In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery

, S. TAMIZHARASI, T. SIVAKUMAR Nandha College of Pharmacy and Research Institute, Erode 630052, Tamilnadu, IndiaEmail: sumoraji@gmail.comObjective: The objective of this study was to formulate and evaluate the poorly soluble drug, naringenin (NAR) into nanosuspension to increase the solubility and enhance the dissolution rate and then improve its bioavailability.Methods: Nanosuspenion of naringenin (NARNS) was prepared using high-pressure homogenization method using Soya lecithin, Polaxamer-407, Polaxamer-188, Hydroxypropyl methyl cellulose (HPMC) and Tween-80. Ten formulations were prepared to show the effect of stabilizer and its ratio. D-α-Tocopheryl polyethene glycol succinate 1000 (TPGS) was added as a co-stabilizer. All these formulations were evaluated for their particle size, PDI, zeta potential, FT-IR study, drug content, saturation solubility studies, entrapment efficiency, in vitro permeability and in vitro drug release. The formulation was further evaluated for scanning electron microscope (SEM), differential scanning calorimetry (DSC) and Powder X-ray diffraction (P-XRD) and hemocompatibility assessment.Results: All the prepared formulations were in the nano size. The optimum concentration of the stabilizer was in the formulation was found 1:1.5:1 (drug: stabilizer: co-stabilizer ratio). Dramatic effect of the particle size reduction was found by the addition of the co-stabilizer (TPGS) in formulation N2 that has P. S 80.52±0.13 nm. The solubility and dissolution of NAR in the form of NARNS were significantly higher than those of pure NAR. SEM report shows that naringenin nanosuspension revealed a smooth texture. P-XRD crystallography diffraction and DSC studies indicated that the crystalline state of NAR was converted into amorphous nature. The safety evaluation showed that NARNS provided a lower rate of erythrocyte hemolysis.Keywords: Naringenin, High-Pressure Homogenization, Nanosuspenion, Solubility, Bioavailability Conclusion:In this study, (NARNS) was successfully carried out by high-pressure homogenization technique and characterized. The physiochemical characterization shown that crystalline naringenin was converted to a polymorphic form (DSC and P-XRD Study) which evidenced by enhanced dissolution rate in comparisons of the formulation with (NAR) pure drug. The NARNS has shown 7.5±0.4 fold increased relative bioavailability when compared to the NAR. The increased drug dissolution rate may have a significant impact in absorption which in turn the improved oral bioavailability of naringenin. Thus, this delivery system may prefer to improve the dissolution of poorly soluble drugs like NAR and thus enhanced oral bioavailability. The safety evaluation showed that nanoformulation (NF2) shows a lower rate of erythrocyte hemolysis. These findings suggest that the selected formulation may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.

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“…These distinctive bands of free NAR are also present in NARNS, which indicates the chemical stability of NAR in nanosuspensions [42,43].…”

Section: Fourier Transforms Infrared Spectroscopy (Ft-ir)mentioning

confidence: 87%

Formulation and Evaluation of Polymeric Nanosuspension of Naringenin

Sumathi¹,

Sengodan²,

Sivakumar³

2017

Int J App Pharm

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“…33 Despite the successes recorded following noncovalent method of conjugation of FA to other biomolecules or MNPs, [29][30][31][32][33][34] several work reported a superior performance following covalent methods of interactions. 4,35,36 However, the greatest challenge is meeting the requirements of specific conjugation chemistry that retains QDs biochemical activity as much as possible. Despite the superiority of covalent coupling of FA to QDs by means of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-based chemistry, some researchers reported that 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide has short half-life in water and results in poor coupling efficiency.…”

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confidence: 99%

Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

Bwatanglang¹,

Mohammad²,

Yusof³

et al. 2016

IJN

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In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn 2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging.

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“…Targeted delivery of drugs through covalent binding of carboxymethylchitosan nanoparticles and folic acid was recently found to be possible. It was assumed that the latter would assist penetration of the nanoparticle into the cell and cause its apoptosis [4].The present communication reports the synthesis of the conjugate of a bisphosphonate derivative and folic acid. A one-step synthesis using the structural synthetic building block 1-(2-aminoethylamino)-1-(diethylphosphoryl)ethylphosphonic acid diethyl ester (2) (4) was 20%.…”

mentioning

confidence: 90%

mentioning

confidence: 99%

Synthesis of a bisphosphonate derivative of folic acid

2013

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547.859.1 1-Amino-1,1-bisphosphonates are attracting heightened attention in various sectors of chemistry and medicine owing to a combination of unique chemical, physical, and biological properties. The combination of these properties opens possibilities for molecular design and synthesis of various biologically active compounds that are used as immunomodulators, calciumexchange regulators, and antitumor drugs [1]. Complex conjugates of bisphosphonates and natural biologically active compounds have recently become interesting. Thus, bisphosphonates based on widely known antibiotics of the fluoroquinolone series [2] and the folic-acid antagonist methotrexate, which is used to treat neoplastic diseases [3], were synthesized. Targeted delivery of drugs through covalent binding of carboxymethylchitosan nanoparticles and folic acid was recently found to be possible. It was assumed that the latter would assist penetration of the nanoparticle into the cell and cause its apoptosis [4].The present communication reports the synthesis of the conjugate of a bisphosphonate derivative and folic acid. A one-step synthesis using the structural synthetic building block 1-(2-aminoethylamino)-1-(diethylphosphoryl)ethylphosphonic acid diethyl ester (2) (4) was 20%. The structure of the product was confirmed using PMR and 31 P NMR spectroscopy and mass spectrometry. Thus, the first bisphosphonate derivative of folic acid was synthesized. REFERENCES 1.V. D.

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In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery

Cited by 118 publications

References 34 publications

Formulation and Evaluation of Polymeric Nanosuspension of Naringenin

Formulation and Evaluation of Polymeric Nanosuspension of Naringenin

Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

Synthesis of a bisphosphonate derivative of folic acid

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