# Cyclodextrin Polymers as a Promising Drug Carriers for Stabilization of Meropenem Solutions
## 1 Introduction  
Today, multidrug-resistant bacteria provide a severe threat for people all over the world, and very few antibiotics, mostly from the reserve group (according to the WHO AWaRe classification), are available for treatment of this kind of infection [1].  
Meropenem (MP) is one the key antibacterial drugs active against several resistant bacteria [2; 3]. MP inhibits cell wall synthesis and usually provides bactericidal effects with a wide spectrum of action including Gram-negative along with _Enterobacteriaceae_ family and Gram-positive bacteria [4]. Despite high antibacterial activity, the application of MP in therapy is still limited due to its low solubility in aqueous media and rapid degradation upon storage [5]. In order to overcome these drawbacks, one should apply drug delivery systems (DDS) with improved biopharmaceutical properties and high biocompatibility. Moreover, there are several more requirements for DDS, e.g., high encapsulation efficacy, long-term stability upon storage, prolonged release, etc. One of the most promising DDS for MP are \(\beta\)-cyclodextrinatrins (CD), cyclic oligosaccharides consisting of seven glucopyranose units linked by \(\alpha\)-(1,4)-bonds. CDs are produced from starch using enzymatic conversion by cyclodextrin glycosyltransferase and \(\alpha\)-amylases, thus CD are biocompatible and biodegradable [6; 7].  
The glucopyranose units in CD create a torus-like structure with a hydrophilic outer surface, which defines CD's high solubility in water and hydrophobic cavity, suitable for \"guest-host\" complex formation with hydrophobic drugs [8]. The formation of a complex with CD improves solubility, stability, and bioavailability of the drugs, furthermore, CDs are approved by the FDA as DDS [9]. Several researchers have demonstrated that CD strengthens drug absorption through the biological barriers, including the blood-brain barrier, because of changing drug-transport properties through lipophilic barriers and affecting membrane fluidity to reduce the barrier function [6; 10; 11; 12].  
Besides initial CDs, many up to date CD derivatives have been synthesized by reactions of esterifications, etherifications, or aminations [10]. The modified CD provides enhanced solubility and stability against oxidation and light, also different substituents regulate the chemical activity of CD [6; 13].  
However, when it comes to the fine tailoring of DDS and managing the biopharmaceutical properties of final drug formulation, one desires additional DDS's properties, for instance, prolonged drug release and the increased bioavailability. From this perspective, the new era of CD-based DDS is coming with CD polymers constructed from different CDs united in one molecular structure by means of small molecules--linkers. Upon shifting from monomeric CDs to polymeric systems, one discovers several new parameters, such as the degree of polymerization, the nature of the linker, the density of crosslinks, etc., which will potentially allow fine-tuning the DDS and obtain its desirable properties. Moreover, significant dosage reduction and simplification of drug regimens can be achieved using CD polymers [10]. Thus, the main benefits of CD polymers as DDS make them potentially applicable for MP delivery to overcome the severe infections that are caused by multidrug resistant bacteria.  
Here, we aimed to design DDS for MP based on the polymers of 2-hydroxypropyl-\(\beta\)-CD (HPCD) and investigate the main patterns of interaction between the drug and carrier by the various spectroscopic methods.