Polymeric and Ceramic Nanoparticles:Possible Role in Biomedical Applications

Shikha Kaushik

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Polymeric Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Biomedical Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Ceramic Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Biomedical Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

AbstractNanotechnology is an emerging field that deals with the study, design, andapplication of materials with structural features having at least one dimensionin the nanometer range (1–100 nm). The unique size-dependent properties ofnanoparticles make them potential candidates for their applications in differentareas, ranging from environmental science to an emerging multidisciplinaryfield that includes chemistry, physics, biology, and medicine. Therefore, it isvery important to understand their nature at cellular and biomolecular level.The interaction of nanoparticles with biological macromolecules, such as proteinand DNA, proved to be beneficial in therapeutic fields ranging from moleculardiagnostics and biosensors to drug discovery, gene/protein delivery, and drugdelivery.

Literature is rich in reports illustrating the role of polymeric and ceramicnanoparticle in numerous diagnostic, pharmaceutical, and medical fields becauseof a number of properties associated with them such as good biocompatibility,easy design, chemical inertness, and high heat resistance. Various natural andsynthetic polymers are used to synthesize polymeric nanoparticles (PNPs), and

S. Kaushik (*)Department of Chemistry, Rajdhani College, University of Delhi, New Delhi, Indiae-mail: Kaushik.shikha@gmail.com

© Springer Nature Switzerland AG 2020C. M. Hussain, S. Thomas (eds.), Handbook of Polymer and Ceramic Nanotechnology,https://doi.org/10.1007/978-3-030-10614-0_39-1

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the mostly employed synthetic biocompatible polymers are polyethylene glycol(PEG), polylactic acid (PLA), and poly(lactic-co-glycolic acid) (PLGA).The different types of ceramic nanoparticles (CNPs) used are titania-basedceramics, alumina ceramics, calcium phosphate (CaP), tricalcium phosphate(TCP), hydroxyapatite (HAP), calcium sulfate and calcium carbonate, and bio-active glass ceramics. Among all the areas of polymer and ceramics nanoparticleapplications, the most explored one is the biomedical field. Both PNPs and CNPshave been employed as drug delivery agents against various diseases, includingcancer, because of their biocompatibility with cells and tissue. Understandingtheir potential biomedical applications at the molecular level will provide majorinsight into its future developments and can hold a promising future in numerousareas of health and medicine.

KeywordsBioceramics · Biomedical applications · Cancer · Ceramic nanoparticles ·Drug delivery · Hydroxyapatite · Nanobiomaterials · Nanocapsules ·Nanospheres · Polymeric nanoparticles

Introduction

Nanotechnology and nanomaterials have now become the common words that areused not only by the researchers but also by an individual in daily life. Nanotech-nology is a fascinating field of research since decades, and a galaxy of scientistsacross the globe are devoting their attention to discover various nanomaterialshaving numerous applications. The concept of nanoscience and nanotechnologywas first presented by Nobel Laureate Richard P. Feynman during his talk entitled“There’s Plenty of Room at the Bottom” at an American Physical Society meeting atthe California Institute of Technology, on December 29, 1959 (Feynman 1960).However, the term “nanotechnology” was first coined by Professor Norio Taniguchiin 1974. He wrote “Nano-technology mainly consists of the processing of separa-tion, consolidation, and deformation of materials by one atom or one molecule”(Taniguchi et al. 1974).

Nanoparticles (NPs) can be defined as solid colloidal particles with size rangefrom 10 to 1000 nm; however, for nanomedical application, the preferential size isless than 200 nm (Biswas et al. 2014). Over the last few years, nanoparticles havereceived significant attention due to their numerous biomedical applications such asdrug/gene delivery, biosensing, bioimaging, bioelectronics, and for antimicrobialactivities. The main objective of NPs is to release the therapeutic molecule, whichcan be drug, oligonucleotide, or proteins directly into the target organ or tissue.Nanoparticles (NPs) can be divided into different categories depending on thecomposition, morphology, physical property, and surface chemistry. On the basisof origin, nanoparticles can be mainly divided into two main categories: organic andinorganic NPs (Fig. 1). Micelles, liposomes, dendrimers, solid lipid nanoparticles,and hybrid and compact polymeric NPs are examples of organic nanoparticles. Thesecond group includes gold nanoparticles, silica, fullerenes, and quantum dots.

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Nanomaterials which can be utilized for various biological and biomedicalapplications are termed as nanobiomaterials. A variety of nanobiomaterials havebeen synthesized and characterized by researchers to determine their potentialities astherapeutic tools (Chen and Thouas 2014).

The nanobiomaterials (NBMs) can be classified into the following subgroups:

• Organic/carbon NBMs• Ceramic NBMs• Polymeric NBMs• Organic inorganic hybrid NBMs• Metallic-based NBMs• Semiconductor-based NBMs• Silica-based NBMs• Biological NBMs• Self-assembled NBMs

In this chapter, we have emphasized on biomedical applications of polymeric andceramic nanoparticles.

Fig. 1 Schematic representation of types of nanoparticles

Polymeric and Ceramic Nanoparticles: Possible Role in Biomedical. . . 3

Polymeric Nanoparticles

Polymers are macromolecular structures which are made up of large number ofmonomer units which differ in composition, structures, functionalities, and proper-ties. These variations in properties and compositions of polymers are being used togenerate polymer-based nanoparticle for biomedical applications. The use of poly-meric nanoparticles is not only restricted to drug delivery, but they are also used inbiosensing and bioimaging and as a diagnostic tool in medicine. The generation anduse of polymeric nanoparticles have received enormous attention in the recent pastdue to their specificity, efficiency, and most importantly, nontoxicity. Researchershave developed various methods for the preparation of nanoparticles for drugdelivery depending on how to load the drug onto the nanoparticle. The resultingnanoparticle-drug compounds can have the structure of capsules (polymeric nano-particles), dendrimers (hyperbranched macromolecules), or polymeric micelles(Moreno-Vega et al. 2012). The ideal requirements for designing polymeric carrierfor nanoparticles are its ease to synthesize, good biocompatibility, biodegradability,flexibility, nontoxicity, and solubility. Polymeric nanoparticles offer several advan-tages compared to other delivery systems, which are as follows:

• They can deliver a higher concentration of therapeutic agent directly to a desiredtarget/location which minimize toxicity.

• Polymeric nanoparticles are highly effective or efficient in comparison to oral andintravenous methods of administration.

• Polymeric nanoparticles protect drugs/bioactive molecules against enzymatic andhydrolytic degradation.

• The choice of polymer made them a promising tool for various medical applica-tions such as cancer therapy, delivery of vaccines, and site-directed antibiotics.

• PNPs can also be employed for tissue engineering.• Drug-nanoparticle system also possesses the ability to cross the blood-brain

barrier (BBB).

Polymeric nanoparticles can be classified as biodegradable PNPs and non-biodegradable PNPs. However, depending on the method of preparation, polymericnanoparticles can be categorized into two categories (Fig. 2):

1. Nanocapsules2. Nanospheres

• Nanocapsules: These are the submicroscopic drug carrier systems composedof an aqueous/oily core surrounded by a thin polymeric membrane withspecific properties. The membrane may be composed of natural or syntheticpolymers. The active material is dissolved in the inner core but can also beadsorbed to the surface.

• Nanospheres: Nanospheres involves the matricial organization of polymericchain where drug can be dispersed, entrapped, dissolved within, or adsorbedon the nanoparticle.

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The polymer used for the preparation of nanoparticles can be natural hydrophilicpolymer or synthetic hydrophobic polymer. Natural polymers such as proteins(albumin, gelatin, lectin, legumine, and viciline) and polysaccharides (agarose,chitosan, dextran, alginate, agarose, and pullulan) have been used in the deliveryof oligonucleotides, proteins, and drugs. Synthetic hydrophobic polymers can beeither pre-polymerized or polymerized in the process. The first category includespolystyrene, poly E-caprolactone, polylactic acid (PLA), and poly (lactide-co-glycolide) (PLG). Poly(isobutyl cyanoacrylates) (PICA), poly(butylcyanoacrylates)(PBCA), and poly(methyl methacrylates) (PMMA) fall under the second category.These molecules can be easily excreted from the body and are nontoxic. Differenttypes of polymers used to encapsulate drug are poly(amino acids), polyamides,polyanhydrides, polyesters and polyorthoesters. The choice of material (natural/synthetic) for preparing nanoparticles depends on several factors like the size andsurface parameter of the particle desired and solubility and stability of drugs. Avariety of natural and synthetic polymers are available for formation of nanoparticle,but certain factors like biocompatibility, toxicity, and biodegradability needed to betaken care of while considering them for drug delivery (Fig. 3).

In the recent times, various methods have been developed by the researchersfor the preparation of polymeric nanoparticles. These can be divided into differentclasses like polymerization-based methods, polymer precipitation methods,

Fig. 2 Different types of polymeric based nanoparticles (nanocapsule and nanospheres)

Polymeric and Ceramic Nanoparticles: Possible Role in Biomedical. . . 5

or cross-linking methods. The mode of preparation of PNPs plays animportant role to achieve the desired properties for a particular application.The polymerization method includes polymerization of monomers, dispersionpolymerization, interfacial condensation polymerization, emulsion, and interfacialcomplexation. Solvent extraction/evaporation, solvent displacement, and salting outare some of the methods based on precipitation of polymer. Heat- and chemicalcross-linking are preferred for the amphiphilic macromolecules.

Biodegradable polymers and their copolymers are used to prepare polymericnanoparticles and to encapsulate the active ingredients. Micelles, capsules, fibers,colloids, dendrimers, and nanospheres are some of the multifunctionalized poly-meric nanoparticles. Micelles were the first PNPs developed for therapeutic purpose.

For therapeutic applications, the drug, free or encumbered into nanoparticles, hasto reach the target site, which can be at cellular or molecular level. There are certainbarriers which need to be encountered while delivering these nanoparticle systems.These barriers can be classified into external (skin and mucosa), en route (bloodand extracellular matrix), and cellular barriers (the limited cellular uptake, endo-somal/lysosomal degradation, and the inefficient translocation to the targetedsubcellular organelles) (Elsabahya and Wooleya 2012).

The important step after preparation of PNPs is the release of drug to the targetsite. The kinetics of drug release is a function of structural, physical, and chemicalproperties of the PNPs. It depends on a number of factors like size, density, porosity,

Fig. 3 Factors to be considered for designing polymeric nanoparticles for drug delivery

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and morphology of polymer as well as on pH, enzymes, and polarity of the solvent.The drug carried by the polymeric nanoparticle to the target site can be released byany one of the physicochemical methods given below (Ghosh 2000) (Fig. 4):

• The polymeric nanoparticle gets swollen by hydration mechanism which leads tothe release of drug through diffusion.

• Release of drug from particle surface.• The enzymatic cleavage resulted in the degradation of the polymer at the site of

delivery resulting in the release of drug from the entrapped inner core.

Biomedical Applications

Cancer is a deadly disease, which occurs due to the uncontrolled/abnormal growth ofthe cells. Since many factors are known to cause cancer, hence a single technique ortherapy is not sufficient for the complete eradication of cancer. Various therapieshave been put forward for the treatment of cancer; however, they are associated withthe severe side effects, such as non-specificity and toxicity of the drug, and chemo-therapy is one of them. The development of nanoparticles proved to be beneficial bydelivering drug to the tumor site and hence minimizing the toxic effects to othernormal tissues and organs. Figure 5 shows a schematic representation of the bio-medical applications of polymeric and ceramic nanoparticles. Magnetic nano-particles, either coated with gold or polymers, are used to deliver the drug to a

Fig. 4 Mechanism of drug release from polymeric nanoparticle (PNPs) (i) release from the surface,(ii) diffusion through the swollen polymer matrix, and (iii) release due to erosion

Polymeric and Ceramic Nanoparticles: Possible Role in Biomedical. . . 7

specific location. Several other drug delivery systems have been tested byresearchers against cancer. Micelles and liposomes are considered as good drugcarrier for the delivery of chemotherapeutic agents. Micelles have hydrophobic coreand hydrophilic shell which makes the insoluble drug soluble and hence can beeasily carried across the membrane. While several anticancer drugs are under clinicaltrials, Genexol-PM (paclitaxel), has been approved by US FDA and is being used forthe treatment of breast cancer (Oerlemans et al. 2010). Alginate (an anionic poly-saccharide)-based nanoparticles have been widely used for drug delivery. Such PNPdelivery system was developed for antitubercular drugs (ATDs) and is shown toexhibit high drug encapsulation efficiency, ranging from 70% to 90% (Reis et al.2006).

Researchers have encountered many problems while developing/testing drugs forvarious diseases. MDR (multiple drug resistance) is considered as a serious problemin chemotherapy, which arises mainly due to the overexpression of the plasmamembrane glycoprotein (Pgp). The use of colloidal carriers has been applied inorder to restore the effectiveness of anticancer drugs against tumor cells and henceoutwitting Pgp-mediated MDR.

Various strategies have been employed for the development of NPs targetingthe brain because of the great difficulty for drugs to cross the blood-brain barrier(BBB). Nanoparticles are shown to cross BBB by endocytosis/phagocytosis. Thenanoparticle targeting the brain is based on its interaction with certain specificreceptor-mediated transport systems in the BBB. A study has shown that poly(butylcyanoacrylate) nanoparticles successfully delivered hexapeptide dalargin,doxorubicin, and other active agents into the brain (Kreuter 2001).

Recent advancement in research has found that a large number of bioactivemolecules and vaccines are based on peptides and proteins. For example, a studyon diabetic rats has shown that insulin-loaded nanoparticles have reduced the bloodglucose level and preserved insulin activity for up to 14 days when administeredorally (Pathak and Thassu 2009) (Fig. 5).

Fig. 5 Schematic diagramshowing biomedicalapplications of polymeric andceramic nanoparticles

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Dendrimers are nano-sized, highly branched macromolecules which are charac-terized by the presence of internal cavities and a large number of functional groups.The presence of functional groups is responsible for their high solubility, miscibility,and high reactivity. These structural features serve as a center for the attachment ofdrugs. Dendrimer based therapeutic nanodevice has been reported for the successfullocalization and delivery of an anticancer drug methotrexate through a folate recep-tor (Quintana et al. 2002).

AIDS (acquired immune deficiency syndrome) is a life-threatening diseasecaused by human immunodeficiency virus (HIV), damaging an individual’s immunesystem. The first treatment suggested for this disease involves the intake of 30–40pills a day, which gets reduced to a few with the advancement in medicine (Bartlettand Moore 1998). Studies have suggested that this therapy has become even moreeffective with the development of polymeric nanoparticles which deliver antiretro-viral (ARV) drugs intracellularly (Mamo et al. 2010). Nanotechnology also plays acrucial role in delivering the antiretroviral drugs, foiling HIV infections, anda number of reports have demonstrated the role of polymeric nanoparticle systemfor the successful delivery of anti-HIV medications to the targeted site (Nowacek etal. 2010; Jayant and Nair 2016).

Researchers have used poly(lactic-co-glycolic acid) (PLGA) nanoparticlesencapsulating three antiretroviral drugs, ritonavir, lopinavir, and efavirenz (Destacheet al. 2009). This study has shown that nanoparticle system has sustained drugrelease for over 4 weeks (28 days), whereas free drugs were eliminated within48 h (2 days). Therapeutic applications of various PNPs with drugs and polymersused in the formulation are shown in Table 1.

Ceramic Nanoparticles

Nanoceramics have received significant attention in the recent past due to theirunique processing, mechanical strength, toughness, bioactivity, and controllablecrystallinity. They can be easily prepared with desired size, shape, and porosity.Among the varieties of nanomaterials, nanostructured ceramics (or nanoceramics)are being considered for major applications in orthopedic and dental treatments.Biocompatible ceramics, also known as bioceramics, consist of both macro- andnanomaterials, and their development has hastened in the last few years.Bioceramics are mainly used for bone, teeth, and other medical applications.Inorganic material can be classified into ceramic and metallic nanoparticles. Ceramicnanoparticles (CNPs) exhibit properties between that of metals and non-metals.Moreover, their magnetic, optical, and biological properties provide substantialopportunities to study and control biological processes. Figure 6 shows differenttypes of widely used ceramic nanoparticles.

Nanoceramics, such titanium oxide (TiO2), alumina (Al2O3), hydroxyapatite(HA), zirconia (ZrO2), and silica (SiO2), have been prepared by various syntheticpathways to improve their physicochemical properties so as to reduce their toxiceffects in biological systems. Certain characteristics such as high stability, the ease

Polymeric and Ceramic Nanoparticles: Possible Role in Biomedical. . . 9

with which they can be incorporated into hydrophobic and hydrophilic systems, highloading capacity, and various administration routes make CNPs a potential tool in drugdelivery. Nonetheless, studies have shown the adverse response of CNPs in varioustissues, including the immune system. Drug delivery at a controlled rate, size and doseof drug are considered important in biomedicine. Some of the widely used ceramicnanoparticles and their therapeutic applications are shown in Table 2.

Biomedical Applications

Calcium plays a vital role in the body, and it is necessary for normal functioning ofbones, muscles, nerves, and cells (Balasubramanian et al. 2017). The calciumphosphates occur abundantly in nature in several forms as:

Table 1 Therapeutic application of various polymeric nanoparticles (PNPs)

Polymer Drug Therapeutic role Reference

Albumin Albendazole Ovarian cancerTreatment

Noorani et al.2015

Biodegradable diblock copolymerof poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG)

– Gene delivery atmucosal surfaces(cervicovaginal)

Tang et al.2009

Polyvinylpyrrolidone/celluloseacetate butyrate binary blend

Acyclovir Antiretroviral Naik andRaval 2016

Poly(lactide-co-glycolide) (PLG) Rifampin,isoniazid, andpyrazinamide

Tuberculosis (TB)treatment

Gelperinaet al. 2005

Poly(e-caprolactone) andhydroxypropyl-b-cyclodextrin

Indomethacin Topicalapplication (anti-inflammatory)

Elmowafyet al. 2017

Poloxamer F68 Albendazolesulfoxide

Cysticechinococcosistreatment

Ahmadniaet al. 2013

Poly(methyl methacrylate) – Vaccine adjuvant(oral/IMimmunization)

Jawahar andMeyyanathan2012

poly (lactide-co-glycolide) (PLG). – ReverseParkinson,Huntingtondisease treatment

Cheng et al.2015

Chitosan Tramadol HCl Depressiontreatment

Kaur et al.2015

Poly(alkyl cyanoacrylate) Antibacterial,steroids, anti-inflammatoryagents

Ocular delivery(glaucomatreatment)

Jawahar andMeyyanathan2012

Poly (lactide-co-glycolide) (PLG)nanoparticles coated with cationiclipid

Small-interferingribose nucleicacid (siRNA)

Treatment ofchronicinflammation ofpsoriasis

Cheng et al.2015

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Fig. 6 Different types of widely used ceramic nanoparticles

Table 2 Widely used ceramic nanoparticles and their therapeutic application

Polymer Therapeutic application Reference

Calcium phosphate Anticancer drug delivery Paul and Sharma 2003

Photodynamic therapy Seong and Kim 2015

Bone disease and bone repair Rawat et al. 2015

Gene delivery Ardekani et al. 2014

Tricalciumphosphate

Bone implant and replacement Wong et al. 2002

Tissue engineering Sánchez-Salcedo et al. 2008

Hydroxyapatite(HAP)

Dentistry and orthopedics Mendelson et al. 2010

Silicon-substitutedHAP

Bone-repairing devices; drug deliverysystems

Vallet-Regí and Balas 2008;Cerruti 2012

Calcium sulfate Orthopedics and dentistry Thomas and Puleo 2009

Bioactive glasses(BG)

Bone tissue engineering Hum and Boccaccini 2012

Calcium carbonate Anticancer agent Wu et al. 2014

Gene delivery Wang et al. 2014

Silica nanoparticles Anticancer drug delivery/diagnosticimaging

Chen et al. 2014

Gene delivery Lin et al. 2014

Titania-basedceramics

Cancer therapeutics Zhang et al. 2012

Zirconia ceramics Drug delivery, dentistry Wang et al. 2013

Alumina ceramics Dentistry; arthroplasty; antimicrobialactivities

Seil and Webster 2012

Polymeric and Ceramic Nanoparticles: Possible Role in Biomedical. . . 11

(a) Monocalcium phosphate Ca(H2PO4)2 occurring as monohydrate(b) Dicalcium phosphate CaHPO4 named as dihydrate(c) Tricalcium phosphate Ca3(PO4)2, also named as calcium orthophosphate(d) Hydroxyapatite Ca5(PO4)3(OH)(e) Apatite Ca10(PO4)6(OH, F, Cl, Br)2(f) Octacalcium phosphate Ca8H2(PO4)6. 5H2O(g) Tetracalcium phosphate, Ca4 (PO4)2O

Hydroxyapatite (HAP), Ca10(PO4)6(OH)2, a type of calcium phosphate, is themajor inorganic component of bone and teeth in mammals. The bones are composedof biological apatite and molecules of collagen. HAP exhibit the structure similarto that of bone mineral and hence possess excellent bioactivity, bioresorbability,biocompatibility, and high affinity to drugs, proteins, and antigens. These physico-chemical properties should be adapted in synthetic HAP crystals to optimize theirspecific biomedical applications (Moreno-Vega et al. 2012). Calcium phosphates areused as a carrier for variety of biological agents such as proteins, enzymes, antigens,drugs, and non-viral gene delivery. These are also being used for the treatment ofcancer. These nanoparticles are abundant in nature, especially in calcified tissues ofvertebrate and in dental field, which has shown tremendous results in theremineralization of teeth. The nano-HAP is considered for surgical implantation inbone defect, and currently, calcium phosphate-based bone cements are used for bonerepair after surgery. Additionally, it can be used as a delivery tool for antibiotics. Ithas been reported that HAP can also combine with other chemical agents ormaterials to enhance its therapeutic effect (Sarath Chandra et al. 2012). Panseri etal. prepared superparamagnetic iron HAP-nanoparticles, and these systems wereshown to possess excellent biocompatibility and an increased osteoblastic cellproliferation when exposed to a static magnetic field (Panseri et al. 2012). Studieshave also shown that HAP can also be used to inhibit the proliferation of tumors(hepatoma). The effect of HAP nanoparticles on the cell line BEL-7402 at differentdoses was studied. Results revealed that a dose of 29.30 mg/mL of HAP-nanopar-ticle inhibited the growth, whereas when treated with a dose in between 30 and200 mg/mL, it showed antiproliferative and proapoptotic effect using diverse tests(Liu et al. 2003) (Fig. 6).

A pH-responsive targeted drug delivery system was prepared by Zhao et al. bycombining HAP with magnetite and mesoporous silica (Zhao et al. 2013). Resultsrevealed that the dissolution of hydroxyapatite under acidic conditions triggers therelease of the loaded drugs in Fe3O4@mSiO2@HAP nanoparticles. On similar lines,Li et al. 2015 have shown that lactobionic acid-conjugated bovine serum albuminwas combined with hydroxyapatite via 4-carboxyphenylboronic acid to developa pH-sensitive drug delivery system. At low pH, an increase in cell uptake in livercarcinoma cells was observed (Li et al. 2015).

Similar to calcium phosphate nanoparticles, calcium carbonate nanoparticles arealso present in nature in substantial amount, e.g., in bones, egg shells, etc. They haveseveral advantages like great biocompatibility, low cost, easy fabrication in tonanoparticles, slow biodegradability, etc. These systems have also been used for

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the delivery of drugs, proteins, and anticancer agents. Researchers have also studiedpH-sensitive nanocomposites by combining different materials. One such work hasbeen reported by Liang et al. where pH-sensitive nanoparticles containing doxoru-bicin were prepared by combining heparin, biotin, calcium carbonate, and calciumphosphate (Liang et al. 2014). Results demonstrated that hybrid nanoparticles caneffectively mediate gene transfection and deliver the drug.

Titania or titanium oxide (TiO2) is another important ceramic material which hasbeen used as drug delivery agent in nanoform for various diseases. The titaniumdioxide nanoparticles have high photocatalytic activity and functional surfacealong with broad dielectric and optical characteristics. The functional surface withdrugs/ligands offer targeting property. These systems are extensively used in phar-macology, and currently, they are also used in photodynamic therapy because of theirtendency to undergo photooxidation. Additionally, their toxicity decreases whenthey are associated with other materials such as HAP. As stated earlier, therapiesused for the treatment of cancer impart adverse effects on the human health. Studieshave shown that TiO2 has been successfully used as a new therapeutic agent forcancer, particularly colon cancer. The human colon carcinoma cells were destroyedwhen they were subjected to photoexcited TiO2-nanoparticle system. Thus, suchsystems were shown to be crucial for the eradication of this deadly disease.

Alumina ceramic (aluminum oxide or Al2O3) is one of the most widely usedadvanced ceramic materials. It is highly stable, strong, and heat-resistant. Aluminumoxide ceramics are mainly used in biomedical fields like dentistry, arthroplasty, andtreatment of hand and elbow fractures and as an antimicrobial agent (Seil andWebster 2012).

Gliomas are a type of tumors that occurs at various locations in nervous systemsincluding the brain and spinal cord. TiO2-PEG system has been shown to be aneffective treatment for malignant gliomas. Wu et al. have shown that mesoporoustitania nanoparticles can be used for drug delivery (Wu et al. 2011). Such systems(mesoporous titania nanoparticles) were prepared via controlled hydrolysis, and theircytotoxic effect was investigated using human breast cancer (BT-20) cell line andMTT assay. Results revealed that these nanoparticle systems exhibited goodbiocompatibility.

Zirconia, ZrO2, is a ceramic material which exhibits tremendous potential inbiomedical field as a drug delivery agent as well as for the manufacturing of medicaldevices. This system has also been used in orthopedics for the manufacturing of hiphead prostheses, and studies suggested no adverse effect was observed uponthe insertion of ZrO2 samples into the bone or muscle. ZrO2 can also be used forpH-sensitive drug delivery systems. However, fewer reports are availablefor this material in comparison to other ceramic nanoparticle system and henceneeds further exploration.

Researchers have also reported the nanomedicine applications of barium titanatenanoparticles (BTNPs). BTNPs are found to be nontoxic even if they are used athigher concentrations, and such systems can effectively work as protein as wellas drug carriers. Ciofani et al. had prepared and characterized polymer/BTNPcomposites for the first time and also discussed their possible applications in tissue

Polymeric and Ceramic Nanoparticles: Possible Role in Biomedical. . . 13

engineering (Ciofani et al. 2011). Boron nitride nanotubes can also be employed astransducers because they exhibit excellent thermal and chemical stability. Thesestudies encourage further exploration in the field of CNPs and their applications inbiology and medicine for therapeutic purposes.

Silica, SiO2, is an important material in biomedical research and has been widelyused as a drug delivery agent. Mesoporous silica nanoparticles (MSNs), prepared bypolymerizing silica in the presence of surfactants, are characterized by ease ofavailability, large surface area and volumes, tunable pore size, ease of dissolution,and encapsulation of drugs/chemical agents (Chen et al. 2013). Additionally, variousfunctional groups/ligands can be attached to the surface of the silica, further increas-ing its biocompatibility and target ability. These nanoparticles are able to store andrelease the drug/ligand to the target site and hence work in a controlled manner.Reports have suggested that multimodal silica nanoparticles work as effectivemarkers in cancer diagnosis and imaging, and they are also found to reduce cellviability by apoptosis. However, toxic behavior of such systems is a matter ofconcern, and this needs to be addressed so that it could be applicable/approved forhuman use.

Conclusions

Application of nanomaterials in several areas of biomedical field has shown remark-able progress and provided a lot of opportunities for the future of nanomedicine.Among these, polymeric and ceramic nanoparticle systems proved to be versatilenanocarriers and exhibit numerous biomedical applications. PNPs play an importantrole in the diagnosis and treatment of a wide range of diseases, for instance, viralinfections, cancer, cardiovascular diseases to pulmonary and urinary tract infections.They not only carry the drug to the target site but also increase the efficacy of drugsin treating diseased tissue. Similarly, ceramic nanoparticles also exhibit numerousapplications in the field of dentistry, orthopedics, anticancer drug delivery, and tissueengineering. They offer several advantages like good biocompatibility, biodegrad-ability, osteoinductivity, resorbability, and hydrophilicity. The ease with whichthese nanoparticles systems can be prepared and implemented endorses their futuredevelopment and success. Although multiple types of PNPs and CNPs are availablein the market, further studies are yet to be done. Various issues associated with theuse of PNPs, like toxicity, immunogenicity, route of administrations, dissociationof polymers, and their clearance, should be taken care of for the safety of patients.Understanding of the potential biomedical applications of such systems will providea major insight into their future developments.

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