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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Numerous therapeutic and diagnostic approaches used within a clinical setting depend on the administration of compounds via systemic delivery. Biomaterials at the nanometer scale, as dendrimers, act as delivery systems by improving cargo bioavailability, circulation time, and the targeting of specific tissues. Although evaluating the efficacy of pharmacological agents based on nanobiomaterials is crucial, conducting toxicological assessments of biomaterials is essential for advancing clinical translation. Here, a zebrafish larvae model was explored to assess the biocompatibility of poly(amido amine) (PAMAM), one of the most exploited dendrimers for drug delivery. We report the impact of a systemic injection of polyethylene glycol (PEG)-modified G4 PAMAM conjugated with rhodamine (Rho) as a mimetic drug (PEG–PAMAM–Rho) on survival, animal development, inflammation, and neurotoxicity. A concentration- and time-dependent effect was observed on mortality, developmental morphology, and innate immune system activation (macrophages). Significant effects in toxicological indicators were reported in the highest tested concentration (50 mg/mL PEG–PAMAM–Rho) as early as 48 h post-injection. Additionally, a lower concentration of PEG–PAMAM–Rho (5 mg/mL) was found to be safe and subsequently tested for neurotoxicity through behavioral assays. In accordance, no significative signs of toxicity were detected. In conclusion, the dose response of the animal was assessed, and the safe dosage for future use in theragnostics was defined. Additionally, new methodologies were established that can be adapted to further studies in toxicology using other nanosystems for systemic delivery.

Details

Title
Biological Response Following the Systemic Injection of PEG–PAMAM–Rhodamine Conjugates in Zebrafish
Author
Custódio, Beatriz 1 ; Carneiro, Patrícia 2   VIAFID ORCID Logo  ; Marques, Joana 3 ; Leiro, Victoria 2   VIAFID ORCID Logo  ; Valentim, Ana M 4   VIAFID ORCID Logo  ; Sousa, Mafalda 5 ; Santos, Sofia D 2   VIAFID ORCID Logo  ; Bessa, José 4 ; Pêgo, Ana P 1   VIAFID ORCID Logo 

 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal[email protected] (S.D.S.); ; INEB—Instituto Nacional de Engenharia Biomédica, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal 
 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal[email protected] (S.D.S.); ; INEB—Instituto Nacional de Engenharia Biomédica, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal 
 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal[email protected] (S.D.S.); ; ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal 
 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal[email protected] (S.D.S.); ; IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal 
 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal[email protected] (S.D.S.); 
First page
608
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
19994923
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3059627010
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.