INTRODUCTION:

Nanotechnology is one of the most popular, trending and attractive technique which has highly drawn the attention of many scientists and researchers nowadays. It simply involves exploitation of a substance on an atomic, molecular and supramolecular scale [1]. According to National Nanotechnology Initiative, nanotechnology is the technique to manipulate matter with at least one dimension sized from 1–100 nm [2]. Nanotechnology mainly includes studies or development of material having unique properties that originates from their nanoscale dimensions. This technology has shown rapid progress in developing materials in the field of pharmaceutical science such as developing nanomedicine, tissue engineering, targeted drug delivery, biosensors etc [3].

Apart from this there is large number of medicinal plants having a wide variety of usefulness and effectiveness against large number of diseases therefore; green synthesized nanoparticles from these medicinal plants have become an enthusiastic interest for researchers to carry their interest of work [4]. Hydroxyapatite is a naturally occurring mineral apatite with chemical formula Ca₁₀(PO4)₆(OH)₂ . It constitutes up to 50% by volume and 70% by weight of human bone, generally referred to as “bone mineral” [5]. Also it constitutes 70-80% of mass of dentin and enamel in teeth [6]. Hydroxyapatite is a calcium phosphate compound which is thermodynamically stable in all terms of physiological conditions such as pH, temperature, pressure and composition of body fluids [7]. There are multiple physiological system which works together to maintain homeostasis in a human body. In this article we summarize the present knowledge based on the effects of nanostructure of hydroxyapatite and its applications in the pharmaceutical field. Moreover there are also platform for the study of toxicity of nanoparticles which is referred to as “nanotoxicological study” [8].

Figure 1: Pharmaceutical application of HA [9]

Due to its similarity in chemical and physical property to human hard tissue, hydroxyapatite is widely used in biomedical application in various forms. The very recent and latest technology make use of the nanostructure of hydroxyapatite due to its outstanding marked property such as – Biocompatibility, Bioactivity, Nontoxicity, Non inflammatory, Osteoconductivity etc [10].

This Nano hydroxyapatite has vast applications in biomedical fields such as [10, 11] –

· In bone fillers and bone supplements it plays an integral role.

· Used to ease osteointegration.

· Used widely in the field of bone tissue engineering.

· Used in toothpastes as remineralizing agent.

· Used in early carious lesions treatment.

· Also used in the spine, dental, maxillofacial surgery.

· Drug and gene delivery and many more.

NANOSTRUCTURE OF HYDROXYAPATITE:

"Apatite" generally is a word which is derived from Greek word "apatein" which means "to deceive". The group of compounds having a general formula M₁₀(XO₄)₆Z₂, comes under the category of "apatite" where M²⁺ is metal species and XO4^3- and Z^- are anions. The nomenclature of every apatite molecule depends upon the type of groups attached to it. For example; hydroxyl apatite (M is calcium, X is phosphorus and Z is the hydroxyl radical), similarly chlorapatite (where Z is chlorine) and fluorapatite (where Z is fluorine). Atomic ratio of hydroxyapatite Ca/P is 1.67 having chemical formula Ca₁₀ (PO₄)₆(OH)₂. The compound hydroxyapatite accounts 39% by weight of Ca, 18.5% of P and 3.38% of OH. With some exception in a monoclinic system, hydroxyapatite always undergoes crystallization in a hexagonal system [12,13]. The system belongs to the hexagonal space group P63/m, with hexagonal rotational symmetry and a reflection plane and with cell parameters of a=b=9.418 Å y c=6.884 Å. Figure 1: shows structure of hydroxyapatite.

The structure of hydroxyapatite shown below constitutes mainly of phosphate ions (PO₄^3-) which are arranged in a tetrahedral manner and considered as the building block of the structure. There are 2 oxygen atoms which are arranged along the c axis and rest 2 oxygen is present horizontally in a unit structure of HA. Phosphates are differentiated into 2 layers in the unique structure of HA, having ¼ and ¾ of height respectively, which in turn leads to the formation of 2 types of channels along the c axis i.e. symbolized by A and B.

The walls of channels A type are occupied by oxygen atoms of phosphate group and calcium ions, called calcium ions type II [Ca (II)], consisting of two equilateral triangles rotated 60 degrees relative to each other, at the heights of 1/4 and 3/4, respectively. Type B channels are occupied by other ions of calcium, called calcium ions type I [Ca (I)]. In each cell there are two such channels, each of which contains two calcium ions at heights 0 and 1/2. But in the structure of HA channel A type are replaced by OH ions.

The hydroxyapatite developed biologically are much more complicated because they are not stoichiometric, have an atomic ratio Ca/P <1.67 and does not contain only ions and radicals of the HA but also traces of CO3, Mg, Na, F and Cl. It is important to note the Ca/P value and degree of crystallinity in the structure of HA. The closer the value of Ca/P to 1.67, the greater is the stability of the material inside the human body, whereas if this Ca/P value decreases, bioactivity should be greater. To develop particles or substance made up of HA conditions such as type of techniques used, environment condition etc should be well maintained.

Figure 2: Representation of structure of hydroxyapatite.

SYNTHESIS OF NANOHYDROXYAPATITE (nHA):

Nanoparticles have wide-range of applications in the field of pharmaceutical sciences. Henceforth, the build out of synthesis procedures for nanoparticles is a steadily evolving branch of nanotechnology. Therefore, the very first attempt of every researcher is the modification of various properties of nanoparticles such as- bioactivity, morphology and particle size, as a result of which large number of techniques to synthesize nanohydroxyapatite has been developed.

Mainly two approaches have been considered for the nanohydroxyapatite synthesis one is top down approach i.e. consecutive breakdown of a substance to produce desired nanoparticles and the other one is bottom up approach i.e. generation of desired nanoparticles by constructing a substance starting from its atomic level. Till date mostly bottom up approach have been reported for the nanohydroxyapatite synthesis [14].

Various techniques for the synthesis of nanohydroxyapatite are discussed as follows-

Chemical precipitation method:

The synthesis of nanohydroxyapatite by chemical precipitation method is one of the most versatile, economically advantageous and popular method. It was reported that nanohydroxyapatite synthesized through this method was mostly agglomerated, and these agglomerated particles were referred to as clusters of ultrafine primary particles as per the Rahaman’s classification [15]. Advantages of this method are – ease of production of nanohydroxyapatite particles and effective control of particle sizes especially when designed for prolong time in systemic circulation [16]. In summary, the chemical precipitation method to synthesize the nanohydroxyapatite particle is the most simplest, reliable and economical method.

Generally the synthesis of nanohydroxyapatite particles by chemical precipitation method involves steps where from the aqueous solution of calcium nitrate tetrahydrate (Ca (NO₃)₂.4H₂O) and ammonium dihydrogen orthophosphate (NH₄H₂PO4) calcium phosphate is precipitated. After ageing for 24hr, the precipitate was washed in distilled water, freeze-dried and calcined at 300 °C. Ball mill is used to separate the calcined precipitate and screened to obtain particles having size below 50 nm [17, 18]. Precipitation was carried out at a pH of 11 at 0°c for 2 hr.

· Tas et al., [19] reported the synthesis of nanoparticles using chemical precipitation method which involved modified simulated body fluid (SBF) solutions; calcium nitrate tetrahydrate and diammonium hydrogen salts were dissolved into it.

Hydrothermal Synthesis method:

Hydrothermal method is the method which involves the chemical reaction where the substances is heated in a packaged environment above the normal temperature and pressure and synthesis of closely-grained, pure identical crystals with required morphological features and narrow size distribution is mainly included in this method [20,21]. This method overcomes the disadvantages of chemical precipitation such as – irregular shape of nanohydroxyapatite and poor surface morphology. This technique is utilized to produce rod like or whiskers nanohydroxyapatite and plate like nanohydroxyapatite. Plate like nanohydroxyapatite is considered wisely because it has the similar morphological features as that of the inorganic mineral of bone [22]. In summary, hydrothermal method to synthesize nanohydroxyapatite is the effective method to design or generate pure identical crystals of nanohydroxyapatite with required morphological features and narrow size distribution.

· Yan et al. [23] detailed a successive process of hydrothermal treatment using surfactants (SDS and CTAB) for the better nucleation and crystal growth of HAP.

· Riman et al. [24] detailed the synthesis of nanohydroxyapatite by low temperature hydrothermal and mechanochemical hydrothermal method.

· Wang et al. [25] detailed the hydrothermal method using cationic surface active agents such as CTAB (cetyltrimethylammonium bromide) to synthesize nanohydroxyapatite of uniform morphology and sizes.

· Xin et al. [26] detailed the synthesis of nanocrystalline calcium phosphate crystals using simple hydrothermal method with a Ca-EDTA/PO4 solution.

Micro emulsion synthesis method:

A micro emulsion is a clear thermodynamically stable mixture of unmixable H₂O and oil i.e. stabilized by addition of surfactant or surface active agents. Usually, it involves dispersing of H₂O with high dielectric constant in oil with low dielectric constant. Therefore to control interfacial tension between two unmixable phases, inclusion of surface active agents is mandatory. This technique mainly overcomes the disadvantages of producing nanohydroxyapatite which involved agglomeration (chemical precipitation and hydrothermal synthesis method). Particle sizes of nanohydroxyapatite of needle shaped or spherical morphology can be produced by this technique [27].

Figure 3: Transmission electron microscopy of nanohydroxyapatite: (a, b) by chemical precipitation method at 100 and 200nm respectively (c, d) by hydrothermal synthesis method at 50 and 150 nm respectively (e) by micro-emulsion synthesis method.

HOW TO LOAD DESIRED CONSTITUENT TO NANO-HYDROXYAPATITE (nHA)?

To load a component into a molecule and to learn its combined form of effectiveness is interesting set up to deal with and researchers mainly follow this to have an advanced knowledge about the matter they are dealt with. Additionally there are many ways which have been studied to load desired therapeutic constituent into nanohydroxyapatite. There are 2 ways of loading a component into nHA - In-situ loading: in which the therapeutic agents are loaded during the synthesis of nHA (condition- synthesis process to be carried out in high temperature and pressure condition to ignore destruction of drugs). Ex-situ loading: in which the therapeutic agents are loaded after the nHA is synthesized. However, the in-situ loading is the most powerful technique in loading agents into nHA than the ex-situ loading.

Nanohydroxyapatite generated by chemical precipitation and micro emulsion method can undergo in-situ loading. Few examples of reported ways of in-situ loading are given as follows -

· Olton et al. [28] carried out addition of pDNA to calcium precursors before precipitating with phosphate precursors.

· Liu et al. [29] reported needle like nanohydroxyapatite particles by precipitating calcium deficient HA with BSA.

· Apart from protein, various agents such as radioisotope can be loaded by co- precipitation technique and this technique is considered as one of the most simple and economically effective in situ method of loading agents [30].

· The in-situ loading involves micro emulsion technique to load wide range of substance such as inorganic materials and proteins into nHA [31].

Nanohydroxyapatite generated by hydrothermal synthesis method can undergo ex-situ loading and it mainly includes surface adsorption criteria.

· Matsumoto et al. [32] detailed an ex-situ loading in which approximately 0.69 wt% adsorption of cyt-C was done to nHA.

· Kandori et al. reported 0.126 and 5.96 wt% adsorption of BSA and Myoglobin [33] into nHA respectively.

· Presently, Boonsongrit et al. [34] reported adsorption of more than 8 wt% of BSA into hydroxyapatite.

Nevertheless, ex-situ loading has less potential to load therapeutic agents into a nano structured compound than the in-situ loading technique. This is due to demerit involved in ex-situ loading such as easy undergoing desorption, reduced surface site of action due to large adsorption etc.

MODERN APPROACH OF HYDROXYAPATITE IN PHARMACEUTICAL SCIENCE:

1. CANCER:

In a simplest form, one can define cancer as a state of disease in which abnormal cells divide uncontrollably with a capacity to invade and destroy body tissue. Cancer is considered one of the prime sources of death worldwide. As per the 2014 world cancer report, there were approximately 14 million existing cases for cancer and 8.2 million deaths due to cancer. The treatment method used for cancer such as radiations and chemotherapy has unfortunately severe limitations therefore the foremost thought of every researcher is to control or check the growth of cancerous cells [35]. Among all the methods used to treat cancer the recent, best and trending mechanism is to use nanoparticles that can directly strike the cancer cells only. Out of which nanohydroxyapatite has proved to be a charisma in the field of pharmaceutical and medical science due to its resemblance in chemical and physical properties with human bone, teeth or enamel. Effect of HA on cancer cells can be easily studied as it is worthwhile, cost effective, and profitable and is easily available from natural sources such as medicinal plants, egg shells, animal bones, cod fish bones etc.

Many studies on nanohydroxyapatite has been reviewed for cancer therapy by researchers both in vitro and in vivo –

· Liu and his coworkers studied the effect of synthesized nanohydroxyapatite on human liver carcinoma cells (HepG2 cells) [36].

· Li and his coworkers reported the changes occurred after the uptake of nHA [37] and also reported the influence of nHA on hepatoma cells and hepatocellular carcinoma cells respectively [38].

· Additionally, Cao and his coworkers [39] reported the study both in vitro and in vivo, about the mechanism of how the proliferation of hepatocellullar carcinoma cells is inhibited using HA.

· Pathi et al. [40] detailed the features on nHA concluding its effectiveness to treat breast cancer, hepatoma, GI cancer, bone cancer etc.

· Several methods were reported to synthesize mesoporous magnesia [41,42] because of its capacity to kill and inhibit cancer cells like human gastric cancer cells, HeLa, Human liver carcinoma cells etc.

A large number of medicinal plants extract and their active constituents have been outlined as potential anticancer agent. Polyphenols such as phenolic acid, flavonoids, terpenes and alkaloids possess the biological potential to treat cancer [43]. Ursolic acid, oleanolic acid, boswellic aid, pomolic acid, avicins, and fomitellic acid under the category of trierpenoids possess cytotoxic effect [44,45]. Moreover, flavonoids like kaemferol, myricetin, quercetin and rutin possess anticancer activity [46]. Additionally, alkaloids such as matrine and sanguinarine are also screened to possess anticancer activity [47]. Anticancer activity of various plants is given in Table no.1 and the isolated compounds with anticancer activity are given in Table no.2.

Table 1: Anticancer Activity of Various Plants:

Plant	Type of phytochemicals	Biological activity	Reference
Aloe vera	Aloin	Inhibition of neuroecto Dermal tumors	48
Azadirachta indica	Limonoids	Murine erhlich carcinoma (EC)	49
Alangium salviifolium	Isoquinoline alkaloids and derivatives (IAD)	Ehrlich ascites carcinoma	50
Alisma orientale	Triterpenes	Human liver carcinoma cells	51
Alstonia yannanesis	IAD	Colon cancer	52
Aristolochia Manshuriensis	IAD	Bone cancer	52
Aristolochia Cucurbitifolia	IAD	Human liver cancer	52
Berberis vulgaris	Berberine	Breast, liver, colon cancer	53
Brucea javanica	Triterpenes	Bladder cancer	53
Emblica officinnalis	Alkaloids	Antitumor activity	54 - 56
Euphorbia fischeriana	Diterpenes	General treatment of cancer	57
Ginkgo biloba	Terpenoids	Human breast cancer	58 - 60
Hedyotis biflora	Benzopyrone	General treatment of cancer	61
Houpoea obovate	Lignans	General treatment of cancer	61
Ixeris chinensis	Sesquiterpenes	General treatment of cancer	62
Juglans mandshurica	Quinones	Lung cancer	63
Matricaria recutita	Sesquiterpenes	Human HeLa cervix adenocarcinoma cells, K₅₆₂ leukemia cells	64
Piper longum	Amide alkaloids	HL60 and MCT-7 cell lines	65, 66
Withania somnifera	Alkaloids	Dalton’s ascitic lymphoma	67

Table 2: ISOLATED COMPOUNDS AND THEIR ANTICANCER ACTIVITY

Medicinal plant name	Isolated compounds	Anticancer activity	Reference
Taxus baccata	Cabazitaxel	Metastatic castration – resistant prostate cancer	68
Colchium autumnale	Colchicine	Multiple solid tumors	69
Combretum caffrum	Combretastatin	Human breast cancer	70
Glycyrrhiza uralensis	Isoliquiritigenin	Human NSCLC, A549 Lung Cancer cell line	71
Needles of yew trees	Larotaxel	Metastatic breast cancer, Bladder cancer, HSCLC, pancreatic cancer	72
Podophyllum peltatum	Podophyllotoxin	Lymphomas, bronchial and testicular cancer	73
Polygonum root, peanut seeds,berries and grapes	Resveratrol	HepG2 cell line, colorectal tumor	74
Broussonetia papyrifera	2S-abyssinone II verubulin	Gliobastoma, brain tumors	75, 76
Catharanthus roseus G. Don	Vinblastine, Vincristine, Vindesine, Vinflunine	Lymphocytic leukemia	77
Taxus brevifolia	Paclitaxel	Breast cancer, ovarian cancer, NSCLC	77
Taxus species	Docetaxo	Breast cancer, ovarian cancer, non small scale lung cancer (NSCLC)	77
Periwinkle plant	Vinorelbine	Advanced breast cancer, advanced NSCLC	78

2. ORTHOPEDICS:

Hydroxyapatite is used as a versatile biomaterial in orthopedic application and this biomaterial or biomedical material is either used as a single entity or is packaged or designed with some medical devices to treat certain bone disease or disorders by directly counteracting with the etiology of the diseases [79,80]. Bone diseases can be caused by both internal and external causes or can be inherited from parents or may be caused due to accidents, therefore in last few decades excess demands and requirements for synthetic bone substitute and supplements is observed. Recent techniques such as bone grafting and cell engineering have proved to be an advantage in the orthopedic application [81]. The identity of vertebrates is characterized due to presence of bone which is composed of various minerals, of which microscopic crystals of calcium phosphate i.e. hydroxyapatite is the chief mineral having wide applications. Apart from the calcium phosphate other variety of minerals are also present in the bone such as dicalcium phosphate (DCP), tricalcium phosphate (TCP) and some amorphous phases of calcium phosphate which is essential for bone to maintain its rigidity and texture [82]. Figure 4 shows various components of bone morphology [83] and figure 5 shows cells like osteogenic cells, osteoblasts, and osteocytes [84]. HA due to its chief property of being bioactive in nature, it has a remarkable effect and capacity to integrate through bones and provide support to it.

Figure 4: Various components of bone morphology [83].+

Figure 5: Showing osteogenic cells, osteoblasts cells and osteocytes [84].

Hydroxyapatite used in bone grafting:

There are three essential properties which are needed to be possessed for generation and maintenance of bone i.e. providing support for osteoconduction, providing growth factors for osteoinduction and stimulating osteogenesis. Presence of the entire three characteristic can be easily found in an autogenous bone therefore it is used as the best material in bone grafting techniques [85,86]. In bone grafting techniques hydroxyapatite is a biomaterial which is cost effective and easily available therefore it is worthwhile to consider it as good substitute [87,88].

Hydroxyapatite used in spinal fusion:

Hydroxyapatite has a variety of application in spinal surgery. Clinically it has been proved that hydroxyapatite is effective bone graft adjuvant in the treatment of childhood scoliosis and spine disorders [89].

Hydroxyapatite used in bone healing and repairs:

Hydroxyapatite is a biomaterial which is osteoconductive in nature and has physiochemical properties similar to the mineral constituents of bone therefore used widely in bone repairs and bone healing [90]. Oral administration of calcium hydroxyapatite can be effective for bone repair [91].

Hydroxyapatite used in osteoporosis:

Osteoporosis is defined as one of the bone disease in which the bone weakness increases and thus increasing the risk to break. It has been proved that the natural microcrystal of nano calcium HAp can be substituted in order to prevent osteoporosis. Oral administration of calcium HAp can prevent osteoporosis because evidence shows that calcium HAp is better absorbed than calcium supplements [91].

Hydroxyapatite used in rheumatoid arthritis:

Drugs are often loaded or incorporated into hydroxyapatite nanoparticles to treat rheumatoid arthritis. For example - for the treatment of rheumatoid arthritis methylprednisolone acetate-loaded hydroxyapatite nanoparticles were effectively used [92].

3. ORTHODONTICS:

Tooth enamel is considered as the hardest mineral constituent of human body than the bone which mainly provides protection from decay. Of the total composition of enamel 96% constitutes the inorganic material and only 5% constitutes organic material and water whereas the dentin constitutes 70% of the inorganic material. HA is also one of the chief mineral of enamel, which provides tooth enamel rigidity and white shiny appearance. Nowadays nanohydroxyapatite has been used lately as a main component in the field of restorative dentistry [93].

Figure 6: Structure showing enamel and dentin [94].

We know that HA has been a study of interest for a long period due to its biocompatibility and bioactivity nature with human bone and teeth. So it is used as remineralising agent for counteracting demineralised areas of enamel and dentin, as it already contains elements calcium and phosphate. It has now been currently known that nanohydroxyapatite of size ranging from some 500 – 1000nm can be used in dentistry or the treatment of plaques and cavities. It can also be contained in the toothpastes s it has good capacity to bind with the proteins. Furthermore it can also be used as a filling material or fillers to fill the pores in the teeth.

For the very first time HA came to an interest as remineralising agent to the Japanese company called Sangi Co. Ltd. They developed a toothpaste containing nanohydroxyapatite (Apadent) and the first toothpaste having similar remineralising activity to HA be discovered in 2006 at Europe [95].

In its granular form, hydroxyapatite is currently used in clinical dental practice to reconstruct periodontal bone defects, to the fill bone defects after cystectomy, after apicoectomy, after the loss of dental implants and to increase of the thickness of atrophic alveolar ridges. Shaped blocks of hydroxyapatite are especially used in maxillofacial surgery (bone defects after trauma, osteotomies and reductive stabilization, reconstruction of facial skeleton, replacement of parts of orbital and maxillary bone). Blocks, as well as granular powder, can also be used in pre-prosthetic surgery to increase the thickness of the alveolar ridge.

Many studies have been conducted on nHA used in orthodontics applications, which are as follows –

· Moshaverinia et al. [96] reported the anticariogenic effect of glass ionomer cements (GIC) on teeth by the addition of N-vinyl pyrrolidone containing acids, nanohydroxyapatite and fluorapatite.

· Huang et al. [97,98] detailed the remineralizing effect of nHA on demineralized bovine enamel.

· Hangoo et al. [99] detailed his study on dental erosion due to heavy intake of carbonic acid containing drinks, beers etc.

· Masahiro et al. [100] conducted study for the analysis of nano-polymorphic crystalline HA as a co-adjuvant material in oral surgery.

· Singh et al. [101] in his study reported the osteoblastic activity of nano-polymorphic crystalline HA.

· Qu et al. [102] reported the use of a bioactive and osteoconductive compound formed by nanohydroxyapatite and polyamide 66 (nHA/PA66).

4. ANTIMICROBIAL ACTIVITY:

Medicinal plants are the chief sources of deriving a drug used to treat cancer as it contains varieties of active constituents like alkaloids, flavonoids, triterpenoids etc which has an important role and proven effect used in the formulation of anticancer drugs. These isolated compounds from the plant sources are tested for its effectiveness against cancer both in vivo and in vitro. Some of these compounds exert their cytotoxic effect by inhibiting cancer cell growth. Nano-hydroxyapatite are generally prepared by green synthesis using varieties of available plant extracts and tested for its antibacterial activity against microorganisms. Hence, green synthesis can be an effective method of developing nHA with antibacterial properties [103].

Various studies were performed involving hydroxyapatite preparation and checked for antimicrobial activity such as –

· Jian yu et al. developed a biomaterial (hydroxyapatite whisker HAPw) having antimicrobial bone restorative property and was tested against Escherichia coli, Staphylococcus aureus, Candida albicans, Streptococcus mutans [103].

· GS kumar et al. reported the green synthesis of hydroxyapatite nanorods from plants Azadirachta indica and Coccinia grandis and tested for its antibacterial activity against Escherichia coli and Staphylococcus aureus [104].

· Yang t al. [105] recently reported about HA carriers for vancomycin.

· Ferraz et al. [106] detailed HA for controlled release of β-lactam antibiotics.

· Queiroz et al. [107] detailed his work based on HA reinforced with ampicillin.

· Forsgren et al. [108] successfully achieved kinetics of cefalotin and bisphosphonate.

CONCLUSION:

This review work mainly describes the nano structure of hydroxyapatite and its modern approach in pharmaceutical sciences. Hydroxyapatite is a naturally occurring inorganic mineral constituent of the bone and due to its chemical and physical similarity with human hard tissue; it has a wide application in the field of orthopedics and orthodontics. We often know that, medicinal plants are the major sources of active constituent’s used for the treatment of various types of disorders and diseases, including numerous forms of cancer. The active compounds isolated from medicinal plants may not specifically function as anticancer agents or drugs but may provide alternatives for the advancement of prospective cytotoxic agents. As research progresses, new technologies will aid in the improvement of the anticancer activities of drugs. Nanotechnology is a trending field related to nanoparticles, which have greater potential than normal-sized compounds. Nano hydroxyapatite formed using plant extracts are reported to possess anticancer effect due to their large surface area, which enables efficient drug delivery. However, most of the studies using nanohydroxyapatite prepared from extracts of medicinal plants have been conducted both in vitro and in vivo. Therefore, nowadays researches are more emphasized based on the studies involving green synthesis of nanoparticles. This review will help you to know more about various synthesis method of nanohydroxyapatite, its structure and its application.

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Received on 08.11.2018 Modified on 19.12.2018

Research J. Pharm. and Tech. 2019; 12(3): 1463-1472.

DOI: 10.5958/0974-360X.2019.00243.9