## 1 Introduction  
Beta-lactam antibiotics have been the most prominent defense worldwide [1] and have been chosen as one of the essential medicines by the World Health Organization (WHO) [2] for the treatment of bacterial infections. Beta-lactam antibiotics inhibit bacterial cell membrane synthesis showing an antibacterial effect [3]. In this research, ampicillin trihydrate and cefalexin monohydrate were selected for the synthesis of drug-functionalized maleic anhydride copolymers (DFMACs). Those antibiotics were chosen from two subgroups: penicillin (ampicillin) and cephalosporions (cefalexin) to understand the behavior of \(\beta\)-lactam antibiotics in general. Although cefalexin (CEF) [4] and ampicillin (AMP) are widely used, broad-spectrum antibiotics, they have poor pharmacokinetics. In the treatment of chronic infections, high dosages of antibiotics can cause cumulative toxicity and a burden on the kidneys [4]. Additionally, antibiotic resistance can develop due to the poor pharmacological properties of drugs [5]. Therefore, it is crucial that the pharmacological properties of these antibiotics, such as stability, activity and polydispersity, should be improved while maintaining antibacterial effect. Bioactive polymeric materials are suitable candidates for enhancing the physical and pharmacological properties of drugs [6] due to their desirable properties such as lower dosages and better stability [7]. Although there have been several methods to prepare bioactive polymeric materials, the chemical conjugation method steps forth with an increased drug loading capacity [8]. The pharmacokinetics of the polymer-drug conjugation often mirror the pharmacokinetics of the polymer itself [9]. Therefore, candidate polymers as drug conjugates should meet certain criteria such as biocompatibility, possessing suitable functional groups like -COOH, -NH2, -OH, etc., for covalent conjugation with drugs, water solubility, a low PDI value and be readily available [10]. Maleic anhydride-derived polymers meet these criteria for improving the pharmacological properties of drugs due to their special properties [11]. Maleic anhydride copolymers are notable for their unique properties such as biocompatibility, low toxicity [12; 13], easy availability, ability to vary hydrophilicity and hydrophobicity depending on comonomer choice and water solubility in pharmaceutical and medical applications [14; 15]. Thus, it is possible to modify and enhance properties and usage areas of this class of polymers [11]. Additionally, the chemical structure allows mild reactions with drugs avoiding contamination with impurities [15]. Reactivity of the anhydride group with nucleophilic agents (OH, NH) and reproducible structures [16] make the maleic anhydride copolymers a suitable candidate. The drugs can be attached to maleic anhydride copolymers with ease, either through the anhydride cycle or through the comonomer reactive groups [14; 15]. There are many examples of maleic anhydride-based materials used as adhesives, biomedical devices and drug delivery systems in the literature [17; 18; 19]. Maleic anhydride copolymers can be used as drugs, as a support to bioactive molecules or as conjugates in drug-controlled release systems [15]. The covalent binding of drugs to macromolecular structures such as polymers forms polymer-drug conjugates. One of the main aims of the usage of polymer-drug conjugates is to enhance the properties of the selected drug in terms of stability, activity, bioavailability, etc. [20]. One of the maleic anhydride-derived copolymers (poly(styrene-alt-maleic anhydride) was covalently conjugated with acetaminophen drug to improve the pharmacological properties [21]. Therefore, in this study, three different maleic anhydride copolymers were chosen for their varying degrees of hydrophilicity: poly(methyl vinyl alt-maleic anhydride) (PMVEMA), poly(ethylene alt-maleic anhydride) (PEMA) and poly(isobutylene alt-maleic anhydride) (PIBMA).