the modification of particular biochemical pathways implicated in neurodegeneration. In order to control oxidative stress, apoptosis, and neuroinflammation in ND, NPs are essential.
Alzheimer’s diseases are serious neurodegenerative conditions that impair neuronal function and cause substantial neurological damage. For the diagnosis and medicine delivery of neurodegenerative illnesses, selenium, gold, copper oxides, copper, and other nanoparticles are used. When it comes to treating neurodegenerative diseases, nanoparticles are essential. This study understands the ecologically safe methods used to produce nanoparticles, how to characterize them using various analytical techniques, and how to use them. (2)
Figure no : 1. (3)
Alzheimer’s Disease (AD) and related dementias rank as the sixth leading cause of death among the population in the United States. According to data released by the Alzheimer’s Disease Association in 2019, approximately 5.8 million individuals of all ages in America are affected by AD. A significant portion of the older population is experiencing AD and associated forms of dementia, as reported in Alzheimer’s and Dementia. AD is a chronic, progressive neurodegenerative disorder that is currently incurable and has a lengthy pre-symptomatic phase. Typically, AD is linked with cognitive challenges, behavioral issues, social difficulties, and impairments in work performance, ultimately leading to significant decline. One of the primary characteristics of AD is the abnormal buildup of β-amyloid protein (β-amyloid plaques) outside of neurons, along with the unusual accumulation of tau protein (tau tangles) within neurons. The presence of β-amyloid contributes to neuronal death by interrupting communication at synapses. While tau tangles lead to neuronal cell death by obstructing the intake of nutrients. ( 4)
Objective of herbal nanoparticles :
Role of Curcumin :
Immunofluorescence and immunohistochemical studies have demonstrated that peptide (B6)-conjugated curcumin-loaded PLGA-PEG-B6 nanoparticles reduce hippocampus Aβburden in APP/PS1 mice he BBB’s relative impermeability, which results from the close connections between cerebral microvascular endothelial cells—which are also crucial for maintaining brain homeostasis—basically prevents drugs from entering the central nervous system.
FIGURE NO 2.(6)
Because they can improve the efficiency and specificity of brain delivery, receptors with high endothelial cell expression—such as the insulin, transferrin, and integrin receptors—are particularly interesting for receptor-mediated transport (RMT) . Over the past ten years, a lot of research has focused on BBB targeting the transferrin receptor (TfR), one of these distinct receptors .*(7)
Backopa monheri
A tropical plant prevalent throughout India, Bacopa monnieri (Linn), also referred to as “Brahmi,” is a member of the Scrophulariaceae family. Steroid bacosides (A and B) and saponins are the main active ingredients in Bacopa monnieri. These active compounds enhance learning as well as memories. Other ingredients include alkaloids, flavonoids, phytosterols, and bacopa saponins F, E, and D. Glutathione reductase (GSR), superoxide SOD, CAT, and GPx are all activated by bacoside A. As a result, glutathione levels in the brain are noticeably elevated. Bacoside A inhibits lipid peroxidation via changing the function of brain enzymes such as Hsp 70 and cytochrome P450. It also improves adenosine triphosphate (ATPase) activity, preserves ionic homeostasis, and restores zinc and selenium levels in the brain.(7)
Saffron:
Crocus sativus L. flowers’ dried stigmas, or saffron, have the Ability to increase blood flow and inhibit blood stasis. Due to its pharmacological properties, which include inhibiting atherosclerosis, saffron may be utilized to prevent and cure neurodegenerative disorders (NDs).Various compounds found in saffron encompass terpenoids, anthraquinones, amino acids, and alkaloids. Among these, terpenoids are the most prevalent, with notable examples such as crocin (CR), safranal, picrocrocin, and crocetin(.8)
Ashwgandha
A complex mixture of several phytochemicals, such as alkaloids, flavonoids, steroidal lactones, steroids, salts, and molecules containing nitrogen, make up the extract of Withania somnifera (L.). Several sitoindosides, 40 withanolides, and over 12 alkaloids have been identified and isolated from the plant. withanolides are primarily responsible for the pharmacological effects. Some pharmacologically active components and metabolites of Withania somnifera (L.) and their chemical structures, Because of its remarkable pharmacological qualities, Withania somnifera (L.) is utilized as one of the main medications in Indian Systems of Medicine (ISM). The tiny woody shrub Withania somnifera (L.) is a member of the plant kingdom’s Solanaceae family. In English, it is frequently referred to as “Indian Ginseng” or “Indian Winter Cherry.” It’s known as “ashwagandha.”(9)
Ginkgo biloba
The isolated mountain valleys of Zhejiang province in eastern China are thought to be the place of origin. Dried ginkgo leaves are used to make standardized Ginkgo biloba extract (GBE), a medication used to treat dementia and memory loss, including Alzheimer’s disease.Flavonoids, including benzo-γ-pyrone derivatives, are the most active chemicals found in G. biloba leaves. This group mostly consists of biflavones (ginkgetin, isoginkgetin, bilobetin, scjadopitizuna, amentoflavone) and flavonols (kaempferol, quercetin, isorhamnetin, rutin, myricetin), as well as flavones (luteoin, apigenin) and their glycosides. Terpenoids are an important group that includes the key diterpenes: ginkgolides A, B, C, J, M, K, L, as well as the main sesquiterpene-bilobalide.N(10)
Revestol
Resveratrol, a phytoalexin chemically linked to stilbenes, is formed in significant levels in the skin of grapes, raspberries, mulberries, pistachios, and peanuts, and by at least 72 medicinal and edible plant species in response to stress conditions......( rucha)
Neuroscientists are interested in the natural phytocompound resveratrol (trans-3,5,4-trihydoxystilbene; C14H12O3) due to its neuroprotective properties. Resveratrol is an antioxidant that can prevent or delay cellular damage and illnesses caused by oxidative stress(12)
|
Component (example) |
Role of formulation |
Concentration |
|
Herbal extracts _ curcumin, ginseng, backopa monneri, gingo biloba, saffron., ashwgandha |
Active pharmaceutical ingredient |
1-30 % w/w (Depending of patency) |
|
Nanoparticles matrix (polymers) -chitosen |
Provide structural integrity and Provide stabality |
5 _-30 % w/w |
|
Stabilizers and surfactant |
Causes agglomeration and Enhance dispersion of nanoparticles |
O.5-2%w/w |
|
Binders – methylcelloulse |
Bind during compereion |
2-10%w%w |
|
Disintegration-sodium starch glycolate |
Promote breakdown for digestion |
2 -8% w/w% |
|
Lubricant -sodium starte |
Friction during compression |
0.2 -5% |
|
Fillers -microcrystaline cellulose, lactose |
Provide bulk to tablet |
50 -80% |
|
Coating agent -ethyl cellulose |
To provide the unpleasant tastes |
2-4% |
|
Colourants/ flavouring agent |
To provide texture and patients compliance |
As per need |
|
Purified water |
Solvent formulations |
As Per need |
Converting of herbal drugs into nanoparticles
Top -down method:
Methods for creating particles using top-down nanofabrication and their potential uses in medicine. Photolithography, interference lithography, electron beam lithography, mold-based lithography (nanoimprint lithography and soft lithography), nanostencil lithography, and nanosphere lithography are some of the popular top-down nanofabrication methods that we present that may be used to create nanoparticles. These include (i) targeting, (ii) drug and gene delivery, (iii) imaging, and (iv) therapy, among other current and emerging uses. Lastly, an outlook on the use of top-down methods to create nanoparticles in biomedicine is also discussed.(13)
Milling –
The disadvantages of curcumin include limited water solubility, poor absorption, rapid metabolism, rapid systemic elimination, low bioavailability, poor pharmacokinetics, low stability, and low penetration targeting effectiveness. Encasing curcumin in nanocarriers for targeted delivery is a popular technique to get around these problems. Nonetheless, the deteriorated nanocarrier products have sparked worries. We created curcumin nanoparticles and nanocurcumin without the use of nanocarriers in this study. This was accomplished by soxhlet extracting curcumin from fresh turmeric rhizome. At varying flow rates, stock solutions with varying concentrations of curcumin made in dichloromethane were added to boiling water and sonicated for varying lengths of time. At 0.10 mL/min flow rate, 30 min sonication time, and a concentration of 5.00 mg/mL stock solution, an average particle size of 82 ± 04 nm was achieved(14).
Bottom up
In the current work, a straightforward nano-precipitation technique was used to create cationic nanoparticles of curcumin, chitosan, and poly(~?-caprolactone). An almost spherical form was displayed by the produced curcumin-loaded chitosan/poly(?-caprolactone) (chitosan/PCL) nanoparticle. Its diameter varied between 220 nm and 360 nm, and its zeta potential varied between +30 mV and 0 mV in relation to pH value. Fluorescence spectrum analysis was used to confirm that curcumin had been encapsulated into nanoparticles. Over the course of five days, an in vitro release investigation demonstrated the sustained release behavior of curcumin from nanoparticles.(15)
Main procedures for Obtained nanoparticles Formulation
|
Method |
Procedure |
Advantages |
Disadvantages |
Size range (nm) |
Encapsulation efficacy |
Release Efficacy |
|
Co Servation |
Desolution of a polymer in organic Solvent Suspension of a Curcumin studying and mixing centrifugation |
Inexpensive Absence of haz solution Hazardous Solution |
Requires a large amount of solvent |
87-600 |
45 |
90 after 10 days |
|
Nnano P. Precipitation |
Dilution of a polymers in all the Solvent suspension of a coal command staring mixing in water |
Facility to develop Nana, practical in a one step. Not much expense involved in a low electric power is required |
They success of a preparing Nanoparticle a restricted only a narrow region of the polymer/ solvent/ antiseptic composition map |
125 -500 |
90 |
|
|
Spary Drying method |
Curcumin and polymers are they sold in the same mixture of a Solvent dissolved offer solvent by a hot air flow |
Rapid continuous cost effect to REPRODUCIBLE single step and thus scalable process |
Low yelid |
125 -70 |
90 |
|
|
Solvent Evaporation Method |
A evaporation solvent used curcumin steering surfactant and adding curcumin along oil and water |
Prevention of thermal deposition by using low temperature in Evaporation Step |
Expensive use of reagents time consuming evaporation process |
90-120 |
80 |
|
|
Micro Emulsion |
Sterling a Suspension and adding of curcu I oil and water |
Very High Increase of Curcumin Biological |
Very Sensatiable to temperature in the Ph variation during synthesis |
2-100 |
80 |
|
|
N. Emulsion P. Polymer Sation Method |
surfactant a dissolve in pure water. By the Ultrasonic Curcumin dissolved in the organic amount added to surfactant |
Fast and Radially scalable method |
Not reported |
85-200 |
70 |
|
(16)
|
Ingredient |
Amounts |
|
Curcumin |
45 |
|
Revestol |
45 |
|
Gingo Biloba |
45 |
|
Backopa Monheri |
45 |
|
Ashwgandha |
45 |
|
Saffron |
45 |
|
Microcrystaline Cellulose |
90 |
|
Lactose |
30 |
|
Starch |
30 |
|
Magnesium Stetarte |
4,5 |
|
HPMC |
4.5 |
|
Sodium Lauryl Sulphate |
1.5 |
E.g. this quantity taking 450 mg
Curcumin weight = Curcumin contents × 100
Total tablet weight
Where, Curcumin content = 45 mg (the actual AMOUNT of curcumin in tablet)
Total tablet weight =450 mg ( total weight of tablet)
So, the calculate the percentage of curcumin the Tablet:
Curcumin percentage:45Mg ×100
450mg
Curcumin Percentage =10%
This mean 10% of the tablet total weight is a Curcumin
Tablet manufacturing:
Dry mixing method
It is necessary to see a mixer’s operation as creating a balance between mixing and segregation. It is suggested that mixers be categorized as either segregating or non-segregating after discussing the mechanisms underlying these operations. Similar classifications of the components to be combined can be used to determine which mixer is best for a given task: materials that have a tendency to separate should not be placed in a “segregating mixer.” Lastly, the necessity of treating a mixture carefully to avoid(17
Granulation technique
One of the most important unit activities in the manufacturing of pharmaceutical dosage forms, primarily tablets and capsules, is granulation, which is the process of particle enlargement by agglomeration technology. Fine powders are converted into easily compressible, dust-free, free-flowing granules through the granulation process. However, granulation presents many difficulties because the resulting granules must meet strict quality standards for content homogeneity and physicochemical characteristics like granule size, bulk density, porosity, hardness, moisture, compressibility, etc., in addition to the drug’s physical and chemical stability(18).
Figure no :3(19)
Compression:
Compaction work, elasticity/plasticity, and time-dependent deformation behavior of pharmaceuticals are described by mathematical models, force-time, force-distance, and die-wall force parameters of tableting. Compaction-related issues can be predicted using a variety of tableting performance metrics, including the bonding index, brittle fracture index, and strain index. The physico-technical characteristics of popular tableting excipients related to compaction have been studied, with a focus on choosing the best combination to reduce tableting issues. To increase their functionality, specialized technologies like coprocessing API and excipients might be employed.(20
Coating:
shielding a component or building from harm caused by chemicals or mechanical forces. Because no new parts need to be fabricated, this protective feature has the advantage of lowering manufacturing costs. Hard and stiff metallic alloys, ceramics, bio-glasses, polymers, and tailored plastic materials are among the coating materials that are available, providing designers with a wide range of options for long-lasting protection. Many techniques have been presented and studied thus far, including sol-gel, thermal spraying, micro-arc oxidation, physical/chemical vapor deposition, and electrodeposition. Despite the benefits of each of these procedures, their use is always constrained by disadvantages. However, there are numerous ways to use the advantages of each process in a multi-method coating to overcome the shortcomings of coating processes. These coating techniques are grouped and contrasted in this article.(21)
Pre formulations study of a Granules
Angle of repose:
The angle of repose was evaluated using the fixed funnel technique. A 5 g sample of the powder mixture was introduced into a glass funnel. The bottom tip of the glass funnel was positioned 5 cm above the ground. The height (h) and radius (r) of the resulting pile were measured and then calculated as follows:
θ = tan−1h/r
TAPPED DENSITY
The tapped density of the powder was measured by filling a weighed 100 ml graduated cylinder (with a diameter of 30 mm) with powder until it reached about the 70 ml level. The graduated cylinder was then tapped until a stable volume was reached, and the final volume of the powder bed was noted. This typically happens after about 500 taps. (23)
Disintegration test
Orally disintegrating tablets (ODT) are solid dose forms that quickly dissolve when in contact with saliva in the oral cavity. Among the several characterisation methods, disintegration time is one of the most important features to ensure that the ODT disintegrates within the recommended US Food and Drug Administration (FDA) time of 30 seconds or the European Pharmacopoeia period of 3 minutes1. The current approved ODT disintegration test is the United States Pharmacopeia (USP) standard test method for immediate release solid oral dosage forms, as depicted in Fig. 1. This method uses a basket rack connected to a rod that oscillates vertically within a beaker filled with roughly 800 ml of disintegration media.(24)
Friabality test
Studies were conducted to determine what changes happened in the physical qualities of compressed tablets as the operation of a rotary tableting machine was altered. Thin large-diameter tablets exhibited a capping propensity that was not seen in smaller or thicker tablets. Tablets held at 71% relative humidity for 28 days retained their crushing strength, however they became more friable. Increasing compressional speed decreased crushing strength and increased capping tendency, but had no effect on compressed tablet friability. The tablets responded more elastically at higher compressional rates than at lower speeds. The physical qualities of the compressed tablets remained unchanged when the tablets were compressed at different depths in the die.(25)
The purpose of the United States Pharmacopeia (USP), European Pharmacopeia (Pharm. Eur.), and Japanese Pharmacopeia (JP) harmonized monograph on tablet friability test is to evaluate the mechanical strength of a batch of tablets(26)
CONCLUSION:
Several studies have shown evidence for the neuroprotective potential of natural products and natural bioactive substances against neurodegenerative disorders. Numerous neurodegenerative illnesses must be prevented and treated using natural products and their significant bioactive substances to avoid negative side effects. Given the complex nature of the pathological process of neurodegeneration, several mechanisms of action are crucial for developing neuroprotective techniques for the treatment and prevention of neurodegenerative illnesses. It is preferable to use natural products and their bioactive components, which have diverse modes of action and display neuroprotective effects. (27).Furthermore, a key component of natural products’ neuroprotective effects and their bioactive constituents is their capacity to pass the blood-brain barrier. As a result, the creation of fresh methods and techniques, including using (28)
REFERENCES
Vrushali Ghuge, Srushti Dhumane, Latesh Patil, M. R. N Shaikh, Green Synthesis using Nanoparticles using Herbal Plants as an Eco-Friendly and Therapeutic Potential Approach for Alzheimer’s Disease, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 1378-1388. https://doi.org/10.5281/zenodo.17571750
10.5281/zenodo.17571750
