INTRODUCTION:

Cancer has been a continue ground battle all over the world with many advancements in preventive therapy. The disease is characterised by continue multiplying of cell in the human body and unable to stopped or controlled¹.

From various cancer, lung and breast type cancers are the leading cause of death in men and women respectively^2,3. In 2012 the commonly diagnosed cancer was lung cancer (approx. 2 million) and breast cancer (1.77 million)⁴. Lung cancer was responsible for approximately 17% of total new cancer cases and 25% of cancer deaths in men whereas breast cancer calculated for 24% of all cancer cases and 16% of all cancer deaths among women^2,5. There are number of chemotherapeutic drugs which are used for the treatment of cancer. But these drugs have their limitations due to their various toxic side effects on nontargeted tissues causing severe health issues. Anticancer drugs must kill cancer cells with no disturbing normal cells than it will be known as successful anticancer drug. Present treatment such as radiotherapy, chemotherapy and drugs derived by chemically. The treatment carried out such as chemotherapy may do patient a lot of pains, and damage their health system, and because of this a focus is put on using other alternative treatment against cancer⁶. For Thousands of years herbal medicine has been used and in developing countries it is used as main sources for medical treatment. The research has profound into investigation of plant as herbal extract for the preparation of potential nanomaterial-based drugs for such a disease like cancer⁷. Development in the field of medical science is raised by the progress of nanotechnology which provides numerous solutions to deal with dangerous and harmful diseases. The nanotechnology is a significant and has many applications in various sectors like electrics⁸, clothing materials⁹ and very important in medical care as treatment, diagnosis, and delivery of drug at targeted site for the well-being of human¹⁰. Currently nanoparticles are an excellent platform because of its biological applications. Nanotechnology possesses an innovative and makes a possible platform which guaranteed to offer a wide area of original utilization and developed procedures to biological and biomedical functions. The challenge in the cancer treatment is to avert the non-cancerous cell from demolition while damage and target tumour cell. The nanoparticle-based drug carries can solve many problems such as drug solubility, drug bioavailability¹¹. Nanoparticle formulations are extraordinary blessing for the treatment of disease such as cancer.

Nanoparticles: Types

Silver:

Silver nanoparticles are scientifically proven to be most efficacious because they possess good antimicrobial property against bacteria, viruses and othermicroorganisms^12,13. Silver nanomaterial’s are broadly used as antimicrobial agents, for sunscreen lotions and in textile industries etc.^14,15 The plants i.e. Azadirachtaindica¹⁷ Capsicum annuum¹⁶, and Carica papaya¹⁸Nanoparticles are more site targeted treatment for hard to manage disease such as cancer disease, the biosynthesis of silver nanoparticles have been successful reported.

Gold:

For protein interactions identification in immunochemical studies gold nanoparticles (AuNPs) are used. They are used as lab tracer in DNA fingerprinting to detect existence of DNA in a sample. Aminoglycoside antibiotics i.e. streptomycin, gentamycin and neomycin are also detected by using these nanoparticles. Diagnosis of cancer, detection of cancer stem cells, and identification of different classes of bacteria done by using Gold nano rods^19,20.

Magnetic:

Magnetic nanoparticles are known to be biocompatible. For magnetic resonance imaging (MRI), targeted cancer treatment (magnetic hyperthermia), guided drug delivery, gene therapy, stem cell sorting and manipulation and for DNA analysis they have been actively considered²¹.

Alloy:

Alloy nanoparticles exhibit structural properties that are different from their bulk samples. Since Ag has the highest electrical conductivity among metal fillers and, unlike many other metals, their oxides have relatively better conductivity, Ag flakes are most widely used. Bimetallic alloy nanoparticles properties are influenced by both metals and show more advantages over ordinary metallic NPs⁷⁰.

LITERATURE REVIEW:

KUO (2004, E. P. 2006, 2006) summarized the preparation of water-miscible extract from plant solanum genus consist of 60-90% solasonine and solamargine. This extract consists of nanoparticle size, less than 1 μm, that can be dissolved in water directly to produce clear aqueous solution of solubility range of 2 ~ 20 mg/ml or higher. The extract is used in pharmaceutical formulation, to decrease or inhibit the growth of cancer cells, in lungs and liver cancer^22-24.

Gorur Amita et al., (2007) processed agar bionanoparticles ranging from 50 nm - 80 nm. The bio nanoparticles used to avert calcium- induced clotting of blood plasma of human and to treat/inhibit the human epidermoid carcinoma HEp2 cells²⁵.

Sambandam et al., (2007) proposed the oligosaccharide bionanoparticles preparation from the Moringa oleifera Lam gum, particle size between 60nm- 100 nm. This protects DNA and RNA plasmid from degradation, with the inhibition of growth of onion roots, which leads to death of human epidermoid carcinoma HEp2 cells²⁶.

Danek, (2013), explained the combination therapy for cancer treatment by the administration of vincristine, vinblastine as chemotherapeutic agents, in an effective amount and extract of cyanobacteria in the nanoparticle form by orally, subcutaneously, intravenously²⁷.

Einbond et al., (2013), describes a nanoparticle effective dose of triterpene complex nanoparticles or triterpene glycoside nanoparticles which are complex compounds liposome-encapsulated uses to prevent cancer and act as chemotherapy agents for breast cancer²⁸.

Patel Ashok, (2012) describes nanoparticle containing hydrophobic compounds of phenol like curcuminoids and polymethoxylated flavones in addition with hydrophobic polymer like secalin, zein or of this combination polymer. This composition increases water dispersibility, stability against sedimentation and increase bioavailability. These are used as anticancer and antioxidant agents²⁹.

Ringas et al., (2011) describes a method to treat various cancer such as lung, colonic, breast by administration of phosphor- ibuprofen, phospho-valproic acid or pharmaceutical salts together in combination of cimetidine and curcumin as bioavailability enhancer, this bioavailability enhancer is in lipid nanoparticles form. This method is used to treat cancer by periodically administration of pharmaceutical salts³⁰.

Yang et al. developed Cuscuta chinensis nanoparticles by nanosuspension method to improve absorption of which poorly water-soluble constituent, quercetin³¹. Similarly, Zhang and Kosaraju studied a biopolymeric drug delivery system for controlled release of catechin. The antioxidant activity of catechin is decreased dramatically when it is introduced in an alkaline environment³². To protect catechin, chitosan encapsulated catechin particles were developed. Also, Bhatia et al. developed chitosan nanoparticles for the extract of Ziziphus mauritiana and checked the effect on its immunomodulatory activity³³ Nano particles of size ranging from 10 to 1000 nm. Nanoparticles have several advantages including bioavailability enhancement, solubility enhancement, and efficacy enhancement.

Mei et al. studied the anti-inflammatory activity and transdermal delivery capacity³⁴ prepared from triptolide incorporated solid lipid nanoparticles. The formulation consisted of 5% tristearin glyceride, 1.2% soybean lecithin and 3.6% polyethylene glycol monostearate. In other study, Mei et al. tried to reduce the hepatotoxicity produce by triptolide and improved its anti-inflammatory activity by formulating triptolide-incorporated solid lipid nanoparticles³⁵.

Ali et al. developed a novel micro emulsion³⁶. Chen et al. studied microemulsion systems for transdermal delivery. Microemulsion preparations are further based gel formulation of babchi oil (Psoraleacoryfolia)³⁷. Similarly, Wang et al. made an attempt to enhance antiinflammatory activity of curcumin by formulating it into nanoemulsion Yan-yu et al. conducted a study on oral bioavailability of silymarin encapsulated into proliposome. Silymarin proliposomes had > 90% encapsulation efficiency with particle size of 196.4 nm. The study indicated improved bioavailability of silymarin in proliposome form as compared with pure silymarin³⁸.

Sou et al. developed and conducted a modified nano-lipid vehicle loaded with curcumin to deliver it into tissue macrophages through intravenous injection. Curcumin was encapsulated into a phospholipid vehicle comprising 1,2-dimyristoyl-sn-glycero-3-phosphocholine; 1,5- dihexadecyl ester; 1,2-distearoy sn-glycero-3-phosphoethanolamine-N-[monomethoxy poly(ethylene glycol) (5000)] in a molar ratio of 10:1:0.06³⁹. Fang et al. studied liposomal formulation encapsulating tea catechins. Permeation studies showed appreciable permeation of (+)-catechin when encapsulated in liposomes formulated with anionic surfactant deoxycholic acid and dicetyl phosphate in the presence of 15% ethanol⁴⁰.

Kurzrock et al., (2011), studied the use of liposomal curcumin in the prevention/treatment of pancreatic cancer, melanoma, and breast cancer in human patients or other mammalians. It has been seen to restrain the growth of cancer in the laboratory and has prevented the appearance of cancer in animals, when used as a liposomal drug delivery, in the form of nanoparticles or nanocapsules, given parenterally. Described a method to inhibit the growth of cancer, by exposing the cells in-vitro to the formulation of a liposomal drug delivery system containing encapsulated curcumin. The ratio of curcumin to the lipid combination (w/w) stated has been 1:75 to 1:10. It has been revealed that liposomal curcumin demonstrated a more significant effect on cancer than plain curcumin⁴¹.

Sanjeeb Kumar Sahoo, (2011), described a water-soluble, curcumin-loaded nanoparticle system for cancer therapy consisting of glyceryl monooleate (GMO), polyvinyl alcohol (PVA), and pluronic F-127, with a uniform particle size of less than 200 nm, having a high surface charge and high zeta potential, around - 32 mV, which enhances the solubility, stability, and bioavailability of the entrapped curcumin used for cancer therapy. The curcumin-loaded nanoparticle system is prepared by incorporating curcumin into a fluid phase of GMO, and then subjecting this mixture for emulsification with PVA and a pluronic F-127 solution. Next, the final emulsion is lyophilized with a freeze dryer, to produce lyophilized powder. It has been investigated that curcumin shows its anti-proliferative activity against cancer cell by inducing apoptosis⁴².

Frautschy et al., (2007, 2009), described solid lipid nanoparticles and the microemulsion of the curcuminoid, micellar form of curcumin and its derivatives. The carrier comprises of lipid micelles of phosphatidyl choline and microcapsulated oils. The antioxidant contains ascorbic acid and a glucuronidation inhibitor consisting of tetrahydrocurcumin, which is relatively stable in water at a physiological pH and helps to enhance absorption and the plasma level of curcumin for treating Alzheimer’s disease and other age-related disorders. The present invention enhances the bioavailability of curcuminoid. The composition is suitable for administration to humans or mammals topically, enterally, parenterally or by some other mode of administration^43,44.

Desai, (2010), has provided a curcumin cyclodextrin combination in the form of a microemulsion, solid lipid nanoparticles, solid powder, liquid, and a microencapsulated oil or gel, and this combination is used for the prevention and treatment of various diseases like Alzheimer’s disease, asthma, rheumatoid arthritis, oncological diseases, and so on, because, curcumin has anti-inflammatory and anti-angiogenic properties. As curcumin is very poorly absorbed and has very low bioavailability, the patent has described a method to increase the delivery of curcumin by complexation with cyclodextrin, which has the capability to increase the bioavailability⁴⁴. DI Mauro, (2013), has disclosed methylated curcumin-methoxy stilbene hybrid molecules, particularly used in treating cancer. Curcumin does not penetrate easily through the human digestive tract and is subject to intestine-based metabolism and rejection and less than 1% of oral curcumin enters the plasma. The small amount of curcumin that enters the bloodstream is rapidly metabolized by the kidney and liver. Although curcumin is highly lipophilic (and easily crosses the blood-brain barrier), only very small amounts of orally administered curcumin are registered in the serum and in the brain tissue. It has been reported that high oral doses of curcumin cause problems such as rash and diarrhea, and headaches likely produced by metabolites of curcumin. They describe intranasal administration of a formulation comprising of an effective amount of curcumin to the olfactory mucosa across the cribriform plate and into the brain, to treat a neurodegenerative disease such as Alzheimer’s disease⁴⁵.

Baktha et al., (2003, 2004), proposed capsaicin, a pungent substance derived from the solanacae family, for topical treatment in nanoparticle, microemulsion or nanocapsule form to treat/modulate specific receptor activity in vivo or in vitro to treat chronic or acute pain, including neuropathic pain^46,47.

Kanazawa, (2009), described a formulation, which includes a nanoparticle comprising of 0.1% to 100% w/w of a blood circulation promoter such as tocopherol-derivative, a nicotinic acid derivative (Niacin, vitamin B3), Swertia japonica extract (Makino), Sunflower, Tocopherols (vitamin-E), olive oil (Tocotrienols), palm oil, and a biodegradable polymer-like protein, such as, collagen, gelatin, albumin, casein, acid treated gelatin, ovalbumin, sodium casein, and so on. An, β, γ, and κ casein, which is a milk-derived or bean-derived protein, is also used alone or in combination. The protein is then subjected to a cross-linking treatment after the formation of a nanoparticle by using transglutaminase obtained from guinea pig liver, goat, rabbit, or human liver, and treated with organic solvents like ethanol, acetone, and isopropanol. This composition can be used as a transdermal absorbable agent, topical therapeutic agent, oral therapeutic agent, intradermal parenteral injection, subcutaneous parenteral injection, cosmetic, functional food, supplement or a quasi-drug⁴⁸.

Chaudhary et al., (2011), described a novel herbal nano-emulsion containing lemon juice and er in 1:1 ratio or lemon alone as a pharmaceutically active aqueous layer/phase entrapped in essential oils like Tea tree oil (18 ± 5%), Rosemary oil (2 ± 5%), Tulsi oil (4 ± 5%), Lavender oil (5 ± 5%), and Mentha oil (7 ± 5%), used as an oil phase. The present nano-emulsion has been claimed for prophylactic and therapeutic topical treatment of acne and other skin disorders like eczema, psoriasis, aging, and scarring, with increased efficacy, improved percutaneous penetration, and excellent thermodynamic stability, with low skin irritation and long shelf life and reservoir effect, which promotes drug localization in the skin that enables controlled delivery of active or therapeutic agents⁴⁹.

Leighlon et al., (2013), invented a method to treat a subject suffering from herpes simplex virus-induced inflammation by the topical application of a composition containing an effective amount of anti-histamine, with the base composition containing essential extracts of lemon balm (Melissa officinalis), calendula flowers (Calendula officinalis), green tea gunpowder (Camellia seninsis), and green rooibos (Aspalatus linearis) in the form of emulsion, nanoparticles, suspensions, patches, and the like^50,51.

Parkinson’s disease (PD) is a progressive degenerative disorder of the central nervous system, characterized by rigidity, tremor, and hypokinesia. PD results primarily from the death of the dopaminergic neurons in the substantia nigra, a region of the midbrain^52,53. As PD is associated with dopamine deficiency, drugs affecting the brain dopaminergic system like Levodopa (Dopamine precursor), Carbidopa and Benserazide (decarboxylase inhibitors) have been shown to be beneficial⁵⁴.

Nelson, (2002, 2009), described a composition to increase cellular respiration of melanized catecholamine neurons and invented a method to alleviate or stop the appearance and progress of Parkinsonism disease symptoms. The composition contains (-) chloroquine, which is adsorbed on suitable carriers like nanoparticles to cross the blood-brain barrier^55,56.

Fig. 1: Herbal Nanoparticles target Cancer Cells

Solubility, Bioavilability, and Stability Enhancement:

Chaniyilparampu et al., (2010, 2012) prepared an ophthalmic and nasal formulation of curcuminoid and its metabolites. The nasal nanoemulsified formulation is used in animals or humans in an ocular or nasal diseased condition. They prepared nanoemulsified curcumin with pharmaceutically acceptable surfactants, namely, polysorbate 80 and 20, poloxamers, octoxynol, and the like, which were effective in increasing the bioavailability of the active compound, curcumin. These were used to treat several allergic and inflammatory diseases in humans and animals in the form of nasal sprays and ophthalmic gels or aqueous ophthalmic eye drops. The diseases to be treated or prevented were several inflammatory diseases of eye and nose, like allergic conjunctivitis or allergic rhinitis characterized by itching, redness, and edema of the eye, due to histamine release^57,58.

Khar et al., (2011), described a method to enhance the bioavailability of curcumin by preparing their nanoparticles with sizes from 50 nm to 284 nm by using chitosan, which binds curcumin and enhances its bioavailability 10-fold. The present patent has disclosed a method of coating the chitosan nanoparticles by curcumin, which includes dissolving the curcumin in alcohol, and spraying this solution stored at 25 - 40°C, under high pressure and nitrogen atmosphere, into an aqueous solution with a low percentage of organic acid, which is stirred continuously at room temperature⁵⁹.

Nair et al., (2011), proposed a process for the nanoemulsification of curcumin with pharmaceutically acceptable nonionic surfactants like polysorbate 80, polysorbate 20, poloxamers, octoxynol, and a non-ionic co-solvent like PEG 400 and PEG 6000. The process employs sonar energy, which enhances the aqueous solubility of the curcumin, because it is a highly lipophilic compound. The main objective of the present study was to enhance the aqueous solubility of curcumin⁶⁰.

Xu et al., (2011), disclosed a silymarin nanoparticle formulation, which is highly efficient and long-acting, thus, given only once in three days. The bioavailability of silymarin is low due to its poor water solubility; hence, this invention focuses on increasing its oral bioavailability. Silymarin is useful for liver protection, blood lipid reduction, prevention of diabetes, and protection of myocardial and anti-platelet aggregation. The present formulation is in the form of loaded nanoparticles, which enable silymarin to function for a long time, continuously, in slow-release mode, with a triple release mechanism comprising of a quick release of solid dispersion, regular release of a hydrophilic gel matrix, and a long-acting slow release of the ordered mesoporous material. It is prepared by combining the techniques of solid dispersion, ordered mesoporous nanoparticle, and hydrophilic gel matrix, and it is then converted into granules. The drug loading rate of a silymarin loaded silica nanoparticle is 51.95 to 52.87%. This nanoparticle technique enhances the speed and extent of physical absorption of silymarin. Using those slow-release granules, the silymarin formulation can be prepared in the form of a tablet or capsule, which enhances the bioavailability of silymarin⁶¹.

Jacob, (2012), disclosed a composition in the form of nanoparticles or encapsulated in liposomes, to enhance the bioavailability of curcumin, which consists of the curcumin plant extract, vanilla, and ginger, which are rich in gingerol and vanillin, or capsaicin can also be used in this composition along with ginger and vanilla⁶².

Payne et al., (2013), described a method that consists of curcumin dissolved in an aqueous solution like water, alcohol and the like, at an enhanced concentration, which increases the stability by reducing the precipitation and degradation of the solution. This composition, that is, the curcumin nanoparticles are used for an antioxidant, anti-inflammatory, antiviral, antibacterial and antifungal effect⁶³.

Tengler et al., (2013), described a composition and methods to control the release of active agents in a shelf-stable liquid formulation containing a herbal extract like oregano leaf extract, prepared by blending one or more controlled-release microbeads or nanoparticles containing one or more active agents, which are used to prepare a dense thixotropic solution, with a density of one or more microbeads, thixotropic agent, water or a preservative. These are used to reduce bubble formation, and then the nanoparticles are mixed with that thixotropic solution in a mixer without scraping paddles⁶⁴.

Wertz et al., (2008), described a nanoparticulate composition containing a poorly soluble active agent from a group consisting of a drug, vitamin, herb, cosmetic agent, hair cosmetic agent, hair dye, and lysozyme as a surface stabilizer. In this they have claimed a bioadhesive nanoparticulate composition containing a lysozyme, having an average particle size of less than about 200 nm⁶⁵.

Hu et al., (2011), have proposed that nanoparticles of curcumin can be produced with a high repetition rate ultrafast pulsed laser ablation in liquids, which is a highly efficient method and has higher production rates, producing an organic nanoparticle colloidal suspension with particles of 100 nm, stable at 25°C for at least one week in the absence of any stabilizing agents. Through proper control of laser parameters like pulse repetition rate, pulse duration, pulse energy, and movement of the laser beam over stable nanoparticles, a colloidal suspension can be produced⁶⁶.

Table 1: Various Nanoparticle Herbal Drugs Formulation:

Plant name	Family	Active ingredient	Biological activity	Formulation	Reference
Tussilagofarfara	Asteraceae	Sesquiterpenoid	Anticancer activity	silver and gold nanoparticles	33
Perillafrutescens	Lamiaceae	Triterpenoids, flavonoids, and polyphenols.	Anticancer activity	Silver Nanoparticles	34
Curcuma longa	Zingiberaceae	Curcuminoids	Anticancer activity	Curcuminoids solid lipid nanoparticles	35
Taxusbrevifolia	Taxaceae	paclitaxel	Anticancer activity	paclitaxel-loaded nanoparticles	36
Berberis vulgaris	Berberidaceae	Berberine	Anticancer activity	Berberine-loaded nanoparticles	37
Artimisiaannua	Asteraceae	Artemisinin	Anticancer activity	Artemisinin nanocapsules	38
Camtothecaacuminata	Nyssaceae	Camptothecin	Anticancer activity	Camptothecin encapsulated nanoparticles	39
Cuscutachinensis	Convolvulaceae	Quercetin	Anticancer activity	Quercetin-loaded nanoparticles	40, 41
Camellia sinensis.	Theaceae	epigallocatechin	Anticancer activity	gold nanoparticle	42,43
Hypericumperforatum	Hypericaceae	Hypericin	Anticancer activity	Hypericin-loaded nanoparticles	44
Podophyllumpeltatum	Berberidaceae	podophyllotoxin	Anticancer activity	Podophyllum loaded nanoparticle	45,46
Catharanthusroseus	Apocynaceae	vincristine	Anticancer activity	Vincristine-loaded hydroxyapatite nanoparticles	47

Conventional Use of Herbal based Nanoparticles:

Fig. 3: Conventional use of herbal Based Nanoparticles

CONCLUSION:

Recently herbal drugs are getting more valuable and knee area for interest because of their disease treatment with minimal or no side effects. Besides this herbal drugs have poor bioavailability, poor solubility and instability and minimal use. To overcome such limitations and problems nanoparticles plays a major role, not only to increase solubility, increase bioavailability but also act as targeted drug delivery at cancerous cell. Hence different nanoparticles of herbal drugs have been carried out for better therapy and to prevent from physiochemical degradation.

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Received on 23.06.2023 Modified on 15.12.2023

Res. J. Pharma. Dosage Forms and Tech.2024; 16(2):194-202.

DOI: 10.52711/0975-4377.2024.00031