# Steering the Clinical Translation of Delivery Systems for Drugs and Health Products
## 3 Poster Presentations
### Polysaccharide Hydrogels for the Stabilization and Controlled Release of Ionic Cargo  
[PERSON] 1, [PERSON] 1,*, [PERSON] 1, [PERSON] 2, [PERSON] 2, [PERSON] 2 and [PERSON] 1  
1 School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino (MC), Italy  
2 Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80138 Napoli, Italy  
* Correspondence: [EMAIL_ADDRESS]  
Polysaccharides (PLS) are biodegradable and biocompatible and polymers, derived from renewable sources and showing great potential for several biomedical applications, such as the prevention and treatment of staphylococcal infections [25]. A strategy to fight these infections is the use of PLS-based delivery systems for the controlled release of antimicrobial drugs. PLS-based in situ-forming hydrogels are able to improve the efficacy of the loaded drug(s) while overcoming different drawbacks like: Systemic drug toxicity, high peak plasma concentrations and rapid drug degradation. In this work we investigated acidic PLS hydrogels as matrices for the stabilization and the release of vancomycin (VAN) [26; 27]. Hyaluronic acid (HA), alginic acid (ALG), propylene glycol alginate (PGA) and xanthan gum (XA) were used as acidic PLS, while VAN was selected as drug. PLS-VAN solutions containing a fixed amount of polysaccharide (5 mg/mL) and PLS-VAN hydrogels at gel-point concentrations were formulated in phosphate buffer at pH 7.4. Chemical stability tests of VAN formulated into PLS-VAN solutions and hydrogels were performed for 22 days by HPLC-DAD-MS. Placebo hydrogels and drug-loaded systems were characterized by rheological analysis at 37 \({}^{\circ}\)C. VAN release studies were performed at pH 7.4 and 37 \({}^{\circ}\)C for 70 h. The antimicrobial activity of the complexes was tested against _Staphylococcus aureus_ at 10\({}^{6}\) CFU/mL after 24, 48 and 70 h via microdilution method. VAN chemical stability tests showed that the glycopeptide antibiotic rapidly degrades via deamidation processes, when dissolved in phosphate buffer at pH 7.4, reaching a residual concentration of native VAN of 35% after 22 days. Conversely, when VAN is physically encapsulated into acidic polysaccharide networks at physiological conditions, it was found that the deamidation kinetics of the glycoprotein is decreased. In particular, XAN-VAN, PGA-VAN and HA-VAN hydrogels preserve VAN structure increasing with +25% its stability after 22 days compared with VAN solution (Figure 9). Moreover, results show that not all polymers were able to stabilize the drug to the same extent. VAN stabilization dependsnot only by physical encapsulation but also by ionic interaction between drug and polysaccharide. In addition, the formation of ionic complexes affects rheological characteristics of the systems: the presence of the peptide confers to PGA and XAN gels an increase of both viscoelastic moduli while for HA formulation leads to a transition from an entangled solution to a gel-like behavior. Release tests revealed that at least 60% of VAN was released within 3 days for all formulations. Antimicrobials susceptibility tests show a significant bacteria reduction compared to VAN solution. In conclusion, these designed formulations can preserve VAN structural stability enhancing its antimicrobial activity in physiological environment thanks to the physical encapsulation and self-assembling ionic complexes configuration. Furthermore, VAN-PLS gels could be potentially used as functional coating and as injectable hydrogels in the prevention and treatment of implant-associated or wound infections. **Acknowledgments:** The authors acknowledge the E C for funding ISPIC--H2020-MSCA-ITN-2015 (Grant No. 675743); CHARMED--H2020-MSCA-RISE-2016 (Grant No. 734684); CANCER--H2020-MSCA-RISE-2017 (Grant No. 777682).