Polyester Nanocapsules for Intravenous Delivery of Artemether: Formulation Development, Antimalarial Efficacy, and Cardioprotective Effects In Vivo.

Artemether (ATM) is an effective antimalarial drug that also has a short half-life in the blood. Furthermore, ATM is also cardiotoxic and is associated with pro-arrhythmogenic risks. We aimed to develop a delivery system enabling the prolonged release of ATM into the blood coupled with reduced cardiotoxicity. To achieve this, we prepared polymeric nanocapsules (NCs) from different biodegradable polyesters, namely poly(D,L-lactide) (PLA), poly-ε-caprolactone (PCL), and surface-modified NCs, using a monomethoxi-polyethylene glycol-block-poly(D,L-lactide) (PEG5kDa-PLA45kDa) polymer. Using this approach, we were able to encapsulate high yields of ATM (>85%, 0−4 mg/mL) within the oily core of the NCs. The PCL-NCs exhibited the highest percentage of ATM loading as well as a slow release rate. Atomic force microscopy showed nanometric and spherical particles with a narrow size dispersion. We used the PCL NCs loaded with ATM for biological evaluation following IV administration. As with free-ATM, the ATM-PCL-NCs formulation exhibited potent antimalarial efficacy using either the "Four-day test" protocol (ATM total at the end of the 4 daily doses: 40 and 80 mg/kg) in Swiss mice infected with P. berghei or a single low dose (20 mg/kg) of ATM in mice with higher parasitemia (15%). In healthy rats, IV administration of single doses of free-ATM (40 or 80 mg/kg) prolonged cardiac QT and QTc intervals and induced both bradycardia and hypotension. Repeated IV administration of free-ATM (four IV doses at 20 mg/kg every 12 h for 48 h) also prolonged the QT and QTc intervals but, paradoxically, induced tachycardia and hypertension. Remarkably, the incorporation of ATM in ATM-PCL-NCs reduced all adverse effects. In conclusion, the encapsulation of ATM in biodegradable polyester NCs reduces its cardiovascular toxicity without affecting its antimalarial efficacy.

Preparation, Characterization and Evaluation of Antibacterial Properties of Polylactide-Polyethylene Glycol-Chitosan Active Composite Films.

Chitin is a natural biopolymer obtained from the exoskeleton of crustaceans. Chitosan is a derivative of chitin, which has antimicrobial properties and potential applications in several industries. Moreover, the composites of chitosan with other biodegradable polymers, such as polylactide (PLA) as packaging film, have shown promising results. In this study, chitosan was obtained and characterized from shrimp shells. Then, polylactide-chitosan composite films were prepared by a solvent casting technique using various amounts of chitosan (0.5-2% w/w) and polyethylene glycol as plasticizer (10% w/w). Thermal, mechanical properties, Fourier-transform infrared, scanning electron microscopy, as well as antibacterial properties of composite films were determined. It was found that adding chitosan (CH) into PLA films has a significant effect on tensile strength and no effect on thermal properties. The results showed a reduction on average of 1 log of colony-forming units against Staphylococcus aureus, while there is no antibacterial effect against Salmonella typhimurium. The study proved the antibacterial effect of CH in films of PLA against Gram-positive bacteria and appropriate mechanical properties. These films could be used for the development of biodegradable/eco-friendly food packaging prototypes, as a potential solution to replace conventional non-degradable packaging materials.

Long-Term Evaluation of Poly(lactic acid) (PLA) Implants in a Horse: An Experimental Pilot Study.

In horses, there is an increasing interest in developing long-lasting drug formulations, with biopolymers as viable carrier alternatives in addition to their use as scaffolds, suture threads, screws, pins, and plates for orthopedic surgeries. This communication focuses on the prolonged biocompatibility and biodegradation of PLA, prepared by hot pressing at 180 °C. Six samples were implanted subcutaneously on the lateral surface of the neck of one horse. The polymers remained implanted for 24 to 57 weeks. Physical examination, plasma fibrinogen, and the mechanical nociceptive threshold (MNT) were performed. After 24, 28, 34, 38, and 57 weeks, the materials were removed for histochemical analysis using hematoxylin-eosin and scanning electron microscopy (SEM). There were no essential clinical changes. MNT decreased after the implantation procedure, returning to normal after 48 h. A foreign body response was observed by histopathologic evaluation up to 38 weeks. At 57 weeks, no polymer or fibrotic capsules were identified. SEM showed surface roughness suggesting a biodegradation process, with an increase in the median pore diameter. As in the histopathological evaluation, it was not possible to detect the polymer 57 weeks after implantation. PLA showed biocompatible degradation and these findings may contribute to future research in the biomedical area.

Food packaging wastes amid the COVID-19 pandemic: Trends and challenges.

BACKGROUND: The COVID-19 crisis generated changes in consumer behavior related to food purchase and the management of food packaging. Due to the intensification of online purchases for home delivery, there has been an increase in the use of food packaging (mostly non-biodegradable or non-renewable). Moreover, the fear of contamination with SARS-CoV-2 through contact with materials and surfaces has led to an intensified disposal of food packaging, promoting a setback in waste management. SCOPE AND APPROACH: The purpose of this short commentary is to address the impacts of increased use and disposal of food packaging during the COVID-19 pandemic. Technological solutions have been presented as tools to minimize the environmental impacts of the increased volume of disposed food packaging (namely, the development of biodegradable food packaging) as well as to minimize the occurrence of cross-contamination (namely, the incorporation of active antiviral components). KEY FINDINGS AND CONCLUSIONS: The consumer behavior in the COVID-19 pandemic requires actions concerning adoption of bioplastics for single-use food packaging. Polylactide (PLA) stands out for high production viability, performance comparable to those of petroleum-based thermoplastics, and carbon neutral life cycle. Moreover, active components including organic compounds (resveratrol, luteolin, myricetin etc.) and metals (e.g., copper, zinc, silver) can mitigate cross-contamination. Therefore, there are opportunities to reduce food packaging-related environmental footprints while also decreasing the occurrence of surface-mediated cross-contamination.

Preparation and in vitro release profiling of PLGA microspheres containing BSA as a model protein

Conventional drug formulations are incapable of adequate delivery of proteins and peptides for therapeutic purposes. As these molecules have very short biological half-life, multiple dosing is required to achieve the desirable therapeutic effects. Microspheres are able to encapsulate proteins and peptide in the polymeric matrix while protecting them from enzymatic degradation. In this study Bovine Serum Albumin (BSA) matrix type microspheres were fabricated using Polylactide-co-glycolide (PLGA) by double emulsion solvent evaporation method. The effects of variables such as homogenizer speed, molecular weight of polymer and the effect of pH of the water phases, were investigated against factors such as drug loading, encapsulation efficiency, morphology, size, drug distribution and release profile of the microspheres. Results, suggested that an increase in homogenization speed leads to a decrease in microsphere size. The increase in homogenization speed also caused a significant effect on the release profile only when higher molecular weight of polymer had been used.. The pH change of the internal aqueous phase led to modification of surface morphology of spheres to a porous structure that significantly increased the total amount of released protein. Integrity of protein structure was intact as shown by SDS-PAGE. According to the results, it can be concluded that we achieved a reproducible method regarding controlled protein delivery for different sizes of particles.

Effect of Different Tensoactives on the Morphology and Release Kinetics of PLA-b-PEG Microcapsules Loaded With the Natural Anticancer Compound Perillyl Alcohol.

Perillyl alcohol is a natural compound that has attracted a significant interest due to its potent antitumor activity. However, clinical trials have exhibited poor tolerance by oral administration, mainly due to gastrointestinal side effects. We propose the entrapment of perillyl alcohol into poly(D,L-lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG) as delivery platform (entrapment efficiency of 63%-68%). The influence of different concentrations of the tensoactives poly(vinyl alcohol) and sodium cholate (SC) on shear strength and morphology was evaluated by confocal laser scanning microscopy and interfacial tension studies. Only the microcapsules formulated with SC maintained their sphericity when submitted to shear stress. These results indicate that the interface is better organized with SC, conferring mutual stacked packing that is able to better stabilize the organic drop. The in vitro release profile of the drug from the microcapsules was correlated with pore formation and polymer degradation, best fitted to the Baker-Lonsdale model. The loaded microcapsules showed an IC50 equivalent to that of the free drug (80 µg/mL) after 72 h of exposure. However, after 24 h of exposure, loaded microcapsules showed an IC50 almost two-fold higher (220 µg/mL) suggesting gradual release.

Mechanisms of interaction of biodegradable polyester nanocapsules with non-phagocytic cells.

The interaction of polymer nanocapsules (NC) prepared from four biodegradable polyesters with variable polymer hydrophobicity (PCL, PLA, PLGA and PLA-PEG) was investigated in the non-phagocytic Vero, Caco-2 and HepG2 cell lines. The NC, labeled with the highly lipophilic fluorescent indocarbocyanine dye DIL, had very similar sizes (approx. 140 nm) and negative zeta-potentials. Asymmetric flow field-flow fractionation evidenced NC colloidal stability and negligible transfer of the dye to serum proteins in the incubation medium. The cytotoxicity of the NC was evaluated via MTT assay over a large polymer concentration range (1-1000 µg/mL) and time of exposure (2, 24 and 48 h). The NC were safe in vitro up to a concentration of approx. 100 µg/mL or higher, depending on the cell line and nature of the polymer. Vero cells were more sensitive to the NC, in particular NC of the more hydrophobic polymer. The cells were exposed to endocytosis inhibitors, incubated with NC, and the cell-associated fluorescence was quantified by spectrofluorometry. HepG2 cells presented a 1.5-2-fold higher endocytic capacity than Caco-2 and Vero cells. The main mechanism of NC uptake was caveolin-mediated endocytosis in HepG2 and Vero cells, and macropinocytosis in Caco-2 cells. Polymer hydrophobicity had an effect on the level of NC associated to HepG2 cells and to a lesser extent on the endocytosis mechanisms in Vero and Caco-2 cells. The NC uptake levels and endocytosis mechanisms differed significantly between cell lines tested.

Bulk Modification of Poly(lactide) (PLA) via Copolymerization with Poly(propylene glycol) Diglycidylether (PPGDGE).

Copolymers of l-lactide and poly(propylene glycol) diglycidyl ether (PPGDGE380) were synthesized by ring opening polymerization (ROP). Stannous octoate was used as the catalyst and 1-dodecanol as the initiator. The effect of the variables on the thermal properties of the copolymers was investigated by differential scanning calorimetry (DSC). Contact angle measurements were made in order to study the wettability of the synthesized copolymers. The copolymers differed widely in their physical characteristics, ranging from weak elastomers to tougher thermoplastics, according to the ratio of l-lactide and PPGDGE380. The results showed that the copolymers were more hydrophilic than neat Poly(lactide) (PLA) and the monomer ratio had a strong influence on the hydrophilic properties.

Porous Bioactive Nanofibers via Cryogenic Solution Blow Spinning and Their Formation into 3D Macroporous Scaffolds.

There is increasing focus on the development of bioactive scaffolds for tissue engineering and regenerative medicine that mimic the native nanofibrillar extracellular matrix. Solution blow spinning (SBS) is a rapid, simple technique that produces nanofibers with open fiber networks for enhanced cell infiltration. In this work, highly porous bioactive fibers were produced by combining SBS with thermally induced phase separation. Fibers composed of poly(d,l-lactide) (PLA) and dimethyl carbonate were sprayed directly into a cryogenic environment and subsequently lyophilized, rendering them highly porous. The surface areas of the porous fibers were an order of magnitude higher in comparison with smooth control fibers of the same diameter (43.5 m2·g-1 for porous fibers produced from 15% w/v PLA in dimethyl carbonate) and exhibited elongated surface pores. Macroporous scaffolds were produced by spraying water droplets simultaneously with fiber formation, creating a network of fibers and ice microspheres, which act as in situ macroporosifiers. Subsequent lyophilization resulted in three-dimensional (3D) scaffolds formed of porous nanofibers with interconnected macropores due to the presence of the ice spheres. Nanobioactive glass was incorporated for the production of 3D macroporous, bioactive, therapeutic-ion-releasing scaffolds with potential applications in non-load-bearing bone tissue engineering. The bioactive characteristics of the fibers were assessed in vitro through immersion in simulated body fluid. The release of soluble silica ions was faster for the porous fibers within the first 24 h, with confirmation of hydroxyapatite on the fiber surface within 84 h.