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Encapsulation of SAAP-148 in Octenyl Succinic Anhydride-Modified Hyaluronic Acid Nanogels for Treatment of Skin Wound
Miriam E van Gent1, Tom van Baaren1, Sylvia N Kłodzińska2
1Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Abstract:
Chronic wound infections colonized by bacteria are becoming more difficult to treat with current antibiotics due to the development of antimicrobial resistance (AMR) as well as biofilm and persister cell formation. Synthetic antibacterial and antibiofilm peptide (SAAP)-148 is an excellent alternative for treatment of such infections but suffers from limitations related to its cationic peptidic nature and thus instability and possible cytotoxicity, resulting in a narrow therapeutic window. Here, we evaluated SAAP-148 encapsulation in nanogels composed of octenyl succinic anhydride (OSA)-modified hyaluronic acid (HA) to circumvent these limitations. SAAP-148 was efficiently (>98%) encapsulated with high drug loading (23%), resulting in monodispersed anionic OSA-HA nanogels with sizes ranging 204-253 nm. Nanogel lyophilization in presence of polyvinyl alcohol maintained their sizes and morphology. SAAP-148 was sustainedly released from lyophilized nanogels (37-41% in 72 h) upon reconstitution. Lyophilized SAAP-148-loaded nanogels showed similar antimicrobial activity as SAAP-148 against planktonic and biofilm-residing AMR Staphylococcus aureus and Acinetobacter baumannii. Importantly, formulated SAAP-148 showed reduced cytotoxicity against human erythrocytes, primary human skin fibroblasts and human keratinocytes. Additionally, lyophilized SAAP-148-loaded nanogels eradicated AMR S. aureus and A. baumannii colonizing a 3D human epidermal model, without inducing any cytotoxicity in contrast to SAAP-148. These findings indicate that OSA-HA nanogels increase SAAP-148's therapeutic potential for treatment of skin wound infections.
Insights
This study developed nanogels to improve the synthetic antibacterial and antibiofilm peptide (SAAP)-148 for treating chronic wound infections. The nanogel formulation enhanced SAAP-148
Area of Science:
- Biomaterials science
- Nanotechnology
- Infectious diseases
Background:
- Chronic wound infections are challenging due to antimicrobial resistance (AMR), biofilms, and persister cells.
- Synthetic antibacterial and antibiofilm peptide (SAAP)-148 shows promise but has limitations like instability and cytotoxicity.
- Octenyl succinic anhydride (OSA)-modified hyaluronic acid (HA) nanogels offer a potential solution for peptide delivery.
Purpose of the Study:
- To encapsulate SAAP-148 into OSA-HA nanogels to overcome its limitations.
- To evaluate the stability, drug release, antimicrobial activity, and cytotoxicity of the SAAP-148-loaded nanogels.
- To assess the efficacy of the nanogel formulation in a 3D human skin model.
Main Methods:
- SAAP-148 was encapsulated into OSA-HA nanogels with high efficiency and loading.
- Nanogels were lyophilized for stability and characterized for size and morphology.
- Sustained release of SAAP-148 from lyophilized nanogels was measured.
- Antimicrobial activity against planktonic and biofilm bacteria was tested.
- Cytotoxicity was assessed using human cells and erythrocytes.
- Efficacy was evaluated in a 3D human epidermal model.
Main Results:
- SAAP-148 was efficiently encapsulated (>98%) in anionic OSA-HA nanogels (204-253 nm) with high drug loading (23%).
- Lyophilized nanogels maintained size and morphology, enabling sustained SAAP-148 release (37-41% in 72 h).
- The nanogel formulation retained antimicrobial activity against AMR *Staphylococcus aureus* and *Acinetobacter baumannii*.
- Formulated SAAP-148 exhibited reduced cytotoxicity against human cells and erythrocytes.
- Lyophilized SAAP-148-loaded nanogels eradicated bacteria in a 3D skin model without cytotoxicity.
Conclusions:
- OSA-HA nanogels effectively encapsulate and stabilize SAAP-148, improving its therapeutic profile.
- The nanogel formulation enhances SAAP-148's efficacy against resistant bacteria in chronic wound models.
- This approach offers a promising strategy to overcome SAAP-148 limitations for treating skin infections.
