Studying the stability of polymer nanoparticles by size exclusion chromatography of radioactive polymers.

The properties of nanomedicines will influence how they can deliver drugs to patients reproducibly and effectively. For conventional pharmaceutical products, Chemistry, Manufacturing and Control (CMC) documents require monitoring stability and storage conditions. For nanomedicines, studying these important considerations is hindered by a lack of appropriate methods. In this paper, we show how combining radiolabelling with size exclusion chromatography, using a method called SERP (for Size Exclusion of Radioactive Polymers), can inform on the in vitro degradation of polymer nanoparticles. Using nanoparticles composed of biodegradable poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA), we show that SERP is more sensitive than dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to detect degradation. We also demonstrate that the properties of the polymer composition and the nature of the aqueous buffer affect nanoparticle degradation. Importantly, we show that minute changes in stability that cannot be detected by DLS and NTA impact the pharmacokinetic of nanoparticles injected in vivo. We believe that SERP might prove a valuable method to document and understand the pharmaceutical quality of polymer nanoparticles.

Encapsulation of conjugated linoleic acid and ruminant trans fatty acids to study the prevention of metabolic syndrome-a review.

Studies have reported the potential benefits of consuming conjugated linoleic acid (CLA) and ruminant trans fatty acids (R-TFAs) in reducing the risk factors of metabolic syndrome (MetS). In addition, encapsulation of CLA and R-TFAs may improve their oral delivery and further decrease the risk factors of MetS. The objectives of this review were (1) to discuss the advantages of encapsulation; (2) to compare the materials and techniques used for encapsulating CLA and R-TFAs; and (3) to review the effects of encapsulated vs non-encapsulated CLA and R-TFAs on MetS risk factors. Examination of papers citing micro- and nano-encapsulation methods used in food sciences, as well as the effects of encapsulated vs non-encapsulated CLA and R-TFAs, was conducted using the PubMed database. A total of 84 papers were examined; of these, 18 studies were selected that contained information on the effects of encapsulated CLA and R-TFAs. The 18 studies that described encapsulation of CLA or R-TFAs indicated that micro- or nano-encapsulation processes stabilized CLA and prevented oxidation. CLA was mainly encapsulated using carbohydrates or proteins. So far, oil-in-water emulsification followed by spray-drying were the frequently used techniques for encapsulation of CLA. Further, 4 studies investigated the effects of encapsulated CLA on MetS risk factors compared with non-encapsulated CLA. A limited number of studies investigated the encapsulation of R-TFAs. The effects of encapsulated CLA or R-TFAs on the risk factors for MetS remain understudied; thus, additional studies comparing the effects of encapsulated and non-encapsulated CLA or R-TFAs are needed.

Design of experiment and machine learning inform on the 3D printing of hydrogels for biomedical applications.

In the biomedical field, 3D printing has the potential to deliver on some of the promises of personalized therapy, notably by enabling point-of-care fabrication of medical devices, dosage forms and bioimplants. To achieve this full potential, a better understanding of the 3D printing processes is necessary, and non-destructive characterization methods must be developed. This study proposes methodologies to optimize the 3D printing parameters for soft material extrusion. We hypothesize that combining image processing with design of experiment (DoE) analyses and machine learning could help obtaining useful information from a quality-by-design perspective. Herein, we investigated the impact of three critical process parameters (printing speed, printing pressure and infill percentage) on three critical quality attributes (gel weight, total surface area and heterogeneity) monitored with a non-destructive methodology. DoE and machine learning were combined to obtain information on the process. This work paves the way for a rational approach to optimize 3D printing parameters in the biomedical field.

Size Exclusion of Radioactive Polymers (SERP) informs on the biodegradation of trimethyl chitosan and biodegradable polymer nanoparticles in vitro and in vivo.

Preparation of drug delivery systems and nanomedicines necessitates the use of biocompatible excipients that are readily eliminated from the body. The systematic preclinical development of novel materials requires tools to evaluate their pharmacokinetics, biodistribution and excretion. Herein, we propose a technique called Size Exclusion of Radioactive Polymers (SERP) to trail the disposition of a radiolabeled polymer and its nanoparticles using chromatography in the presence of complex biological media such as blood, urine and feces. Trimethyl chitosan (TMC) is a polysaccharide of natural origin showing promise for controlled and targeted drug delivery applications. SERP was used to monitor degradation of radiolabeled TMC and its nanoparticles in vitro in the presence of strong acid, enzymes released by macrophages, as well as in vivo after administration to rats. Excretion of the radiolabeled TMC nanoparticles in urine and feces was monitored for 14 days after dosing to healthy rats, confirming that the polymer could be readily eliminated from the body. This work demonstrates the ability of SERP to understand the biological journey of biomaterials in vivo. Paving the way to understand the fate of polymers and nanoparticles in complex environments, the technique might facilitate the development of safer and better tolerated nanomedicines.

Residual Solvents in Nanomedicine and Lipid-Based Drug Delivery Systems: a Case Study to Better Understand Processes.

PURPOSE: Complexities surrounding the manufacture and quality control of nanomedicines become increasingly apparent. This research article offers a case study to investigate how, at the laboratory scale, various stages of liposome and nanoparticle synthesis affect the amount of residual solvent found in the formulations. The objective is to bring insights on the reliability of each of these processes to provide final products which meet regulatory standards and facilitate identifying possible bottleneck early during the development process. METHODS: The residual solvent at various stages of preparation and purification was measured by headspace gas chromatography. Liposomes were prepared by two different methods with and without solvent. Polymer nanoparticles prepared via nanoprecipitation and purified by ultrafiltration were studied. The effects of purification by size exclusion chromatography and dialysis were also investigated. RESULTS: The complete removal of residual solvent requires processes which go beyond usual preparation methods. CONCLUSIONS: This work might prove valuable as a reference for scientists of different fields to compare their own practices and streamline the translation of nanomedicines into efficacious and safe drug products.

Improving oral bioavailability of acyclovir using nanoparticulates of thiolated xyloglucan.

Acyclovir a BCS class III drug exhibits poor bioavailability due to limited permeability. The intention of this research work was to formulate and characterize thiolated xyloglucan polysaccharide nanoparticles (TH-NPs) of acyclovir with the purpose of increasing its oral bioavailability. Acyclovir-loaded TH-NPs were prepared using a cross-linking agent. Interactions of formulation excipients were reconnoitered using Fourier transform infrared spectroscopy (FT-IR). The formulated nanoparticles were lyophilised by the addition of a cryoprotectant and characterized for its particle size, morphology and stability and optimized using Box Behnken Design.The optimized TH-NP formulation exhibited particle size of 474.4±2.01 and an entrapment efficiency of 81.57%. A marked enhancement in the mucoadhesion was also observed. In-vivo study in a rat model proved that relative bioavailability of acyclovir TH-NPs is ∼2.575 fold greater than that of the marketed acyclovir drug suspension.

Synthesis and characterization of a novel mucoadhesive derivative of xyloglucan.

A novel polymer in the form of a thiolated derivative of natural tamarind seed polysaccharide or xyloglucan was synthesized and its chacteristics as a mucoadhesive polymer were studied as a part of the study undertaken herein. The synthetic route followed involves a two-step reaction mechanism of firstly oxidizing xyloglucan and then further conjugating it with l-cysteine to form thiolated xyloglucan or thiomer via imine linkage. The thiomer thus formed was characterized using various analytical techniques as differential scanning calorimetry (DSC), X-ray diffraction analysis (XRD), and nuclear magnetic resonance (NMR). Ellman's method was used to determine the numbers of thiol groups/g of thiolated xyloglucan. Zeta potential measurements were carried out for thiolated xyloglucan. Viscosities of the formulated xyloglucan and thiolated xyloglucan gels were comparatively evaluated along with the evaluation of mucoadhesive properties of the gels using ex vivo bioadhesion study employing freshly excised sheep intestinal mucosa.