Conference Proceeding

Mathematics in Space and Applied Sciences (ICMSAS-2023)
ICMSAS-2023

Subject Area: Mathematics
Pages: 331
Published On: 03-Mar-2023
Online Since: 04-Mar-2023

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 Book Chapter

Oxidized-Cellulose for pH-triggered in vitro Doxorubicin Release

Author(s): Sapana Kumari

Email(s): naddasapana@gmail.com

Address: Dr. Sapana Kumari
Department of Chemistry, NSCBM Govt. Degree College Hamirpur, H.P., India-177005
*Corresponding Author

Published In:   Conference Proceeding, Mathematics in Space and Applied Sciences (ICMSAS-2023)

Year of Publication:  March, 2023

Online since:  March 04, 2023

DOI:


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Oxidized-Cellulose for pH-triggered in vitro Doxorubicin Release

 

Dr. Sapana Kumari

Department of Chemistry, NSCBM Govt. Degree College Hamirpur, H.P., India-177005

*Corresponding Author E-mail: naddasapana@gmail.com

 

ABSTRACT:

The foremost requisite for chemotherapy is site specific drug delivery so as to avoid various associated side effects. To achieve this, stimuli-responsiveness of the support material is of great interest to selectively release the loaded drug to tumor cells. Therefore, in the present study, cellulose was modified by oxidization with sodium periodate (NaIO4) to dialdehyde cellulose (DAC). The synthesized DAC was applied as support material for doxorubicin (Dox), as model anticancer drug. The drug was loaded on this support material via pH-responsive linkages between functional groups of Dox and DAC. The release behaviour of Dox was studied in the different pH medium. Dox release was observed to be maximum at pH 5.0 and pH 6.8 i.e., endosomal and extracellular pH, respectively in tumor tissue, and minimum at physiological pH 7.4 of normal tissues. Various mathematical models were applied to elucidate the release mechanism of Dox from the loaded DAC and showed non-Fickian diffusion mechanism. The results suggested that this pH-responsive DAC support material is effective and promising Dox-delivery carriers for cancer treatment and capable of reducing side-effects of this anticancer drug to the normal cells.

 

KEYWORDS: Cellulose, oxidation, doxorubicin, drug loading, drug release mechanism.

 

1. INTRODUCTION:

The major goal in cancer treatment is the controlled drug delivery at target sites and to avoid the adverse effects on other tissues [1]. However, dose−dependent cardio-toxicity is exhibited by anticancer drugs which may lead to heart failure due to the lack of ability to target cancer cells [2]. In order to overcome this limitation, stimuli−responsive carriers, have been exploited for site−specific delivery of drugs. The one of the major challenges to achieve this site specific effect is to discover a suitable drug carrier with high drug loading capacity, stability, long circulation times in the bloodstream, the ability to target cancer cells, and the ability to efficiently deliver and release drugs at the target site [3]. Stimuli−responsive and site−specific release of the drug can be accomplished by stimuli such as pH, glucose and magnetic field [4,5]. Among these stimuli, pH variation in tumor tissue is an ideal trigger due to the fact that the pH at tumor site is lower than the pH of normal tissue. The extracellular pH value in tumor tissue is acidic (pH 6.8), and even more acidic in intracellular compartments such as endosomes and lysosomes (5.0-6.5), in comparison to the physiological pH (7.4) of normal cells [4]. So various pH responsive materials have been developed to efficiently for the site specific delivery of anticancer drug doxorubicin (Dox) [6-13]. Such pH responsive carriers can be developed by inserting acid-labile linkers between drug and carrier that undergo destabilization in tumor environment and release of drugs into cancer cells. One of such acid-labile linker is imine bond (-C=N-) which has been employed as pH-responsive linkage for anticancer drug conjugation to allow drug release in acidic cancerous media [14-16]. Zhao et al. have conjugated Dox to magnetic nanoparticles via imine linkage and an enhanced release of Dox was observed at pH 5.4 with relative stability at pH 7.4 [15]. Basuki et al. synthesized iron oxide nanoparticles with grafted polymer shells having aldehyde functionality to enable the reversible attachment of Dox via imine bonds for controlled release of Dox in acidic tumor environment [16]. Such pH responsive imine linkages can be inserted in drug delivery systems via conjugation of NH2 groups of Dox and aldehyde groups of carrier.

In view of the above discussion, in the present work, oxidation of cellulose extracted from pine needles was carried out with sodium periodate (NaIO4) to get the required aldehyde functional groups for pH responsive linkages required for pH triggered release at target site. Cellulose is the most abundant, low cost and nontoxic biopolymer in nature and its derivatives find applications in diverse fields including in drug delivery devices [17-21]. There are some reports in literature in which oxidized cellulose has been used as potential drug delivery devices [22-25]. Volkert et al. have reported 2,3-dialdehyde cellulose as carrier for drugs like benzocaine and prazosin [24]. Hence, in the present study we have applied the oxidized cellulose having aldehyde functional groups, for delivery of doxorubicin (Dox), as model anticancer drug via pH responsive imine linkages.

 

2. EXPERIMENTAL SECTION:

2.1 Materials.  NaIO4, doxorubicin hydrochloride (Dox, Samarth Life Sciences Pvt. Ltd. Himachal Pradesh, India), di-sodium hydrogen orthophosphate anhydrous (Na2HPO4), sodium dihydrogen orthophosphate dihydrate (NaH2PO4.2H2O, S.D Fine-Chemicals Ltd.), NaOH, HCl, all were of analytical grade and used as received. The double distilled water was used in all the experiments.

2.2 Synthesis of Oxidised Cellulose. Cellulose extracted from pine needles was oxidized at C2-C3 position using NaIO4 (1.65 g) at room temperature for 72 h in dark condition [17,18]. The remaining NaIO4 was neutralized with an excess of ethylene glycol. The oxidized cellulose was filtered and thoroughly washed with water.

2.3 Characterization Techniques. Fourier transform infrared (FT-IR) spectra were recorded on a Perkin Elmer FT-IR spectrophotometer between 4000 and 400 cm-1 using KBr discs. Powder X-ray diffraction (XRD) measurements were carried out with Philips PAN Analytical XPERT-PRO X-ray diffractometer using a wavelength of 1.54060 Å (Cu-Kα radiation) with diffraction angle 2θ varied from 10 to 70º.

2.4 Dox Loading and Release Experiments. A known weight of DAC was immersed in Dox solutions (0.25 mg/mL) prepared in phosphate buffer saline (pH 7.4) at 37 °C for 72 h. After specific time intervals, the absorbance of the solution containing the residual drug was measured on UV-Vis spectrophotometer (Photolab 6600) at 498 nm and the amount of loaded drug was calculated from a calibration curve prepared for the drug. After the optimum drug loading, the Dox-loaded DAC (DAC-Dox) was filtered and washed with the distilled water to remove any free drug on the surface and dried at room temperature. The % drug uptake (Pu) by DAC was calculated as given below:



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Dr. Sanjay Kango

Department of Mathematics, Neta Ji Subhash Chander Bose Memorial, Government Post Graduate College, Hamirpur Himachal Pradesh-177 005, INDIA




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