2023.08.03.134
Files > Volume 8 > Vol 8 No 3 2023 > Diyala 3
Loading Cephalexin on Chitosan Polymer and using the drug's Natural polymer for Medical use.
Raisan Kadhim Taresh1,*,
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 1 are 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 available4,5. 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 effects 7, 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.
REFERENCES
1.
Rinaudo,
M., Chitin and chitosan: Properties and applications. Progress in polymer
science, 2006. 31(7): p. 603-632.
2.
Zhang, J.-F.
and X. Sun, Mechanical properties of poly (lactic acid)/starch composites
compatibilized by maleic anhydride. Biomacromolecules,
2004. 5(4): p.
1446-1451.
3.
Vårum, K.M., et
al., In vitro degradation rates of
partially N-acetylated chitosans in human serum. Carbohydrate research, 1997. 299(1-2): p. 99-101.
4.
VandeVord,
P.J., et al., Evaluation of the
biocompatibility of a chitosan scaffold in mice. Journal of Biomedical
Materials Research: An Official Journal of The Society for Biomaterials, The
Japanese Society for Biomaterials, and The Australian Society for Biomaterials
and the Korean Society for Biomaterials, 2002. 59(3): p. 585-590.
5.
S. M.
Abdulateef, O. K. Atalla1, M. Q. A L-Ani, TH. T Mohammed, F M Abdulateef And O.
M. Abdulmajeed. Impact of the electric shock on the embryonic development and
physiological traits in chicks embryo. Indian Journal of Animal Sciences,
2021; 90 (11): 1541–15456.
6.
Yeul, V.S. and
S.S. Rayalu, Unprecedented chitin and
Chitosan: A chemical overview. Journal of Polymers and the Environment,
2013. 21(2): p.
606-614.
7.
Rinaudo, M., Main properties and current applications of
some polysaccharides as biomaterials.
Polymer International, 2008. 57(3): p. 397-430.
8.
Sarmento, B.
and J. das Neves, Chitosan-based systems
for biopharmaceuticals: delivery, targeting and polymer therapeutics. 2012:
John Wiley & Sons.
9.
Varshosaz, J., The promise of chitosan microspheres in drug
delivery systems. Expert opinion on drug delivery, 2007. 4(3): p. 263-273.
10.
Madihally, S.V.
and H.W. Matthew, Porous chitosan
scaffolds for tissue engineering. Biomaterials, 1999. 20(12): p. 1133-1142.
11.
Lehr, C.-M., et
al., In vitro evaluation of mucoadhesive
properties of Chitosan and some other natural polymers. International
Journal of Pharmaceutics, 1992. 78(1-3): p. 43-48.
12.
Suwaid, A. H.
.; Rashid, M. A. .; Taha, M. M. . Genetic Analysis For Combining Ability And
Estimation Of Some Genetic Parameters Of Yield And Its Components In Maize
Using Half Diallel Cross. Journal of Life Science and Applied Research. 2020,
1, 60-64..
13.
Minagawa, T.,
et al., Effects of molecular weight
and deacetylation degree of chitin/Chitosan on wound healing. Carbohydrate polymers, 2007.
67(4): p. 640-644.
14.
Sudarshan, N.,
D. Hoover, and D. Knorr, Antibacterial
action of chitosan. Food Biotechnology, 1992. 6(3): p. 257-272.
15.
Ong, S.-Y., et
al., Development of a chitosan-based
wound dressing with improved hemostatic and antimicrobial properties. Biomaterials,
2008. 29(32): p.
4323-4332.
16.
Heinze, T., New ionic polymers by cellulose
functionalization. Macromolecular Chemistry and Physics, 1998.
199(11): p. 2341-2364.
17.
Alsalami,
F.M.A., Gelatin grafted with drug. Asian
Journal of Green Chemistry. 2(4):
p. 307-317.
18.
AL-Salami,
F.M., A.N. AL-Sharify, and K.J. Kadem, Synthesis
of Histidine-Amoxillin Condensed Drug Polymer. Iraqi National Journal Of
Chemistry, 2012. 45:
p. 126-134.
19.
Firyal, M. and
M. Hameed, Modification of Pepsin-Glycine
with Indomethacin. International Journal of Medical Science and
Dental Research, 2018. 45:
p. 126-134.
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