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Chitosan [poly (1ĺ4)-2-amino-2-deoxy-ȕ-D-glucan] is a cationic polysaccharide
made by alkaline N-deacetylation of chitin and shows good biocompatibility and
biodegradability. Major limitation with the use of chitosan is its poor water- þ






solubility. Hence, water-soluble derivatives of chitosan are garnering attention


recently. Also, chitosan derivatives have demonstrated unique biological activities

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including antitumor, antiulcer, immuno-stimulatory, and antibacterial. One such


promising candidate is succinyl chitosan (Suc-Chi). Actinic keratosis (AK) is a UV





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thymidylate synthetase. Several formulations of 5-FU are available, including a 5%

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Formation of Suc-Chi was confirmed by IR in the range of 410-425nmJK







 

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The synergistic effect on cell toxicity seen foresees that such kind of gel
1. Synthesis and optimization of synthetic route for Suc-Chi from chitosan. formulation for the topical application of cytotoxic drug can be develop
2. Determination of physicochemical parameters of Suc-Chi. successfully.
3. Cell toxicity study of Suc-Chi and 5-FU.
4. Development of Suc-Chi based topical drug delivery.
5. Performance evaluation of the developed product.

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Chitosan in aqueous acetic acid was reacted with succinic anhydride for 24 hrs at
400C. Reaction mixture was cooled to room temperature, and precipitated in excess
of acetone and dried.
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 Suc-Chi was characterized by FTIR in the range
of 400-4000 cm-1, DSC from 75- 400°C under continuous flow of dry nitrogen gas
(50 ml/ min) at heating rate of 20°C/ min. and by NMR spectroscopy.
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"" # $ $ antitumor activity of Suc-Chi and 5-FU Cell toxicity
study and was ascertained on normal fibroblast cell and SK-MEL-2 cell line.
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To 10 ml of 0.02% nanosilver solution, 100 mg of carbopol 940 was added to get
1% aqueous carbopol gel loaded with nanosilver. Polyethylene glycol was used as



humectants in the concentration of 5% w/v. required viscosity was built by drop
wise addition of 10%v/v triethnolamine solution. The resulting gel was sonicated The evaluation of formulated gel against AK using specific cell line was the
for 30 minutes to assure the uniform distribution of nanosilver through the gel. major objective of the present study. Cytotoxic activity of prepared 5-FU topical
gel was evaluated against SK-MEL-2 cell line. Our findings suggest that the
developed topical gel formulation of 5-FU with Suc-Chi demonstrates synergistic
cytotoxic effect on the cancerous cells with a reduction in dose. Also the study
can be extended to other types of cell lines.
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Chitosan [poly (1ĺ4)-2-amino-2-deoxy-ȕ-D-glucan] is a cationic polysaccharide evaluated for consistency, clarity, pH, spreadability, viscosity, drug content, and in
made by alkaline N-deacetylation of chitin and shows good biocompatibility and vitro drug release (Keshary-Chein diffusion cell using cellophane membrane).
biodegradability. Major limitation with the use of chitosan is its poor water-
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solubility. Hence, water-soluble derivatives of chitosan are garnering attention


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recently. Also, chitosan derivatives have demonstrated unique biological activities



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including antitumor, antiulcer, immuno-stimulatory, and antibacterial. One such





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promising candidate is succinyl chitosan (Suc-Chi). Actinic keratosis (AK) is a UV





light-induced lesion of the skin that may progress to invasive squamous cell


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carcinoma. 5-Flurouracil (5-FU) is one of the most frequently used drugs for the

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treatment of AK as it causes cell death in actively proliferating cells by inhibiting





thymidylate synthetase. Several formulations of 5-FU are available, including a 5%


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cream or solution, a 2% solution, a 1% cream or solution, and, most recently, a





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micronized 0.5% cream.

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Øéê»ËÂȼ»Ð Formation of Suc-Chi was confirmed by IR in the range of 410-425nm,

1. Combine anticancer and penetration enhancing activities of Suc-Chi with 5-FU
activity and reduce the dose of drug required during formulation.
2. To evaluate the formulated gel against AK using SK-MEL-2 cell line and ascertain
69  ** 6 3:-**&5
the cytotoxic activity of prepared 5-FU topical gel against the same. 1 H1* 2.366
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1. Synthesis and optimization of synthetic route for Suc-Chi from chitosan.
2. Determination of physicochemical parameters of Suc-Chi.
3. Cell toxicity study of Suc-Chi and 5-FU.       <       < 
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The synergistic effect on cell
400-4000 cm-1, DSC from 75- 400°C under continuous flow of dry nitrogen gas (50
ml/ min) at heating rate of 20°C/ min. and by NMR spectroscopy. toxicity seen foresees that
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study was performed on normal fibroblast cell and SK-MEL-2 cell line. for the topical application of
% &""' (" cytotoxic drug can be
To 10 ml of 0.02% nanosilver solution, 100 mg of carbopol 940 was added to get 1% develop successfully.
aqueous carbopol gel loaded with nanosilver. Polyethylene glycol was used as
humectant at a concentration of 5% w/v. Viscosity was built by drop wise addition of
10%v/v triethanolamine solution. The resulting gel was sonicated for 30 minutes to
assure uniform distribution of nanosilver throughout the gel. '"$'"*$&"From the evaluation of all the developed
formulations 8was found to be smooth, transparent with good spreadibility,
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F4 0.5 1 15 20 63.5 formulation for the topical application of cytotoxic drug can be develop
F5 0.5 1 20 5 73.5 successfully.
F6 0.5 1 20 10 68.5
F7 0.5 1 20 15 63.5

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F8 0.5 1 20 20 58.5 The authors are thankful to ICPA and K-LAB for their generous support
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