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Preparation and antimicrobial evaluation of polyion complex (PIC) nanoparticles loaded with polymyxin B.

ABSTRACT: Here, we describe novel polyion complex (PIC) particles for the delivery of Polymyxin B (Pol-B), an antimicrobial peptide currently used in the clinic as a last resort antibiotic against multidrug-resistant gram-negative bacteria. A range of conditions for the controlled assembly of Pol-B with poly(styrene sulphonate) (PSS) has been identified which let us prepare stable colloidal PIC particles. This way, PIC particles containing different Pol-B:PSS ratios have been prepared and their stability under simulated physiological conditions (i.e. pH, osmotic pressure and temperature) characterised. Furthermore, preliminary evaluation of the antimicrobial activity of these Pol-B containing PIC particles has been performed, by monitoring their effect on the growth of Pseudomonas aeruginosa, an opportunistic gram-negative bacterium.

SUBMITTER: Insua I

PROVIDER: S-EPMC5327956 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Preparation and antimicrobial evaluation of polyion complex (PIC) nanoparticles loaded with polymyxin B.

Insua Ignacio I Majok Sieta S Peacock Anna F A AF Krachler Anne Marie AM Fernandez-Trillo Francisco F

European polymer journal 20170201

Here, we describe novel polyion complex (PIC) particles for the delivery of Polymyxin B (Pol-B), an antimicrobial peptide currently used in the clinic as a last resort antibiotic against multidrug-resistant gram-negative bacteria. A range of conditions for the controlled assembly of Pol-B with poly(styrene sulphonate) (PSS) has been identified which let us prepare stable colloidal PIC particles. This way, PIC particles containing different Pol-B:PSS ratios have been prepared and their stability ...[more]

PMID: 28280277

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Project description:Human African trypanosomiasis (HAT), also commonly known as sleeping sickness, is a neglected tropical disease affecting millions of people in poorly developed regions in sub-Saharan Africa. There is no satisfactory treatment for this infection. The investment necessary to bring new drugs to the market is a big deterrent to drug development, considering that the affected communities form a non-lucrative sector. However, natural products and many sesquiterpene lactones (STLs) in particular are very strong trypanocides. Research and applications of nano-drug delivery systems such as nanoparticles (NPs) have undergone unprecedented growth in the recent past. This is mainly due to the advantages offered by these systems, such as targeted delivery of the drug to the place of action (cell, parasite, etc), sustained release of the drug, increased bioavailability, reduced drug dosage, and reduction of undesired side effects, among others. In this study, the STLs α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, all trypanocides, were loaded into polylactic acid (PLA) NPs through an emulsification-diffusion method. The NPs were stable, homogenous, and spherical in shape with a rounded knotty depression like a navel orange. The average particle sizes were 202.3, 220.3, 219.5, 216.9, and 226.4 nm for α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs had encapsulation efficiencies of 94.6, 78.1, 76.8, 60.7, and 78.9% for α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs loaded with arglabin, vernolepin, and eucannabinolide exhibited considerable antitrypanosomal activity against Trypanosoma brucei rhodesiense (Tbr) with free drug equivalent IC50 values of 3.67, 1.11 and 3.32 µM, respectively. None of the NP formulations displayed cytotoxicity towards mammalian cells (rat skeletal myoblast cell line L6). These results provide new insights into the possibility of incorporating STLs into nanoparticles, which may provide new options for their formulation in order to develop new drugs against HAT.

Project description:The encapsulation of peptides and proteins in nanosystems has been extensively investigated for masking unfavorable biopharmaceutical properties, including short half-life and poor permeation through biological membranes. Therefore, the aim of this work was to encapsulate a small antimicrobial hydrophilic peptide (H-Ser-Pro-Trp-Thr-NH2, FS10) in PEG-PLGA (polyethylene glycol-poly lactic acid-co-glycolic acid) nanoparticles (Nps) and thereby overcome the common limitations of hydrophilic drugs, which because they facilitate water absorption suffer from rapid degradation. FS10 is structurally related to the well-known RNAIII inhibiting peptide (RIP) and inhibits S. aureus biofilm formation. Various parameters, including different method (double emulsion and nanoprecipitation), pH of the aqueous phase and polymeric composition, were investigated to load FS10 into PEG-PLGA nanoparticles. The combination of different strategies resulted in an encapsulation efficiency of around 25% for both the double emulsion and the nanoprecipitation method. It was found that the most influential parameters were the pH-which tailors the peptides charge-and the polymeric composition. FS10-PEG-PLGA nanoparticles, obtained under optimized parameters, showed size lower than 180 nm with zeta potential values ranging from -11 to -21 mV. In vitro release studies showed that the Nps had an initial burst release of 48-63%, followed by a continuous drug release up to 21 h, probably caused by the porous character of the Nps. Furthermore, transmission electron microscopy (TEM) analysis revealed particles with a spherical morphology and size of around 100 nm. Antimicrobial assay showed that the minimum inhibitory concentration (MIC) of the FS10-loaded Nps, against S. aureus strains, was lower (>128 µg/mL) than that of the free FS10 (>256 µg/mL). The main goal of this work was to develop polymeric drug delivery systems aiming at protecting the peptide from a fast degradation, thus improving its accumulation in the target site and increasing the drug-bacterial membrane interactions.

Dataset Information

Preparation and antimicrobial evaluation of polyion complex (PIC) nanoparticles loaded with polymyxin B.

Publications

Preparation and antimicrobial evaluation of polyion complex (PIC) nanoparticles loaded with polymyxin B.

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