Abstract
Nanoparticles exhibit potential as drug carriers in biomedicine due to their high surface-to-volume ratio that allows for facile drug loading. Nanosized drug delivery systems have been proposed for the delivery of biologics facilitating their transport across epithelial layers and maintaining their stability against proteolytic degradation. Here, we capitalize on a nanomanufacturing process famous for its scalability and reproducibility, flame spray pyrolysis, and produce calcium phosphate (CaP) nanoparticles with tailored properties. The as-prepared nanoparticles are loaded with bovine serum albumin (model protein) and bradykinin (model peptide) by physisorption and the physicochemical parameters influencing their loading capacity are investigated. Furthermore, we implement the developed protocol by formulating CaP nanoparticles loaded with the LL-37 antimicrobial peptide, which is a biological drug currently involved in clinical trials. High loading values along with high reproducibility are achieved. Moreover, it is shown that CaP nanoparticles protect LL-37 from proteolysis in vitro. We also demonstrate that LL-37 retains its antimicrobial activity against Escherichia coli and Streptococcus pneumoniae when loaded on nanoparticles in vitro. Therefore, we highlight the potential of nanocarriers for optimization of the therapeutic profile of existing and emerging biological drugs.
Highlights
Biological drugs, called biologics, are therapeutics that contain one or more active substances made by or derived from a biological source [1]
We study the loading on calcium phosphate (CaP) nanoparticles of two different specific surface area (SSA)/sizes of two biomacromolecules, bovine serum albumin (BSA) and bradykinin as model protein and peptide, respectively
We show here the engineering of CaP nanoparticles by flame spray pyrolysis (FSP) and evaluate their loading capacity as carriers of biological drugs
Summary
Biological drugs, called biologics, are therapeutics that contain one or more active substances made by or derived from a biological source [1]. Biologics exhibit high potency coupled with target specificity, there are some important challenges for their broad and effective employment: (i) their transport across various epithelial layers, such as skin and mucus, is limited due to their large size, (ii) they typically suffer from poor bioavailability via the oral route and, can only be administered systemically (e.g., by injection) [3], (iii) they are susceptible to enzymatic degradation in tissues and plasma and their circulation half-life is shortened To address these challenges, nanosized drug delivery systems have been proposed as a promising strategy for the delivery of biologics [4]. Nanoparticles can be used as drug carriers due to their
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