2023.08.03.134

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Loading Cephalexin on Chitosan Polymer and using the drug's Natural polymer for Medical use.

Raisan Kadhim Taresh^1,*, Firyal Mohammed Ali²

¹ Sumer University, College of Science, Department of Pathological Analysis

² Al-Mustansiriyah University ; College of Science ; Department of Chemistry

* Correspondence: raisankadim @gmail.com . https://orcid.org/0000-0003-2978-7575, [email protected].

Available from. http://dx.doi.org/10.21931/RB/2023.08.03.135

ABSTRACT

The modification of natural polymers, such as Chitosan (CH), is of interest in this research because it preserves the critical structure of the (CH) skeleton while introducing new or enhanced features. The polymer was made by changing the structure of (CH) with a vinyl monomer like acrylic acid (CH-g- Itaconic acid). The graft copolymer was alleviated with Cephalexin (CE) through the amino group, using a free radical initiator, ceric ammonium nitrate. Because of the digestive nature of this work, it necessitates a long-term controlled delivery (CD). The synthesized copolymer was submitted to a variety of analytical approaches, including (FTIR), (UV), and (1H-NMR) spectroscopy, as well as thermal studies like TGA and DSC. The produced polymer's physical characteristics were examined. Our findings reveal that in an in vitro investigation, sustained release (SR) was examined at 37 °C, and drug release (DR) was compared over a few days. The hydrolysis rate in the primary medium was more significant than in the acid medium. Sustained release (SR) was talented for people afflicted with bacteria and wounds after multiple compensations of continued release by a modified medication and in vivo presentation.

Keywords: Chitosan; acrylic acid; Graft Drug Copolymer.

INTRODUCTION

Natural derivative polymers ¹are widely employed in the pharmaceutical and biomedical industries for various applications (DR). Many polymers have been heavily changed to control controlled release (CR)^2,3. The production operated as a delivery service, with numerous compensations comparable to synthetic polymers, and it was available^4,5. Polymers linked with pharmaceuticals usually have a half-life, which reduces medication bioavailability by lowering solubility, stability, and immunogenicity⁶. Allowing for targeting and DR and reducing adverse effects⁷, Many drug delivery systems can be built to provide various medications and release them regulated to improve therapeutic efficacy 8. Grafting is an effective way to give a polymer diverse groups. Graft polymers are also known as graft copolymers because they comprise at least two different types of monomer units for polymer modification ^9,10, partially deacetylated (DA) polymer of (CH), and are typically prepared from chitin using a robust alkaline solution. Chitosan was made by deacetylating chitin to greater than 60%. (CH) possesses several features that have attracted attention, including biodegradability, biocompatibility, and nontoxicity. There is an amine group in CH. ^11,12 when a cross-linker is present. The influence of reaction factors like monomer ratio was investigated¹³. Cephalexin (CH) is an antibiotic with a high bacterial confrontation level ¹⁴. (CH) is a biocompatible, nontoxic, biodegradable substance. Because (CH) is not widely distributed, it must be taken from natural resources. It is made mainly by eliminating acetyl groups¹⁵.

The aim of this work includes the synthesis of new natural drug polymers by using natural polymers as carrier polymers attached to different drugs and modification of biological polymers to give new or improved and to develop various properties.

Figure 1. Chemical structure of chitin and Chitosan.

To enhance the quality of drug delivery to controlled release and improve drug therapy. It is critical to comprehend and comprehend the mechanics of molecules, particularly the release system. Only a diverse set of connections between the drug and the polymer backbone may produce this polymeric prodrug ¹⁵.

MATERIALS AND METHODS

(CH) powder has a molecular weight of 100,000 Dalton (Japan) and contains analytical-grade Dioxin and acetic acid without further processing. Sigma provided Ceric Ammonium Nitrate (CAN), Itaconic acid (A), and Cephalexin; all chemicals and reagents were utilized without purification.

Instrumentation

The melting point was determined by utilizing (Kofler- method). Shimadzu 8400 FT-IR photometer for infrared spectra; Bruker spectrophotometer for 1H-NMR spectra. NET Z U. (UV-Vis)- spectrum photometer type VARIAN was used to obtain a DSC thermogram.

Preparation Of Ch-G-I (Chi) ¹⁶.

Drop by drop, 1 gram of (CH) was dissolved in (5) mL of (10%) acetic acid. (1mL) of (CAN) (1gm) of Itaconic acid was added to a polymerization flask and heated for (40) minutes in an inert environment (55C0). The polymer product had a conversion ratio of (50.5) percent and a melting point of (144–203C0). Thionyl chloride was used to convert the carboxylic group to the equivalent of an acid chloride.

Substitution Of(Chi) With Cephalexinch-G-Ich(Ch-G-Ich)¹⁷

(CHI) (0.94 gm) was dispersed in (4 mL) of Dioxin; (0.94 gm. 0.0017mol) of Cephalexin was dissolved in (4 mL) of Dioxin; (0.5 mL) (DMF) was added to the mixture, then heated with stirring for 1 hour at (55 C0); the colored solution was filtered and the filtrate was isolated, then the solvent was evaporated, giving a new dark yellow product (CH Percentage conversion rate (82 percent ). The table included a list of all physical attributes (1).

Table 1. Includes a list of all physical attributes.

Drug Release Of (Ch-G-Ic) ^16,18

The (CH-g-Ich) release was investigated. 0.1 gram was added to a buffer solution (100 ml) at room temperature (37 0C). Using a UV spectrometer, we measured pH (1.1–7.4). UV-spectroscopes were used to record the sustained release regularly. The max wavelength was measured various times, and the mole fraction created was calculated from the UV spectra.

RESULTS

Graft copolymerization was employed in this study. Itaconic acid, having a (CH) backbone [16], acquired new characteristics and was used in medication development. With improved solubility and amine group modification, The chemical change did not alter the critical skeleton of (CH), preserving the distinctive features and introducing new or enhanced ones. Its chemical characteristics were chosen with care. The polymer was made by grafting Chitosan with the amino group of Cephalexin and then modifying the (CH) structure with Itaconic acid CH-g- Itaconic acid using ceric ammonium nitrate as an initiator.

Synthesis (CH-g-AA)

Drug-NH2 = Cephalexin Drug-NH2 = Cephalexin

Figure 2. Scheme 1. of Synthesis (CH-g-AA)

Figure 3. FTIR spectrum copolymer(CH-g-I)

Figure 4. ¹H-NMR Spectrum of polymer (CH-g-I)

Figure 5. FTIR Spectrum of Copolymer Chitosan-g-[N-Cephalexin itaconic acid]

Figure 6. ¹H-NMR Spectrum of Copolymer (CH-g-ICE)

Figure 7. UV Spectrum of (CH-g-ICE) in Acid Medium

Figure 8. UV Spectrum of (CH-g-ICE) in base medium

Figure 9. UV Spectra of hydrolysis of (CH-g-Ach) in pH 7.4 and pH 1.1

Figure 10. TGA Spectrum of (CH-g-ICE)

DISCUSSION

Identification of the FT-IR Spectra, Figure (1) Some peaks of (CH) are seen at 3445 cm-1 (O-H as stretch); 2850 cm-1 (C-H as stretch); 1650 cm-1 (N-H as bend); and 1034 cm-1 (C-O as stretch) in FTIR Figure 1. In the spectrum of CH, some new absorption peaks at 1740, 1537, 1450, and 1392 cm-1 are -CO, -COO; -CH group, -COO accordingly, in addition to the CH identifying peaks. These findings revealed that acrylic acid had grafted onto the (CH) structure of the polymer. At 3450 cm1, several bands were identified that were attributable to the amine group (–NH2). Moreover, intermolecular hydrogen bonding is responsible for a wide range (3000–3450) cm1. The stretching vibration of the C–N group has a peak at 1624 cm1, and the OH stretching of the alcohol group has an adsorption band at 3360 cm1. Also Figure 3 FTIR spectrum of copolymer Chitosan-g-[N-Cephalexin itaconic acid] shows the appearance absorption of (3225 cm-1) of ʋ(O-H) group and (2829-2928 cm-1) due to ʋ(C-H aliphatic) and (1714,1770 cm-1) due to ʋ(C=O) carboxylic and another absorption peaks at (1647,1662 cm-1) of ʋ(C=O) amide. Proton nuclear magnetic resonance (¹H-NMR), figure (2) shows the 1H-NMR spectrum of prepared polymer Chitosan-g- itaconic acid(CH-g-I), which showed the following signals. 2 ppm (doublet, 2H, CH2-CH) for Chitosan, 2.5 ppm (doublet, 1H, CH-CH) for itaconic acid, 4.5 ppm (Singlet, 1H, CH2-OH), 5.5 ppm (Singlet, 1H, CH-OH) for Chitosan, 7.5 ppm (Singlet, 1H, NH), 11.9 ppm (Singlet, 1H, COOH). Figure 4 The 1H-NMR spectrum of prepared polymer Chitosan –g-[N-Cephalexin itaconic acid] (CH-g-IC) showed the following signals. Ppm (doublet, 2H, CH2-CH), 2.5 ppm (Triplet, 1H, CH-C2H2) for Chitosan, 4-4.5 ppm (Singlet, 1H, OH), 6 ppm (Multiple, 5H, Aromatic), 7.5 ppm (Singlet, 1H, CO-NH amide). In the study of Controlled Release CR of Chitosan –g-[N-Cephalexin itaconic acid]¹⁹, the release of (CH-g-IC) was investigated by continuously adding 0.1 gm in a buffer solution (100 ml) at 37 0C. At pH (1.1 and 7.4), the max wavelength was observed. As shown in Figure 5, the samples were inspected using a UV spectroscope, and the mole fractions were calculated using UV spectra. The spectrum of (CH-g-IC), The thermal study of (CH-g-I) and (CH-g-IC) (Figure.8) revealed an exothermic peak for (CHI) and (CH-g-IC) at 90°C and 100°C, respectively. Water retention could explain the difference in endothermic peaks. Exothermic maxima for (CH-g-I) and (CH-g-IC) were seen at 300 and 450 degrees Celsius, which could be linked to the amide groups. At 40 and 100°C, TGA of CH reveals a weight loss of roughly 65 percent. This could be due to a lack of water. Another stage of weight loss is at 290°C and bears to 500°C, when there was a 55 percent weight loss due to the filth of CH... TGA Spectrum of (CH-g-IC) (Figure.8). shows the stages of weight loss that occur between 30°C and 470°C. At 45°C and up to 298°C, there was a 10% weight loss owing to water loss, and from 290°C to 455°C, the (CH-g-IC) had a lower weight loss of 26% than pure (CH). These changes increase the (CH-G-IC) (CHI) thermal stability.

CONCLUSIONS

The results demonstrate that (CHI) was transformed with a drug with a slow-release performance that was known to be talented when employing natural polymer as a drug carrier. It was determined that the rate of hydrolysis is pH 7.4 higher than pH 1.1; it was believed that (CH-g-IC) release with extended drug activity via gradual release was compared at the start and after three days.

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Received: 25 June 2023/ Accepted: 26 August 2023 / Published:15 September 2023

Citation: Taresh , R.K.; Ali , F.M. Loading Cephalexin on Chitosan Polymer and using drug Natural polymer for Medical use. Revis Bionatura 2023;8 (3) 135 http://dx.doi.org/10.21931/RB/2023.08.03.135