# Cyclodextrin Polymers as a Promising Drug Carriers for Stabilization of Meropenem Solutions
## 3 Results and Discussion
### DLS and NTA Analysis  
It is well-known, that HPCD polymerization yield large molecules [18] that are able to form nanoparticles. As such, in order to evaluate the role of cross-linking agents we compared hydrodynamic diameters and \(\zeta\)-potentials for all types of synthetized polymers via nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) [19].  
The obtained data are summarized in Table 1. According to NTA data, the HPCD polymers form homogeneous nanoparticles with an average diameter of 150 nm. The DLS provided higher values (250-300 nm) that might be caused by the presence of hydrophilic particle's shell.  
The average size of HPCD-CA polymers is smaller than HPCD-SA, apparently due to the three functional groups in CA that are available for binding which might cause the formation of a denser polymer structure.  
HPCD-HMD demonstrates the hydrodynamic diameter of approximately 150 nm, while MP's imprinting into HPCD-HMD polymer leads to the slight increase of particle size.  
\begin{table}
\begin{tabular}{l c c c c c c} \hline  & **Method** & **HPCD** & **HPCD-CA** & **HPCD-SA** & **HPCD-HMD** & **HPCD-HMD-MP\({}_{\text{im}}\)** \\ \hline Hydrodynamic & NTA & \(\approx\)0.15  & 120.1 \(\pm\) 3.2 & 199.2 \(\pm\) 18.2 & 142.5 \(\pm\) 13.5 & 178.8 \(\pm\) 10.2 \\ diameter, nm & DLS & \(\approx\)0.15 [OTNOTE:]Footnote : The size of HPCD is assumed as the size of \(\beta\)-CD [6]; \({}^{2}\)—\(\zeta\)-potential of HPCD-CA isn’t determined, since a chemical reaction may occur under the experimental conditions (decarboxylation).[ENDFOOTNOTE] & 245 \(\pm\) 15 & 283 \(\pm\) 21 & 220 \(\pm\) 17 & 289 \(\pm\) 22 \\ \hline \(\zeta\)-potential, mV & DLS & 0.5 \(\pm\) 0.3 & – 2 & 5.6 \(\pm\) 2.1 & 14.7 \(\pm\) 0.4 & –2.9 \(\pm\) 0.3 \\ \hline \end{tabular}
\end{table}
Table 1: The size and \(\zeta\)-potential of HPCD polymers, H\({}_{2}\)O, 25 \({}^{\circ}\)C.  
Figure 1: The scheme of HPCD-Citric acid, HPCD-Succinic acid, HPCD-HMD, and HPCD-HMD-MP\({}_{\text{im}}\) polymer synthesis.  
We suppose this effect might be caused by the complexation of MP with HPCD at the first synthesis stage, which increases the spatial distance between CD-torus for linker binding.  
The \(\zeta\)-potential value usually represents valuable data for colloidal particles and, in the case of HPCD-CA, the determination of accurate values was challenging. We suppose a chemical reaction (decarboxylation of a free carboxyl group) may occur under the experimental conditions. Nevertheless, we expect negative surface charge. For HPCD-SA (synthesized with bifunctional linker), the \(\zeta\)-potential is close to neutral. Interestingly, HPCD-HMD demonstrates strong positive \(\zeta\)-potential. This finding will be discussed further.  
In the case of HPCD-HMD-MP\({}_{\text{im}}\), the \(\zeta\)-potential is significantly lower. MP is predominantly zwitterionic in aqueous solution [20], and its \(\zeta\)-potential is \(-3.72\) mV [21]. MP's imprinting into HPCD polymer matrix lead to the decrease of particles' \(\zeta\)-potential that might be due to interactions between MP and the HPCD-HMD polymer network. We have recently obtained similar results for resembling imprinted systems based on sulfobutyl ether \(\beta\)-cyclodextrintrim, HMD, and moxifloxacin [22]. The imprinting of moxifloxacin in cyclodextrin's matrix causes the neutralization of particles' \(\zeta\)-potential. We would like to stress that moxifloxacin was uniformly distributed over the entire volume of the particle. Thus, we assume that cyclodextrin polymers with imprinted MP or moxifloxacin might have similar properties.  
Thus, the comparison of the data from DLS and NTA reveals significant differences between both two types of DDS (imprinted and not imprinted) and between polymers that were obtained with different cross-linking agents. The average Mr value is 150 kDa. In order to discover the physico-chemical reasons of this phenomenon we have studied the structure of obtained systems in detail via spectroscopic methods.