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Nanocarriers Used Most in Drug Delivery and Drug Release: Nanohydrogel, Chitosan, Graphene, and Solid Lipid/Ilac Dagitim ve Ilac Saliminda En Cok Kullanilan Nanotasiyicilar: Nanohidrojel, Kitosan, Grafen ve Kati Lipit.


Materials that have one or more dimensions lower than 100 nm are considered nanomaterials. (1) To be more specific, in 2011 the European Commission defined a nanomaterial as follows:

"A natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm-100 nm." (2)

Nanomaterials have great research and development/product development potential in medical applications. Some of these applications include DNA/RNA nanotechnology, diagnosis by molecular imaging, biosensing, nanomedicine, and nanocarriers for drug delivery. (3) A considerable number of nanomaterials have been developed, produced, and utilized for these application fields, such as nanohydrogels, chitosan/starch/cellulose nanoparticles, graphene (GR)/GR oxide (GO) nanosheets, iron oxide nanoparticles, gold nanoparticles, cerium oxide nanoparticles, and carbon nanotubes/nanoparticles.

Nanomaterials exhibit extraordinary optical, electronic, and/or mechanical properties when compared with their greater scaled forms. They can differ in color, conductivity, reactivity, surface area to volume ratio, and surface tension from macro forms. Due to this, nanomaterials have attracted the attention of scientists for their potential utilization in vaccines, drug development, and drug delivery. (4) Over many years, many nanomaterials have been adopted as nanocarriers, i.e. nanohydrogels, oil-in-water (O/W) emulsions, liposomes, and nanoparticles based on synthetic polymers or natural macromolecules. (5) The very first studies were conducted by Couvreur et al. (6) and Kreuter and Speiser. (7) in the late 70s, where the team exploited polymeric nanocapsules as lysosomotropic carriers and adjuvants.

Drug nanocarriers usually serve two main purposes: targeted drug delivery to specific tissue, organ, or cells and controlled drug release. The foundation of drug delivery is based on biocompatible nanoparticles or nanocapsules and targeting molecules. Biocompatible materials are selected and incorporated to enhance the hydrophilicity of hydrophobic carrier systems or drugs. Targeting molecules are generally antibodies or avidin/biotins that directly target tissue, organs, or cells. Drug release features of nanocarrier systems are provided by the environmentally sensitive structure of the carrier. Controlling drug release ensures paramount therapeutic effect by releasing the delivered drug with high efficiency in the targeted area and preventing any healthy tissue damage that could be caused by some drugs such as chemotherapy agents. (8) Nanocarriers that have been designed from polymer-based nanoparticles are solid colloidal particles that are approximately 10-500 nm in size. (4) Drug incorporation into nanocarriers is based on 5 methods: dissolution, entrapment, adsorption, attachment, or encapsulation. (9) Herein a brief review of nanocarrier systems is given. A summary of the literature including easily manipulated popular nanomaterials that have been adopted as nanocarriers (nanohydrogels, chitosan (CS) nanoparticles, GR/GO nanocarriers, and solid lipid nanoparticles) is given. Nanohydrogels and CS nanoparticle derivatives are the most heavily rotated amphiphilic nanocarrier materials. GR/GO nanomaterials are favored nanocarriers since they are present in a wide range of carrier designs. Finally, solid lipid nanocarriers (SLNs) are currently the most promising and novel lipophilic drug carriers. (10)


Nanohydrogels can be defined starting with the descriptions of macro-scaled hydrogels. Hydrogels are three-dimensional hydrophilic polymer chain networks that are crosslinked. These networks can consist of natural or synthetic polymers and display swelling behavior when introduced to water or physiological fluids. Moreover, they are able to revert to their initial state when removed from the presence of water/biological fluids. (11-13) Due to this unique behavior, hydrogels have gained attention and been adopted in biomedical applications such as drug delivery, drug release, and vaccine design. (14)

Drug delivery and drug release system designs that utilize hydrogels have been and are still considered appealing in medicine due to their crosslink-controlled pore structures. Moreover, physiochemically, hydrogels are very similar to the extracellular matrix of the human body. With also a very high content of water, hydrogels are known to have very high biocompatibility. A main disadvantage is their viscosity, which created an alternative solution: nanohydrogels. These submicron particles made excellent drug carriers that could easily be extruded through an injector needle. In addition, decreasing size ensures an increase in surface area that provides further bioconjugation. (11,15)

Nanogels, in the range of 10-100 nm size, are small enough to be used as systemic drug carriers. For designs that include clearance of nanogel carriers by kidney filtration the diameter is lower than 10 nm. Drug release to tissue, organs, or cells is through the meshes of nanohydrogels, which are typically between 5 and 100 nm in size. (16) Mesh sizes in environmentally dependent designs such as temperature- and pH-sensitive ones change with the stimuli according to the crosslink bond concentration that forms or breaks. (15) Regulating the breakages of crosslinking bonds that form the initial mesh size of the carriers will provide control of drug release acceleration. Other designs include utilization of the swelling capacity of nanohydrogels. (17) As swelling continues, mesh sizes increase and gradually release the encapsulated drug. (15)

Nanohydrogel carriers that are environmentally dependent include designs sensitive to pH, temperature, electric field, light, enzyme, calcium, glucose, redox, etc. (18) In this paper, some of these designs are summarized according to their sensitivity features as below. From this summary, it can be stated that as nanohydrogel carriers there are several popular materials that are prominent when compared with others. In Table 1, materials that receive the greatest attention from scientists are listed.

Temperature-sensitive nanohydrogel carriers

Temperature-sensitive nanohydrogel carriers are systems that exhibit swelling behavior that is dependent on temperature changes and are a widely studied field. (19) A temperature-sensitive drug-release design was reported by Ichikawa and Fukumori (20) in 1999. The design consists of a water-soluble hemostatic drug core inside a thermosensitive poly[N-isopropylacrylamide (NIPAAm)] nanohydrogel containing an ethyl cellulose shell. Ichikawa and Fukumori (20) stated that the mentioned shell could change and revert to its initial size with temperature changes between 30[degrees]C and 50[degrees]C in water and that nanohydrogels exhibit positive thermosensitive swelling. The drug release rate is reported to be not only temperature dependent but also nanohydrogel concentration dependent. (20) A very recent study introduced thermosensitive 5-fluorouracil (5-FU; a chemotherapeutic drug employed for solid tumor treatments) containing methyl cellulose (MC) nanohydrogels for decreased side effects of chemotherapy. In this 2018 study Dalwadi and Patel (21) produced MC nanohydrogels by a tip probesonicator method from MC hydrogels. 5-FU release depends on both temperature and its biodegradability. Within 48 h the drug is released in the injected area, preventing a cytotoxic drug burst in a very large area as in conventional chemotherapy. (21)

pH- and/or ionic-strength-sensitive nanohydrogel carriers

pH and/or ionic strength sensitivity allows nanocarriers' mesh size to be manipulated according to the environmental pH. Elsaeed et al. (22) synthesized poly(NIPA-co-AAC) nanohydrogels by inverse microemulsion polymerization method in 2010. On average, the diameter of these nanohydrogels is reported to range between 60 and 80 nm. The team delivers a possible drug release methodology that is pH dependent through poly (NIPA-co-AAC) nanohydrogel by characterizing its swelling behavior between the pH values of 4.00 and 8.00 (ionic strength=0.4). That study shows that the nanohydrogels' swelling capacity increased with environmental pH. (22) In an earlier study, in 2004, Dufresne et al. (23) reported pH-sensitive poly (N-isopropylacrylamide) derivative copolymers or poly(alkyl(meth)acrylate) diblock copolymers were produced as indomethacin (a nonsteroidal anti-inflammatory drug), fenofibrate (a drug for treating abnormal blood lipid levels), and doxorubicin (DOX) and aluminum chloride phthalocyanine carriers. PNIPAM copolymers were stated to be synthesized by free radical polymerization while the poly[alkyl(meth)acrylate] diblock copolymers were synthesized by atom transfer radical polymerization. The team carried out both in vitro and in vivo assays. Dufresne et al. (23) refer to the PNIPAM derivatives as a potential safe alternative to Cremophor[R]EL, a common carrier for various poorly water-soluble drugs. Furthermore, poly[alkyl(meth)acrylate] derivative [polyethylene glycol (PEG)-b-(EA-co-MAA)] nanoparticles were stated to be excellent carriers for hydrophobic drugs that could be used orally. The carrier system is reported to exhibit dissociation behavior with increasing pH. (23)


Chitin is a long-chain polymer derivative [poly (b-(1-4)-N-acetyl-D-glucosamine)] of glucose with significance as the raw material of CS nanocarriers (CSNs). When chitin is deacetylated up to about 50%, it transforms into CS, which has a linear backbone linked through glycosidic bonds. (24,25) CS's efficient bio-adhesiveness and permeabilization capacity make it one of the most popular nanocarrier materials amongst other hydrophilic polymers. (26) Moreover, CS is a nanocarrier that has a high loading efficiency of drugs. Based on the protonation of -N[H.sub.2] at the C-2 position of the D-glucosamine repeat, one of the most important characteristics of CS is its solubility in aqueous acidic media as given in Figure 1. (24) Thus, CS nanocapsules provide an effective solution for the delivery of hydrophobic drugs. (27) All the mentioned features of CS nanoparticles make it an excellent nanocarrier material.

Moreover, CS exhibits pH-sensitive behavior due to the percentage of its acetylated monomers and their distribution in the chains. (28) This behavior is utilized for controlled drug release by scientists. A common example for this is drug delivery to tumor cells and controlling release since the pH of tumor cells is significantly lower than that of healthy cells. (29) A summary of the literature that features CSNs as drug delivery systems is provided in Table 2 in chronological order. Production methods for CS carriers differ however, the most common method used being ionotropic gelation, which is based on the capability of polyelectrolytes to crosslink in the presence of counter ions. (30) As can be seen in Table 2, Fernandez-Urrusuno et al. (31) proposed the use of CS nanoparticles as potential drug carriers for transmucosal delivery in 1999. In their design the team loads insulin into CS nanoparticles to be given nasally to conscious normoglycemic rabbits. It is reported that there was a 40% reduction in the serum glucose levels. (31) Aktas et al. (34) reported the use of PEG-grafted CS nanoparticles as peptide drug carriers. They observed nanoparticle formation through intermolecular hydrogen bonding in an aqueous solution. The incorporation and release of insulin were dependent on the degree of introduction of the PEG chain on CS and observed sustained release phenomenon over time. (52,53) Perez-Alvarez et al. (51) reported one of the most recent studies in this field revealing the state of art in 2019. Their work exploits the designed CSN as a great candidate for polyoxometalate delivery into tumoral


Professor Andre Geim and Professor Kostya Novoselov made a groundbreaking disclosure by finally discovering a production method for GR in 2004. The research was outstanding since it had not been possible previously to produce a single layer of graphite (carbon atoms with sp2 bonds in the shape of honeycomb). Later, GR became known as the basic building block of graphitic materials such as spherical nanoparticles that are also known as 0D fullerenes, 1D carbon nanotubes, and 3D graphite. (54-58)

Following the discovery, scientists began to reveal GR's unique characteristics provided by its submicron dimension and the [pi]-conjugation in its structure. GR is revealed to exhibit extraordinary thermal, mechanical, and electrical properties. (57) Further research provided a better understanding of the physical and chemical structure of GR's surface, which has created interest in medical and pharmaceutical technologies as well as other fields of science. GR is researched and utilized for nanoscaffolds, chemical/biosensing, imaging, drug delivery and controlled drug release. (59) In the area of nanomedicine and nanocarriers, GR and its composites are important due to its large surface area where every single atom is exposed on the surface (2600 [m.sup.2] [g.sup.-1]), layer number, lateral dimension, surface chemistry, and purity. (60-62) Hereby, GR could be considered a superior candidate as an ideal nanocarrier with the mentioned characteristics that allows a high drug load capacity. (58)

One of the most popular derivatives of GR is GO, GR with oxygen-containing functionalities (epoxide, carbonyl, carboxyl, and hydroxyl groups). GR and GO have a major difference that affects their drug delivery performance when used as nanocarriers: GO is highly hydrophilic, whereas GR is hydrophobic so that it requires surface modifications for use in biological fluids. Thus, any nanocarrier design that uses GR should take into consideration the possible impurities and negative effects such as cytotoxicity. (61,63) This leads researchers to gravitate towards GO-containing designs rather than GR nanocarrier designs.

In Table 3, a summary of GR/GO nanocarrier designs is given. As can be seen, Hummer's method for production is the most popular choice, where graphite oxidative exfoliation is applied with NaN[O.sub.3]. Although Hummer's production method is usually opted for rather than other complicated methods, over the years it can be seen that nanocarrier designs have evolved into more complex systems that apply chemotherapy and photothermal therapy for treating cancer.

In 2008, Liu et al. (87) published a study that demonstrates PEG-functionalized GO nanocarriers used as a noncovalent physisorption chemotherapy drug delivery system. The team reveals that the nanocarriers have an adequate in vitro cellular uptake capacity. (87) A very recent study by Bullo et al. (88) examined the state of the art in GO nanocarriers. GO is reported to be synthesized by Hummer's method. GO is modified with PEG for higher biocompatibility and loaded with two chemotherapeutic drugs: protocatechuic acid and chlorogenic acid. The carrier is then coated with folic acid to target cancer cells since tumor surface membranes have a greater number of folate receptors. The final size of the nanocarrier system is stated to be 9-40 nm with a median of 8 nm. The team reveals that drug release of this design took more than 100 h, which ensures a steady therapeutic effect. (88)


Nanocarriers designed with a polymer foundation have a certain advantage in terms of the wealth of possible chemical modifications, including the synthesis of block and comb polymers. (89) Designs that use SLNs exploit this advantage by combining the advantages and avoiding the disadvantages of other colloidal carriers.

Lipids are defined as molecules that are hydrophobic or consisting of both hydrophilic and hydrophobic parts that are insoluble in water and soluble in organic solvents. (90) IUPAC gave the following further detailed definition in 1995:

"A loosely defined term for substances of biological origin that are soluble in nonpolar solvents. They consist of saponifiable lipids, such as glycerides (fats and oils) and phospholipids, as well as nonsaponifiable lipids, principally steroids." (9)

SLNs are developed by researchers as a substitute colloidal carrier with a spherical morphology for drug delivery and drug release. (5) SLNs have an average size of between 150 and 300 nm but could reach up to 1000 nm according to the surfactant used during production and are composed of roughly 0.1-30 (% w/w) solid fat. (92) Size and solid to liquid fat ratio affect the long-term stability, drug-loading capacity, and drug-release behavior of SLNs. (93) As mentioned, SLNs have several favored assets such as low to no toxic effect on healthy tissue and ease of production in greater units of production, ability to load both lipophilic and hydrophilic therapeutic agents, and high drug load capacity. (5) The most common use of SLNs as nanocarriers is for oral drug delivery. Other than this example, several drugs have been loaded using SLNs for drug delivery, such as doxorubicin and idarubicin, (94) thymopentin, (95) and camptothecin. (96)


Nanocarriers provide researchers with a highly applicable alternative method for targeted drug delivery and controlled drug release. The first and foremost reason that nanocarriers have become such a great focus in pharmaceutical technologies is that nanomaterials demonstrate extraordinary characteristics when compared with their larger scaled forms. These characteristics are summarized in this review as color, visible light, reactivity, surface area to volume ratio, conductivity, and surface tension. A variety of these carriers are more popular due to their high biocompatibility, ensuring greater efficacy especially in cancer treatments. Successful applications have not only ensured a greater focus on therapeutic development but also created a new solution available in the pharmaceutical market. In this paper, nanocarrier materials that have gained the most attention in drug delivery and release are summarized under the titles of nanohydrogels carriers, CSNs, GR and GO nanocarriers, and SLNs. Besides these nanomaterials there are also a great number of different nanocarrier designs that are not included in this review, such as gold nanocarriers, (97) starch and/or cellulose nanocarriers, (98) cerium oxide nanocarriers, (99) and carbon nanotube incorporated nanocarriers. (100) It is clear that, with further information gathered on nanocarriers for drug delivery and the current state in the development process of these nanomaterials, there is a high possibility to deliver better treatment to patients desperate in need of efficient treatment strategies.

Conflict of interest: No conflict of interest was declared by the authors.


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[iD] Sibel Aysil OZKAN (1*), [iD] Aylin DEDEOGLU (1), [iD] Nurgul KARADAS BAKIRHAN (2), [iD] Yalcin OZKAN (3)

(1) Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Turkey

(2) University of Health Sciences, Gulhane Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Turkey

(3) University of Health Sciences, Gulhane Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey

(*) Correspondence: E-mail:, Phone: +90 533 818 36 35 ORCID: orcid.org0000-0001-7494-3077

Received: 13.06.2019, Accepted: 01.08.2019

DOI: 10.4274/tjps.galenos.2019.48751
Table 2. A literature summary of CSNs

Date  Drug                Nanocarrier design
                          & advantages

1999  Insulin             Blood glucose control nasal absorption
                          pH selective release
2005  Epirubicin          Chemotherapy chitosan-bound magnetic
2005  BSA                 Carboxymethyl konjac glucomannan--chitosan
2005  Z-DEVD-FMK          Cerebral Ischemia Therapy CS-PEG-BIO-SA/OX26
2005  Insulin             Oral/Nasal Drug Carrier CS nanoparticles,
                          CS nanocapsules and CS-coated lipid
2006  Triclosan           Higher solubility in water hydroxypropyl
      Furoscmide          cyclodextrin containing chitosan nanocarrier
2006  Protein complex P1  Transmucosal drug carrier glucomannan-coated
                          chitosan nanoparticles
2006  Salmon calcitonin   Oral drug carrier carrier for peptide drugs
                          through the intestinal epithelium
2007  -                   Transmucosal drug carrier hydrophilic
                          cyclodextrin-chitosan core and chitosan
2008  Indomethacin        Ophthalmic Drug Delivery
2009  HP-b-CD complex     Oral delivery of drugs that are insoluble in
      simvastatin         water
2010  Bleomycin           Chemotherapy [Fe.sub.3][O.sub.4] containing
                          chitosan nanoparticles
2010  siRNA               PEGylated Chitosan Nanocarriers
                          Imidazole-modified chitosan-IAA nanoparticles
2010  Glutathione         Oral Drug Carrier Chitosan and Chitosan
                          /cyclodextrin NPs
2010  Mesalazine          Colon Specific Drug Delivery Superparamagnetic
                          chitosan-dextran sulfate NPs
2011  Silver NPs          Colon Cancer Apoptosis Chitosan-based
                          nanocarrier of silver NPs
2011  Curcumin            Hydrophobic drug delivery for cancer treatment
                          Carboxymethyl chitosan nanocarriers
2014  100% iron           Osteoarthritis treatment
2014  Rosmarinic acid     Antioxidant delivery
2015  Paclitaxel          Chitosan based glycolipid-like nanocarrier
2019  Polyoxometalates    Breast cancer therapy pH selective release

Date  Drug                CS nanoparticle production     Reference

1999  Insulin             Ionotropic gelation with        31
                          Pentasodium tri-polyphosphate
2005  Epirubicin          Carboxymethylated Chitosan      32
                          covalently bound onto
                          Fe3O4 nanoparticles
2005  BSA                 Dropping method                 33
2005  Z-DEVD-FMK          Chitosan acetylation 13.7%      34
2005  Insulin             Ionotropic gelation             35
2006  Triclosan           Ionotropic gelation             36
2006  Protein complex P1  Ionotropic gelation             37
2006  Salmon calcitonin   Ionotropic gelation             38
2007  -                   Ionotropic gelation             39
2008  Indomethacin        Ionotropic gelation by          40
                          addition of TPP anions
2009  HP-b-CD complex     Ionotropic gelation             41
      simvastatin         with Pentasodium
2010  Bleomycin           Ionotropic gelation             42
                          with Pentasodium
2010  siRNA               Complex coacervation of         43
                          nonmodified chitosan or
                          chitosan-IAA with siRNA
2010  Glutathione         Ionotropic gelation             44
2010  Mesalazine          Ionotropic gelation             45
2011  Silver NPs          Ionotropic gelation             46
                          with Pentasodium
2011  Curcumin            Ionic cross linking between     47
                          carboxyl group
2014  100% iron           -                               48
2014  Rosmarinic acid     Ionotropic gelation             49
                          with Pentasodium
2015  Paclitaxel                                          50
2019  Polyoxometalates    Crosslinked in inverse          51
                          microemulsion medium

CSN: Chitosan nanocarriers

Table 3. A literature summary of GR/GO nanocarriers

Date   Drug                       Nanocarrier

2010   Camptothecin (CPT)         FA-GONS-p-amino
       Doxorubicin (DOX)          benzenesulfonic acid
2011   Ellagic acid (EA)          GONS-Pluronic F38(F38), GONS - Tween
                                  80(T80), GONS-Maltodextrin (MD)
2011   Doxorubicin (DOX)          PEG-GONS
2011   Tamoxifen Citrate          Pyridinium bromide
       (TmC)                      (PY+-Chol)-Graphene (GR)
2013   Doxorubicin (DOX)          Polyethylene Glycol-Branched
                                  Polyethyleneimine-Reduced GO
2013   5-fluorouracil (5-FU)      Fe3O4-GONS
2013   Doxorubicin (DOX)          PVP-GONS-FA
2013   Doxorubicin (DOX)          FA-GONS-Chitosan (CHI)
2014   Doxorubicin (DOX)          GO/integrin aVb3 mono-antibody (Abs)
                                  /polyethyleneimine (PEI)/citraconic
                                  anhydride functionalized
                                  poly(allylamine) (PAH-Cit)
2014   Doxorubicin (DOX)          Hyaluronic acid (HA)-GONS
2014   Doxorubicin (DOX)          PEG-Poly (allylamine hydrochloride)
                                  (PAH)-2,3-dimethylmaleic anhydride
2015   Paclitaxel (PTX)           PEG-GO
2015   Irinotecan (IRI)           Poloxamer 188-GONS
       Doxorubicin (DI)
2015   Indomethacin (IMC)         poly(N-isopropylacrylamide)
       Doxorubicin (DOX)          (PNIPAM)-GO
2016   Doxorubicin (DOX)          Gold Nanoparticle (AuNP) - Folic
2018   Doxorubicin (DOX)          Folic acid (FA)-Graphene Oxide
       Camptothecin (CPT)         Nanosheet (GONS)
2018   Tetracycline (TC)          Carboxymethylcellulose(CMC)-Zn-Based
                                  Metal-Organic Framework (MOF-5)-GO
2018   Doxorubicin (DOX)          Carboxymethylcellulose (CMC)-Zn-Based
                                  Metal-Organic Framework (MOF-5)-GONS
2019   Quercetin (QSR)            Polyvinylpyrrolidone
       Gefitinib (GEF)            (PVP)-GO
2019   Cis                        Maghemitey-F[e.sub.2]
       -diamminedichloroplatinum  [O.sub.3]-GO
       (II) (CisPt)
2019   Methotrexate (MTX)         Polyethylene Glycol bis Amin
                                  (PEGA)- GO Magnetic NS (GOMNS)
2019   5-Fluorouracil (5-FU)      Chitosan-rGO
       Curcumin (CUR)
2019   Doxorubicin (DOX)          K-Carrageenan (K-Car)-GONS-biotin

Date   Nanocarrier design &          GR or go       Nanocarrier size
       advantages                    synthesis      on average

2010   Sulfonic acid groups          Hummer's       GONS (thickness)
       render stability in           method         < 150 nm
       physiological solutions
       Target: human breast
       cancer cells
2011   High drug loading (For        Hummer's       GONS-F38
       GO-T80, 1.22 g per 1 g)       method         (thickness)=6-7 nm
                                                    (thickness)=7-8 nm
                                                    (thickness) =5-6 nm
2011   Both chemotherapy             Hummer's
       and near infrared (NIR)       method
       photothermal therapy
       Lower systematic
2011   Enhanced the apoptosis        -              PY+-Chol-GR
       of cancer cells                              (hydrodynamic
                                                    diameter)=150-200 nm
2013   Photothermally                Reduction      100-200 nm
       controlled anti-cancer        by hydrazine
       drug delivery                 monohydrate
       Higher cancer cell death

2013   pH dependent                  Hummer's
       chemotherapy                  method
       High drug loading
       capacity of up to 0.35
       mg [mg.sup.-1]
2013   pH sensitive nanocarrier      Hummer's       GONS=100 nm
       Both chemotherapy             method
       and near infrared (NIR)
       photothermal therapy
2013   High drug loading             Hummer's
       efficiency (0.98 mg/mg)       method
       & prolonged drug release
       pH sensitive drug release
2014   Charge-reversal, target       Hummer's       GO/PEI/PAH-Cit
       specific nanocarrier          method         /DOX=20-200 nm
       Drug release in acidic
       intracellular organelles
2014   Targeted and pH               Hummer's       GONS
       sensitive drug delivery       method         (lateral)=10-200
       High loading efficiency                      nm
       of drug (42.9%)
2014   pH sensitive drug             Hummer's       PEG-PAH-DA
       release                       method         -GONS=70 nm
       Both chemotherapy and
       photothermal therapy
2015   Nontoxic chemotherapy         Hummer's       PEG-GO-PTX
       carrier                       method         (lateral)=50-200
       Increased biocompatibility                   nm
       and physiological stability
2015   Photothermal                  Hummer's       GONS=200 nm
       therapy with dual             method
       chemotherapies in one
2015   Enhanced thermal              Hummer's       GONS=0.85 nm
       stability                     method         NIPAM-GONS=3.2
       Improved dispersibility in                   nm
       aqueous and cell medium
2016   Targeted chemotherapy                        AuNP-FA-GONS
       and photothermal                             (Hydrodynamic
       ablation                                     size)=188.2[+ or -]
                                                    7.2 nm AuNP-GO
                                                    (diagonal)=135 nm
2018   FA linked GONS for high       Hummer's       2.7 nm
       affinity to                   method
       folate receptor
2018   Efficient oral drug           Hummer's       CMC/MOF-5/GO
       delivery                      method         (diameter)=344 nm
       Effective protection
       against stomach pH
2018   Targeted delivery and         Hummer's       GONS
       controlled release of         method         (Thickness)=30 nm
       chemotherapy human                           CMC/MOF-5
       blood cancer cell lines                      /GONS=80 nm
2019   High biocompatibility         Hummer's       GO=166.5 nm
       Enhanced anticancer           method         PVP-GO=300-400
       activity within a dosage                     nm
2019   Efficient Malignant           Hummer's       GO (width)=80-100
       glioma chemotherapy           method         nm
       GONP accumulates in                          GO (thickness)=6.3
       U87 human glioblastoma                       nm
       subcutaneous tumor
2019   Magnetic Iron NPs             Hummer's
       Increased efficacy in         method
       chemotherapy with pH
       dependent drug release
       and biocompatibility
2019   Increased efficiency of       -              -
       chemotherapy against
       colon cancer
2019   Targeted therapy for          Hummer's       x-Car-GONS-biotin
       cervical cancer               method         (thickness)=219 nm
       pH-sensitive drug release

Date   Reference

2010   64
2011   65
2011   66
2011   67
2013   68
2013   69
2013   70
2013   71
2014   72
2014   73
2014   74
2015   75
2015   76
2015   77
2016   78
2018   79
2018   80
2018   81
2019   82
2019   83
2019   84
2019   85
2019   86
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Author:Ozkan, Sibel Aysil; Dedeoglu, Aylin; Bakirhan, Nurgul Karadas; Ozkan, Yalcin
Publication:Turkish Journal of Pharmaceutical Sciences
Date:Dec 1, 2019
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