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1.
Daru ; 31(1): 1-12, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37209247

RESUMO

BACKGROUND: To have a better and longer effect, botulinum neurotoxin (BoNT) is injected several times in a treatment course, which could increase side effects and cost. Some of the most cutting-edge strategies being investigated for proteins to their physiologic targets involve the reformulation of BoNT based on peptide-based delivery systems. For this purpose, cell-penetrating peptides (CPPs) are of particular interest because of their capacity to cross the biological membranes. OBJECTIVES: A short and simple CPP sequence was used as a carrier to create nanocomplex particles from BoNT/A, with the purpose of increasing toxin entrapment by target cells, reducing diffusion, and increasing the duration of the effect. METHOD: CPP-BoNT/A nanocomplexes were formed by polyelectrolyte complex (PEC) method, considering the anionic structure of botulinum toxin and the cationic CPP sequence. The cellular toxicity, and absorption profile of the complex nanoparticles were evaluated, and the digit abduction score (DAS) was used to assess the local muscle weakening efficacy of BoNT/A and CPP-BoNT/A. RESULTS: The provided optimized polyelectrolyte complex nanoparticles had a 244 ± 20 nm particle size and 0.28 ± 0.04 PdI. In cellular toxicity, CPP-BoNT/A nanocomplexes as extended-release formulations of BoNT/A showed that nanocomplexes had a more toxic effect than BoNT/A. Furthermore, the comparison of weakening effectiveness on muscle was done among nanoparticles and free toxin on mice based on the digit abduction score (DAS) method, and nanocomplexes had a slower onset effect and a longer duration of action than toxin. CONCLUSION: Using PEC method allowed us to form nanocomplex from proteins, and peptides without a covalent bond and harsh conditions. The muscle-weakening effect of toxin in CPP-BoNT/A nanocomplexes showed acceptable efficacy and extended-release pattern.


Assuntos
Toxinas Botulínicas Tipo A , Peptídeos Penetradores de Células , Animais , Camundongos , Toxinas Botulínicas Tipo A/metabolismo , Toxinas Botulínicas Tipo A/farmacologia , Peptídeos Penetradores de Células/farmacologia , Polieletrólitos
2.
Chem Biol Drug Des ; 80(5): 639-46, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22846609

RESUMO

In the last decade, almost one-third of the newly discovered drugs approved by the US FDA were biomolecules and biologics. Effective delivery of therapeutic biomolecules to their target is a challenging issue. Innovations in drug delivery systems have improved the efficiency of many of new biopharmaceuticals. Designing of novel transdermal delivery systems has been one of the most important pharmaceutical innovations, which offers a number of advantages. The cell-penetrating peptides have been increasingly used to mediate delivery of bimolecular cargoes such as small molecules, small interfering RNA nucleotides, drug-loaded nanoparticles, proteins, and peptides, both in vitro and in vivo, without using any receptors and without causing any significant membrane damage. Among several different drug delivery routes, application of cell-penetrating peptides in the topical and transdermal delivery systems has recently garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries. In this review, we discuss history of cell-penetrating peptides, cell-penetrating peptide/cargo complex formation, and their mechanisms of cell and skin transduction.


Assuntos
Peptídeos Penetradores de Células/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas/administração & dosagem , Pele/metabolismo , Administração Cutânea , Sequência de Aminoácidos , Animais , Peptídeos Penetradores de Células/metabolismo , Portadores de Fármacos/metabolismo , Humanos , Dados de Sequência Molecular , Absorção Cutânea
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