In this work, Casein as a natural polymer was modified with Maleic anhydride a grafted copolymer (A1) ,then the substitution reaction was undergo between grafted maleic anhydride and procaine as amino drug, producing Casein grafted N- procienyl meleamic acid copolymer (A2) as biodegradable polymers a suitable design of drug carrier for  controlled delivery of therapeutic agent to extend period of time and increase the residence time of drug in the system . The prepare new drug copolymer was characterized by FTIR spectroscopy and controlled release was studied in different pH values 1.1and 7.4 at 37C0 .Thermo gravemetric analysis was carried out, which indicated the thermal stability of (A1) and (A2). Keywords:Casein ,Natural polymer ,Grafted copolymer 

H.Awad, Sana

Mohammad Ali., Firyal

English

International Institute for Science, Technology and Education (IISTE): E-Journals

Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  54 Casein Grafted Maleic Anhydride Copolymer and Substituted With Procaine  Firyal Mohammad Ali.1      Sana .H.Awad2 Al-Mustansiriya University, College of Science Department of Chemistry. 1. AL-Mustansiriyah University, College of Science ,Baghdad -Iraq 2.Baghdad University  , College Science for Women ,Department of Chemistry * E-mail of the corresponding author: Abood121996@yahoo.com  Abstract In this work, Casein as a natural polymer was modified with Maleic anhydride a grafted copolymer (A1) ,then the substitution reaction was undergo between grafted maleic anhydride and procaine as amino drug, producing Casein grafted N- procienyl meleamic acid copolymer (A2) as biodegradable polymers a suitable design of drug carrier for  controlled delivery of therapeutic agent to extend period of time and increase the residence time of drug in the system . The prepare new drug copolymer was characterized by FTIR spectroscopy and controlled release was studied in different pH values 1.1and 7.4 at 37C0 .Thermo gravemetric analysis was carried out, which indicated the thermal stability of (A1) and (A2). Keywords:Casein ,Natural polymer ,Grafted copolymer .  Introduction Natural polymers have potential pharmaceutical applications because of their low toxicity ,biocompatibility, and biodegradability  Unstructured proteins are special types of polyelectrolyte with amino acids as their repeating units. [1-3] Casein in milk products is such an unstructured protein and charged regulation its basic properties can be described by the general theory for casein, [4] a predominant phosphoprotein accounting for nearly 80 percent  of proteins which is a naturally occurring and low-cytoxic. [5–6].Biopolymers are an interesting alternative to synthetic polymers because of their potential loading for both hydrophilic and hydrophobic using synthetic chemical reagents and organic solvents is obviously desirable for biomedical applications drugs[7-8]. Dairy proteins, such as sodium Caseinate (SC), a widely used in the food industry as functional ingredients because of their simple production, excellent nutritional value,[9-10] ,and versatile techno-functional properties[11–12]. . Caseins and SC have been conjugated under controlled conditions with different mono-, di-, oligo-, and, polysaccharides including glucose, ribose, fructose , saccharides, maltodextrins, pectins, and dextran; these glycol conjugates exhibit enhanced emulsifying properties over the native protein .[13-14]. Casein, as a drug carrier mainly for the sustained delivery of cytotoxic drugs [15-16-17]. Glutaraldehyde cross-linked casein microspheres were found to be resistant in proteolysis' tract for more than 24 hours and suggested that it could be used as a matrix for the controlled delivery of oral drugs[18].  Casein appears to be a promising carrier for the sustained release of many orally as well as parenteral administered drugs ecosphere carrier systems made from the naturally occurring proteins have attracted considerable attention for several years as a matrix for controlled and sustained release delivery of many drugs [19-20].    Procaine was first synthesize [21-24] shortly after amylocaine, and is the oldest man-made local anesthetic still in clinical use    Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it was also used in dentistry, in some regions procaine is referred to generically as novocaine. It acts mainly by being a sodium channel blocker [22].  Experimental Materials and Instruments:- Casein type Alpha was purchased from Aldrich ,Procaine was purchased from Fluka ,Malic anhydride and Ammonium persulphate (APS)were purchased from Merck .FTIR Spectra were receded by(4000-400)cm-1on a Shimadzu Spectrophotometer .Melting points were determined on Callencamp  MF B-600 melting point apparatus. Electronic Spectra measurements using CINTRAS-UV.visible Spectrophotometers.Thermogravimetric Analysis (TGA) and Deferential Scanning Calorimetry(DSC) were carried out Shimadzu model 50 WS thermal analysis instruments respectively .An accurately weighted of sample was placed in an aluminum cup ad sealed .The experiment consisted of heating the sample from 500C0 under the continues flow of dry nitrogen gas (50ml-min-1) at a heating rate 10 C0 min-1.  Graft Copolymerization of Casein with Maleic anhydride (A1)  [23] In  a screw capped polymerization bottle (2g),(0.02mol) of maleic anhydride was dissolved in 5ml of acetone ,and 5g of Casein was added to the mixture .0.05% of monomer weight of (APS)was dissolved in 1ml of distilled water, then it was added to the mixture. The bottle was flashed with nitrogen gas for few minutes Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  55 inside a glove and firmly stopped  .The mixture was heated at 60-70C0for 20min, the graft copolymer was collected and ,washed  two times with  ether and dried in a vacuum oven at 40C0 the yield %was 90% as white product m.p.177-185C0.  Substitution of procaine with Casein maleic anhydride Copolymer (A2):- 1g of prepared copolymer (A1) was dissolved in 1ml of Dioxane and (o.5g),(0.02mol) of procaine ,the mixture was heated at 60C0 with stirring for 1hr .the solvent was evaporated under vacuum . The yellowish white product was washed three times with ether and dried, drug copolymer (A2) was obtained with 70%.  Controlled Drug Release[24] In 100ml of aqueous buffer  solution such as (phosphate buffer pH 7.4) or acidic solution pH1:1 ,it was added 0.1g of prepared drug copolymer A2,the buffer solution kept at 37C0,with continuously stirred and 3ml of  sample was analyzed by UV.Spectrophotometer and compared many samples in different periods .  Result and Dissections :- In this work Casein was grafted with maleic anhydride ,the grafted polymer containing acid anhydride was reacted with amino drug such as procaine producing grafted N-Drug maleamic acid which allows the  formation of functional  derivative by ring opening of grafted malic anhydride by nucleophilic attack on Casein back bone .Drug  delivery system based on Casein as a biodegradable system which has the ability to release the drug  for the administration of pharmaceutical and biomedical application ,The reaction was showed as Scheme (1)  Scheme (1) :The synthesis Route of The copolymer (A2) Fig (1) and Fig (2) showed FTIR spectra of Casein and A2 respectively. Casein graft maleic anhydride indicated the absorption of (C=O) of anhydride at (1780 and 1750)cm-1due to grafted copolymer A2,Fig (3) ,FTIR spectrum of drug carrier Casein grafted polymer showed the absorption band at 3500-3000 cm-1 attributed to the formation of (OH) stretching of carboxylic acid ,3250cm-1 assignment to NH amide of amic acid in A2 structure .in addition to disappearance of carboxyl group ( -COO-)  of anhydride to (C=O)amic at 1650cm-1and 1720cm-1of carboxylic acid. Fig(4) showed  UV spectrum of controlled drug release at ƛmax320 nm showed the sustain release  due to hydrolysis of amide bond in different pH values, the following mechanism illustrated the hydrolysis at 37C0.See  Scheme (2) and (3) respectively.  Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  56   Scheme (2):Hhydrolysis of Casein N-Maleamic acid in basic medium  Scheme (3):Hydrolysis of Casein N-drug maleamic in acidic  medium This study is included modification  the Casein  as a natural polymer to grafted maleic copolymer  then substituted to its corresponding  N-drug maleamic acid copolymer to enhanced the sustained delivery system through chemical bonds and slowly release under appropriate medium conditions such as pH 7.4 and 1.1at 37C0.Fig(4) UV spectrum which indicated the hydrolysis of A2 drug polymer. We concluded that the hydrolysis in basic medium is higher  than acidic medium this attributed to OH- is more nucleophlic attack on carbonyl of amide than H- and water molecule. Fig (5) TGA and DSC of Casein -g- maleic anhydride (A1)and (A2) exhibit thermal stability ,which recorded  a function of temperature with weight loss of polymer samples as listed in Table (1)    Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  57 Table (1)ThermalDecomposition Temperature for Casein- g-maleic anhydride copolymer  Polymer No. Temp.C0 Weight loss % Mass change Enthalpy J/g TmC0 A1 219.3 229.1  -2.032 -5.40 -2.032 -209.4 300 A2 240 400 -2.75 -10.28 -2.754 -8.84 320 Grafted copolymer A1 indicated high thermal resistance due to incorporated Maleic anhydride copolymer at 300C0 in an enthalpy -209.4 J/g with weight loss 50% . After ring  opening of grafted maleic anhydride to N-procaenylmaleamic  acid grafted on Casein gave higher thermal resistance at 320C0 with 50% weight loss%.in an enthalpy -8.84J/g .The elemental analysis values of N% agreed quite well with the exhibited for the proposed structure of Casein g- N-procaeinyl maleamic acid copolymer A2. Swelling percentage was measured in water ,it was found that high swelling%  of Casein g-N- procainyl maleamic acid A2about 60% indicated high absorption ratio of A2. A novel drug copolymer which concluded as natural local anesthetic action andother uses due to high absorption ratios of water through one day .and sustained drug release for prolong time. In this work new properties in final copolymer were obtained and the pendent carboxylic groups of maleamic acid could be converted  to Na salt through back bone of Casein with more interesting features ,such as swelling% and sustained drug release with low toxicity ,biodegradability with high potential pharmaceutical application due to its potentials loading for both hydrophilic and hydrophobic system.   Figure(1): FTIR Spectrum of Casein   Figure(2):FTIR Spectrum of Casein grafted maleic anhydridecopolymer(A1) Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  58  Figure(3): FTIR Spectrum of Casein (N- Procanylmaliamic acid)copolymer(A2)   Figure(4) UV spectra of controlled release of drug copolymer A2  in pH 7.4and 2.1   Figure(5) TGA and DSC of copolymer of Casein g- maleic anhydride Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  59  Figure(6) TGA and DSC of Casein g –[N- procainylMaleamicA2]  Acknowledgment The authors are grateful for the functional support obtained from Al-Mustansirya University College of science department of chemistry and women College of Science .  References 1-Elzoghby AO, Abo El-Fotoh WS, Elgindy NA. Casein-based formulations as promising controlled release drug delivery systems. Journal of Controlled Release.2011;153(3):206–216. 2-Chen ,L.,RemondettoGE.Food protein –based materials as nutraceuticaldelivery.system.Trends Food Sc.Tendnd .2006 ,17.272-283 3- Arora N.,Carg T.,Biland A., Review of Casein production and Casein based nano- formulation , International Research J.,of Pharmacy IRJP 2012,3,1 4-.Kohori, F.; Yokoayma, M.; Sakai, K.; Okano, The casein micelle and milk coagulation. T. J Controlled Release 2002, 78, 155–16 5-Sanchez, C.; Renard, D The biological function of casein:.Int J Pharm 2002, 242, 319–324 6-Lund, M. Casein association and micelleformation,Electrostatic chameleons in biological systems. Journal of the American Chemical Society 2010., 111-14. 7-Yao, L., de Ruiter, G. C., Wang, H., Knight, A. M., Spinner, R. J., Yaszemski, M. J., Windebank, A. J. &Pandit, A.,Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit. Biomaterials.0210  31, 5789–5797 8-Alvarez-Perez, M.A.,Guarino,V., Cirillo,V.&Ambrosio, L. Influence of gelatin cues in PCL electrospun membranes on nerve outgrowth. Biomaterials.2010.11, 5347–5349 9-Ghasemi-Mobarakeh, L., Prabhakaran, M. P., Morshed, M., Nasr-Esfahani, M. H. & Ramakrishna, S. Electrospunpoly(epsilon-caprolactone)/gelatin nanofibrous. Biomaterials.2008 . 29, 4532–4539 10- Wang, L. S., Chung, J. E., Chan, P. P. &Kurisawa, M. Injectable biodegradable hydrogels with tunable mechanical properties for the stimulation of neurogenesic differentiation of human mesenchymal stem cells in 3D culture. Biomaterials.2010 . 31, 1148–1157 11-Mu, M., X. Pan, P. Yao, and M. Yiang.. Acidic solution properties of β-casein-graft-dextran copolymer prepared through Maillard reaction. J. Colloid Interface Sci.2006. 301:98–106 12-O’Regan, J., and D. M. Mulvihill. 2009. Preparation, characterisation and selected functional properties of sodium caseinate–maltodextrin conjugates. Food Chem. 115:1257–1267 13-Oliver, C. M., L. D. Melton, and R. A. Stanley.. Creating proteins with novel functionality via the Maillard reaction: A review. Crit. Rev. Food Sci.2006a. Nutr. 46:337–350 14-Soria, A. C., and M. Villamiel.. Effect of ultrasound on the technological properties and bioactivity of food: A review. Trends Food Sci.2010. Technol. 21:323–331 15-Ju H. K, Kim S Y and Lee Y. M. “pH/temperature-responsivebehaviours of semi-IPN and comb-type graft hydrogels composed of alginate and poly(N-isopropylacrylamide)” Polymer. 2001., 42, , 6851-6857 16-Murali Mohan Babu G V, Prasad D. S, Narayan P. S and Raman Murthy K. V. “New system for microencapsulation of Diclofenac Sodium by using Gum Karaya and Chitosan” Saudi Pharm. J. 2001.. 9, , 169-Journal of Natural Sciences Research                                                                                                                                                www.iiste.org ISSN 2224-3186 (Paper)   ISSN 2225-0921 (Online) Vol.5, No.12, 2015  60 178. 17-Morimoto Y and Fujimoto, S. “Albumin microspheres as drug carrier” CRC Critical Reviews in Therapeutic Drug Carrier Systems.1985.. 1, 2, ,. 19-63  18-Seong-Hoon K, Byoung-Ki L, Fangfang S, Kwangnak K, Su-Chat R, Hong-Sung K and Jaebeom L. “Preparation of high flexible Composite Film of Hydroxyapatite and Chitosan” Polymer Bulletin. 2009. 62, 1, , 111-118 19-Deng, J., L. Wang, L. Liu and W. Yang,. Developments and new applications of UV-induced surface graft polymerizations. Progress in Polymer Science, 2009. 34(2): 56-193 20-Zhao, J., D. Shanyi and T. Guishan,.Surface modification of acrylic fiber by grafting of casein. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry. 2007. 44(3): 299-304.  21-Mahato R (ed) Biomaterials for delivery and targeting of proteins and nucleic acids. 200563(3):136–151.. 22-Barber  M., Giesecke U., Reichert A., and Minas W.. Industrial enzymatic production of cephalosporin-based β-lactams. Adv. Biochem. Eng. Biotechnol. 2004.88: 179–215.  23-Hillery AM, Lloyd AW, SwarbrickJ .,Drug delivery and targeting for pharmacists and pharmaceutical scientists. 2001.Science 249:1527–1533 24-Firyal M.A.,TaghreedH.Al-Noor and SaifM.Synthesis and Characterization of Gelatin-G-Poly (AcryloylAmide) Proflavine and Controlled Release Study Chemical and Process Engineering Research .2015., 32: 53-61.     The IISTE is a pioneer in the Open-Access hosting service and academic event management.  The aim of the firm is Accelerating Global Knowledge Sharing.  More information about the firm can be found on the homepage:  http://www.iiste.org  CALL FOR JOURNAL PAPERS There are more than 30 peer-reviewed academic journals hosted under the hosting platform.   Prospective authors of journals can find the submission instruction on the following page: http://www.iiste.org/journals/  All the journals articles are available online to the readers all over the world without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself.  Paper version of the journals is also available upon request of readers and authors.   MORE RESOURCES Book publication information: http://www.iiste.org/book/ Academic conference: http://www.iiste.org/conference/upcoming-conferences-call-for-paper/   IISTE Knowledge Sharing Partners EBSCO, Index Copernicus, Ulrich's Periodicals Directory, JournalTOCS, PKP Open Archives Harvester, Bielefeld Academic Search Engine, Elektronische Zeitschriftenbibliothek EZB, Open J-Gate, OCLC WorldCat, Universe Digtial Library , NewJour, Google Scholar   

Casein Grafted Maleic Anhydride Copolymer and Substituted With Procaine

https://www.iiste.org/Journals/index.php/JNSR/article/download/23487/24127

Casein Grafted Maleic Anhydride Copolymer and Substituted With Procaine

Abstract

Similar works

Full text

Available Versions

International Institute for Science, Technology and Education (IISTE): E-Journals