Bioactive and Physico-Chemical Assessment of Innovative Poly(lactic acid)-Based Biocomposites Containing Sage, Coconut Oil, and Modified Nanoclay.

The bioactivity of the versatile biodegradable biopolymer poly(lactic acid) (PLA) can be obtained by combining it with natural or synthetic compounds. This paper deals with the preparation of bioactive formulations involving the melt processing of PLA loaded with a medicinal plant (sage) and an edible oil (coconut oil), together with an organomodifed montmorillonite nanoclay, and an assessment of the resulting structural, surface, morphological, mechanical, and biological properties of the biocomposites. By modulating the components, the prepared biocomposites show flexibility, both antioxidant and antimicrobial activity, as well as a high degree of cytocompatibility, being capable to induce the cell adherence and proliferation on their surface. Overall, the obtained results suggest that the developed PLA-based biocomposites could potentially be used as bioactive materials in medical applications.

Assessment of the Antigenotoxic Activity of Poly(d,l-lactic- co-glycolic acid) Nanoparticles Loaded with Caffeic Acid Phenethyl Ester Using the Ames Salmonella/Microsome Assay.

In the present study, the antigenotoxic activity of poly(d,l-lactic- co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with caffeic acid phenethyl ester (CAPE) was investigated in comparison to free CAPE using the Ames Salmonella/microsome assay. Additionally, to elucidate the impacts of the type of solvent effect on antigenotoxic activity, the following systems were tested: CAPE in water (poor solvent), ethyl alcohol (good solvent), and PLGA NPs (unknown). The effect of the NP system on solubility was investigated for the first time by assessing the antigenotoxic potential. In this study, the CAPE/PLGA NPs were synthesized using an oil-in-water (o/w) single-emulsion solvent evaporation method with an average size of 206.2 ± 1.2 nm, ζ potential of -19.8 ± 2.5 mV, encapsulation efficiency of 87.2 ± 2.5%, and drug loading of 53.3 ± 1.8%. According to the results of the antigenotoxic activity, the highest antimutagenic activity in both applied strains was found for CAPE in ethanol, and the lowest activity was detected for CAPE in water. Our study has shown that NP systems exhibit high antigenotoxic activity, which is similar to the results of CAPE dissolved in ethanol. These results have shown that NP systems increase biological activity of hydrophobic substances by increasing their solubility and that the use of PLGA instead of organic solvents in drug production may provide an increase in their medical utility.

Direct assessment of renal mitochondrial redox state using hyperpolarized 13 C-acetoacetate.

PURPOSE: The purpose of this study was to investigate the hyperpolarized ketone body 13 C-acetoacetate (AcAc) and its conversion to 13 C-ß-hydroxybutyrate (ßOHB) in vivo, catalyzed by ß-hydroxybutyrate dehydrogenase (BDH), as a novel direct marker of mitochondrial redox state. METHODS: [1,3-13 C2 ]AcAc was synthesized by hydrolysis of the ethyl ester, and hyperpolarized via dissolution DNP. Cold storage under basic conditions resulted in sufficient chemical stability for use in hyperpolarized (HP) MRI studies. Polarizations and relaxation times of HP [1,3-13 C2 ]AcAc were measured in a clinical 3T MRI scanner, and 8 rats were scanned by dynamic HP 13 C MR spectroscopy of a slab through the kidneys. Four rats were scanned after acute treatment with high dose metformin (125 mg/kg, intravenous), which is known to modulate mitochondrial redox via inhibition of mitochondrial complex I. An additional metformin-treated rat was scanned by abdominal 2D CSI (8 mm × 8 mm). RESULTS: Polarizations of 7 ± 1% and 7 ± 3%, and T1 relaxation times of 58 ± 5 s and 52 ± 3 s, were attained at the C1 and C3 positions, respectively. Rapid conversion of HP AcAc to ßOHB was detected in rat kidney in vivo, via the C1 label. The product HP ßOHB was resolved from closely resonating acetate. Conversion to ßOHB was also detected via 2D CSI, in both kidney as well as liver regions. Metformin treatment resulted in a significant increase (40%, P = 0.01) of conversion of HP AcAc to ßOHB. CONCLUSION: Rapid conversion of HP AcAc to ßOHB was observed in rat kidney in vivo and is a promising new non-invasive marker of mitochondrial redox state. Magn Reson Med 79:1862-1869, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Development of PLGA nanoparticles loaded with clofazimine for oral delivery: Assessment of formulation variables and intestinal permeability.

The use of polymeric nanoparticles as delivery systems is a promising tool to overcome drawbacks related to low aqueous solubility of drugs, which limit their in vivo bioavailability. The aim of this study was to decrease clofazimine (CLZ) toxicity using experimental design to formulate CLZ loaded in PLGA nanoparticles (NPs-CLZ) through a Plackett-Burman design (PBD). A screening PBD was constructed with twelve formulations involving six variables among process and formulation parameters and the selected responses were particle size, polydispersity index (PDI), association efficiency (AE) and drug loading (DL). The formulation was achieved based on the desirability tool, and the obtained NPs-CLZ formulation was characterized regarding morphology, physicochemical properties, in vitro release and cellular studies. Particle size, PDI, AE and DL were found to be 211±3nm, 0.211±0.009, 70±5% and 12±1%, respectively. Physicochemical studies confirmed the absence of chemical interactions between CLZ and other nanoparticles constituents and the amorphous state of CLZ, while morphological analysis revealed the spherical shape of the particles. In vitro release profile of CLZ from NPs-PLGA showed a slow pattern of drug release. Cell viability studies towards intestinal cells revealed that NPs-CLZ did not show CLZ toxicity on Caco-2 and HT29-MTX cells compared to free CLZ solutions. Moreover, CLZ could permeate Caco-2 monolayers substantially at the end of 8h. It can be concluded that the proposed NPs-CLZ represent a promising platform to the oral delivery of CLZ as they were able to decrease its intrinsic toxicity, with improved absorption.

In vitro and in vivo assessment of lactic acid-modified chitosan scaffolds for potential treatment of full-thickness burns.

Autologous skin transplantation is today's "gold standard" treatment for full-thickness burns. However, when > 30% of total body surface area is damaged, there is an important shortage of autologous donor sites for skin grafting; then, treatment alternatives become crucial. Such alternatives can be based on polymeric scaffolds capable of functioning as protective covers and cells/factors carriers. Chitosan (CTS) is a natural-derived polymer with relevant biological-related properties but poor mechanical performance. Improved mechanical properties can be achieved through lactic acid grafting (LA-g); nevertheless, LA-g affects the biological response towards the CTS-based materials. In this work, CTS-LA scaffolds with different LA-g percentages were synthesized and evaluated to determine appropriate LA-g degrees for full-thickness burns treatment. In vitro results indicated that the higher the LA-g percentage, the lower the capability of the scaffolds to sustain fibroblasts culture. Scaffolds with LA-g around 28% (CTS-LA28) sustained cell culture and allowed normal cell functionality. Further evaluation of CTS-LA28 as acellular and cellular grafts in a full-thickness burn mouse model showed that at 28 days post-burn, macroscopic characteristic of the reparation tissue were closer to healthy skin when cellular grafts were used for treatment; histological evaluation also showed that dermis cellularity and collagenous fibers structure were similar to those in healthy skin when cellular grafts were used for burns treatment. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2875-2891, 2017.

Assessment of Adhesion and Proliferation of Bone Marrow Mesenchymal Stem Cells in Polymer Matrices with rhGH.

PURPOSE: Biomaterials, as an alternative to autogenous bone and other biologic tissues, have been widely used in oral and maxillofacial surgery. In this context, a biomaterial that functions as a scaffold (osteoconductor), combined with a growth factor (osteoinductor), would be of great interest for clinical application. Biodegradable polymers used for slow drug release have been investigated, demonstrating good results and interesting potential. Growth hormone (GH) may be released by incorporating it into these polymers. This study aimed to evaluate cell adhesion and proliferation of a polymeric biomaterial for slow release of recombinant human GH (rhGH). MATERIALS AND METHODS: Poly(lactic-co-glycolic acid) (PLGA) and PLGA/polycaprolactone (PCL) (at a 70/30 ratio of PLGA to PCL) matrices were prepared by the solvent evaporation method, combined or not with GH. Biomaterials were tested for cell adhesion and proliferation by culture in mesenchymal stem cells derived from Wistar rat bone marrow, 4',6-diamidino-2-phenylindole (DAPI) staining, and subsequent cell counting, in addition to scanning electron microscopy. Cell adhesion and proliferation was assessed at 24 and 72 hours of biomaterial exposure to culture medium. RESULTS: All tested polymers exhibited cell adhesion and proliferation. However, PLGA-based biomaterials, especially when combined with GH, showed greater cell proliferation when the difference in growth from 24 to 72 hours was evaluated. GH appeared to modify the polymer surface, with increased roughness and microporosity. This feature was more evident in the PLGA + GH combination. CONCLUSION: The biomaterials tested showed pronounced cell adhesion in all test groups, and GH appeared to contribute to the increase in cell proliferation, especially when combined with PLGA as compared with pure PLGA. Further studies are required to clarify this potential for development of new biomaterials.

Assessment of penetration potential of pH responsive double walled biodegradable nanogels coated with eucalyptus oil for the controlled delivery of 5-fluorouracil: In vitro and ex vivo studies.

Penetration enhancers coated biodegradable polymeric nanogels loaded with cytotoxic drugs applied via the topical route, can be a promising strategy for improving the chemotherapeutic efficiency of skin cancers. The major objective of proposed research was to investigate the in vitro and ex vivo chemotherapeutic potential of double walled PLGA-chitosan biodegradable nanogel entrapped with 5-fluororuacil (5-FU) coated with eucalyptus oil, topically applied onto the skin. 5-FU was first entrapped in PLGA core by solvent evaporation technique followed by coating with cationic chitosan for ionic interaction with anionic skin cancer cell membrane. A surface coating of eucalyptus oil (1%) was employed to improve the penetration efficacy of the nanogel into stratum corneum. The surface modified biodegradable double walled nanogel was characterized for particle size, charge and thermal properties followed by pH dependent in vitro analysis. Human keratinocyte (HaCaT) cell line was employed for the bio- and cyto-compatibility testing prior to the hemolysis assay and coagulation assessment. A porcine skin ex vivo screening was performed for assessing the penetration potential of the nanogels. DLS and TEM revealed a particle size about 170nm for the double walled nanogels. The nanogels also exhibited high thermal stability as analyzed by thermogravimetry (TG) and differential thermal analysis (DTA). The drug entrapment efficacy was about ~40%. The drug release showed sustained release pattern noted up to 24h. The low hemolysis of 2.39% with short prothrombin time (PT) and activated partial thromboplastin time (APTT) of 14.2 and 35.5s respectively, revealed high biocompatibility of the nanogels. The cellular uptake and localization was assessed by confocal microscopy. The cytotoxicity (MTT assay) on HaCaT cell line demonstrated high cytocompatibilty of the nanogels. An ex vivo evaluation using porcine skin displayed efficient and steady state flux of 5-FU from the biodegradable nanogles into the skin, while the histology of the porcine skin revealed enhanced penetration potential of eucalyptus oil coated PLGA-chitosan double walled nanogels. Taken together the in vivo and ex vivo results portend promising potential for the utility of the biodegradable nanogels for treating skin cancers.

Toxicity assessment and feasible recycling process for amorphous silicon and CIS waste photovoltaic panels.

End-of-Life (EoL) photovoltaic (P/V) modules, which are recently included in the 2012/19/EU recast, require sound and sustainable treatment. Under this perspective, this paper deals with 2nd generation P/V waste modules, known as thin-film, via applying chemical treatment techniques. Two different types of modules are examined: (i) tandem a-Si:H/µc-Si:H panel and, (ii) Copper-Indium-Selenide (CIS) panel. Panels' pretreatment includes collection, manual dismantling and shredding; pulverization and digestion are further conducted to identify their chemical composition. A variety of elements is determined in the samples leachates' after both microwave-assisted total digestion and Toxicity Characteristic Leaching Procedure (TCLP test) using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) analysis. The analysis reveals that several elements are detected in the two of panels, with no sample exceeds the TCLP test. Concentrations of precious and critical metals are also measured, which generates great incentives for recovery. Then, further experiments, for P/V recycling investigation, are presented using different acids or acid mixtures under a variety of temperatures and a stable S/L ratio, with or without agitation, in order to determine the optimal recycling conditions. The results verify that chemical treatment in P/V shredded samples is efficient since driving to ethylene-vinyl acetate (EVA) resin's dissolution, as well as valuable structural materials recovery (P/V glass, ribbons, cells, P/V intermediate layers). Among the solvents used, sulfuric acid and lactic acid demonstrate the most efficient and strongest performance on panels' treatment at gentle temperatures providing favorably low energy requirements.

Development and in vivo safety assessment of tenofovir-loaded nanoparticles-in-film as a novel vaginal microbicide delivery system.

UNLABELLED: Topical pre-exposure prophylaxis (PrEP) with antiretroviral drugs holds promise in preventing vaginal transmission of HIV. However, significant biomedical and social issues found in multiple past clinical trials still need to be addressed in order to optimize protection and users' adherence. One approach may be the development of improved microbicide products. A novel delivery platform comprising drug-loaded nanoparticles (NPs) incorporated into a thin polymeric film base (NPs-in-film) was developed in order to allow the vaginal administration of the microbicide drug candidate tenofovir. The system was optimized for relevant physicochemical features and characterized for biological properties, namely cytotoxicity and safety in a mouse model. Tenofovir-loaded poly(lactic-co-glycolic acid) (PLGA)/stearylamine (SA) composite NPs with mean diameter of 127nm were obtained with drug association efficiency above 50%, and further incorporated into an approximately 115µm thick, hydroxypropyl methylcellulose/poly(vinyl alcohol)-based film. The system was shown to possess suitable mechanical properties for vaginal administration and to quickly disintegrate in approximately 9min upon contact with a simulated vaginal fluid (SVF). The original osmolarity and pH of SVF was not affected by the film. Tenofovir was also released in a biphasic fashion (around 30% of the drug in 15min, followed by sustained release up to 24h). The incorporation of NPs further improved the adhesive potential of the film to ex vivo pig vaginal mucosa. Cytotoxicity of NPs and film was significantly increased by the incorporation of SA, but remained at levels considered tolerable for vaginal delivery of tenofovir. Moreover, histological analysis of genital tissues and cytokine/chemokine levels in vaginal lavages upon 14days of daily vaginal administration to mice confirmed that tenofovir-loaded NPs-in-film was safe and did not induce any apparent histological changes or pro-inflammatory response. Overall, obtained data support that the proposed delivery system combining the use of polymeric NPs and a film base may constitute an exciting alternative for the vaginal administration of microbicide drugs in the context of topical PrEP. STATEMENT OF SIGNIFICANCE: The development of nanotechnology-based microbicides is a recent but promising research field seeking for new strategies to circumvent HIV sexual transmission. Different reports detail on the multiple potential advantages of using drug nanocarriers for such purpose. However, one important issue being frequently neglected regards the development of vehicles for the administration of microbicide nanosystems. In this study, we propose and detail on the development of a nanoparticle-in-film system for the vaginal delivery of the microbicide drug candidate tenofovir. This is an innovative approach that, to our best knowledge, had never been tested for tenofovir. Results, including those from in vivo testing, sustain that the proposed system is safe and holds potential for further development as a vaginal microbicide product.

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles.

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules.

Microencapsulation of rifampicin for the prevention of endophthalmitis: In vitro release studies and antibacterial assessment.

Rifampicin encapsulated microparticles were designed for intraocular injection after cataract surgery to prevent postoperative endophthalmitis. Microparticles were formulated by emulsification diffusion method using poly(lactic acid-co-glycolic acid) (PLGA) as polymer in order to propose a new form of rifampicin that overcome its limitations in intraocular delivery. Depending on processing formulation, different types of microparticles were prepared, characterized and evaluated by in vitro release studies. Two types of microparticles were selected to get a burst release of rifampicin, to reach minimal inhibitory concentrations to inhibit 90% of Staphylococcus epidermidis mainly involved in postoperative endophthalmitis, combined with a sustained release to maintain rifampicin concentration over 24h. The antibacterial activity and antiadhesive property on intraocular lenses were evaluated on S. epidermidis. Microparticles, with a rapid rifampicin release profile, showed an effect towards bacteria development similar to free rifampicin over 48h. However, slow-release profile microparticles exhibited a similar antibacterial effect during the first 24h, and were able to destroy all the S epidermidis in the medium after 30h. The association of the two formulations allowed obtaining interesting antibacterial profile. Moreover, rifampicin-loaded microparticles have shown a very efficient anti-adherent effect of S. epidermidis on intraocular lenses at 24h. These results propose rifampicin microparticles as suitable for antibioprophylaxis of the postoperative endophthalmitis.

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

CONTEXT: The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. OBJECTIVE: To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. METHODS: Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. RESULTS: The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. CONCLUSION: This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro, ex vivo and cytocompatibility assessment.

In the present study we investigated polymer-lipid microparticles loaded with ropinirole hydrochloride (RH) for nasal delivery. RH microparticles were further evaluated by means of scanning electron microscopy (SEM), ζ-potential measurements, Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD). In vitro release studies were performed in simulated nasal electrolyte solution (SNES) pH5.5 at 35°C. Ex vivo permeation studies were conducted across sheep nasal mucosa. Cytocompatibility was tested in cultured human airway epithelial cells (Calu-3). SEM studies revealed spheroid microparticles in the range of 2.09µm to 2.41µm. The presence of trimethylchitosan (TMC) induced a slight shift towards less negative ζ-potential values. Surface chemistry (XPS) revealed the presence of dipalmitoylphospatidylcholine (DPPC) and poly(lactic-co-glycolic acid) (PLGA) onto microparticles' surface, further corroborating the FT-IR and XRD findings. In vitro release studies showed that the microparticle composition can partly modulate the release of RH. Ex vivo studies demonstrated a 2.35-folded enhancement of RH permeation when RH was co-formulated with TMC of low molecular weight, compared to the control. All formulations tested were found to be non-toxic to cells. The results suggest that polymer-lipid microparticles may be a promising carrier for the nasal delivery of RH.

Mechanical tension applied to substrate films specifies location of neuritogenesis and promotes major neurite growth at the expense of minor neurite development.

One obstacle in neural repair is facilitating axon growth long enough to reach denervated targets. Recent studies show that axonal growth is accelerated by applying tension to bundles of neurites, and additional studies show that mechanical tension is critical to all neurite growth. However, no studies yet describe how individual neurons respond to tensile forces applied to cell bodies and neurites simultaneously; neither do any test motor neurons, a phenotype critical to neural repair. Here we examine the growth of dissociated motor neurons on stretchable substrates. E15 spinal motor neurons were cultured on poly-lactide-co-glycolide films stretched at 4.8, 9.6, or 14.3 mm day(-1). Morphological analysis revealed that substrate stretching has profound effects on developing motor neurons. Stretching increases major neurite length; it also forces neuritogenesis to occur nearest poles of the cell closest to the sources of tension. Stretching also reduces the number of neurites per neuron. These data show that substrate stretching affects neuronal morphology by specifying locations on the cell where neuritogenesis occurs and favoring major neurite growth at the expense of minor neurites. These results serve as a building block for development of new techniques to control and improve the growth of neurons for nerve repair purposes.

In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors.

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-ß3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors.

Experimental Investigation and Thermodynamic Assessment of Phase Equilibria in the PLLA/Dioxane/Water Ternary System for Applications in the Biomedical Field.

Fundamental understanding of thermodynamic of phase separation plays a key role in tuning the desired features of biomedical devices. In particular, phase separation of ternary solution is of remarkable interest in processes to obtain biodegradable and biocompatible architectures applied as artificial devices to repair, replace, or support damaged tissues or organs. In these perspectives, thermally induced phase separation (TIPS) is the most widely used technique to obtained porous morphologies and, in addition, among different ternary systems, polylactic acid (PLLA)/dioxane/water has given promising results and has been largely studied. However, to increase the control of TIPS-based processes and architectures, an investigation of the basic energetic phenomena occurring during phase separation is still required. Here we propose an experimental investigation of the selected ternary system by using isothermal titration calorimetric approach at different solvent/antisolvent ratio and a thermodynamic explanation related to the polymer-solvents interactions in terms of energetic contribution to the phase separation process. Furthermore, relevant information about the phase diagrams and interaction parameters of the studied systems are furnished in terms of liquid-liquid miscibility gap. Indeed, polymer-solvents interactions are responsible for the mechanism of the phase separation process and, therefore, of the final features of the morphologies; the knowledge of such data is fundamental to control processes for the production of membranes, scaffolds and several nanostructures. The behavior of the polymer at different solvent/nonsolvent ratios is discussed in terms of solvation mechanism and a preliminary contribution to the understanding of the role of the hydrogen bonding in the interface phenomena is also reported. It is the first time that thermodynamic data of a ternary system are collected by mean of nano-isothermal titration calorimetry (nano-ITC). Supporting Information is available.

High titer L-lactic acid production from corn stover with minimum wastewater generation and techno-economic evaluation based on Aspen plus modeling.

Technological potentials of l-lactic acid production from corn stover feedstock were investigated by experimental and techno-economic studies. An optimal performance with 104.5 g/L in l-lactic acid titer and 71.5% in overall yield from cellulose in corn stover to l-lactic acid using an engineered Pediococcus acidilactici strain were obtained by overcoming several technical barriers. A rigorous Aspen plus model for l-lactic acid production starting from dry dilute acid pretreated and biodetoxified corn stover was developed. The techno-economic analysis shows that the minimum l-lactic acid selling price (MLSP) was $0.523 per kg, which was close to that of the commercial l-lactic acid produced from starch feedstock, and 24% less expensive than that of ethanol from corn stover, even though the xylose utilization was not considered. The study provided a prototype of industrial application and an evaluation model for high titer l-lactic acid production from lignocellulose feedstock.

SN-38 active loading in poly(lactic-co-glycolic acid) nanoparticles and assessment of their anticancer properties on COLO-205 human colon adenocarcinoma cells.

SN-38 is a highly effective drug against many cancers. The development of an optimal delivery system for SN-38 is extremely challenging due to its low solubility and labile lactone ring. Herein, SN-38 encapsulated in poly(D,L-lactide-co-glycolide) nanoparticles (NPs) is introduced to enhance its solubility, stability and cellular uptake. SN-38-loaded NPs prepared by spontaneous emulsification solvent diffusion (SESD) method had an average diameter of 310 nm, a zeta potential of -9.69 mV and a loading efficiency of 71%. They were able to protect the active lactone ring of SN-38 against inactivation under physiological condition. A colorectal adenocarcinoma cell line (COLO-205) was used to assess the NPs effects on cytotoxicity and cellular uptake. Result showed a significant decreased cell proliferation and cell apoptosis. These results suggest that these SN-38-loaded NPs can be an effective delivery system for the treatment of colon cancer and potentially for other types of cancers.

Identification and Assessment of Octreotide Acylation in Polyester Microspheres by LC-MS/MS.

PURPOSE: Polyesters with hydrophilic domains, i.e., poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(L-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic matrices. Our purpose is to assess the extent and sites of acylation of octreotide loaded in microspheres using tandem mass spectrometry analysis. METHODS: Octreotide loaded microspheres were prepared by a double emulsion solvent evaporation technique. Release profiles of octreotide from hydrophilic microspheres were compared with that of PLGA microspheres. To scrutinize the structural information and localize the actual modification site(s) of octreotide, liquid chromatography ion-trap mass spectrometry (LC-ITMS) was performed on the acylated adducts. RESULTS: Hydrophilic microspheres showed less acylated adducts in comparison with PLGA microspheres. LC-MS/MS showed that besides the N-terminus and primary amine of lysine, the primary hydroxyl of the end group of octreotide was also subjected to acylation. Nucleophilic attack of the peptide can also occur to the carbamate bond presented in (PC-PEG-PC)-(PL) since 1,4-butanediisocyanate was used as the chain extender. CONCLUSIONS: Hydrophilic polyesters are promising systems for controlled release of peptide because substantially less acylation occurs in microspheres based on these polymers. LC-ITMS provided detailed structural information of octreotide modifications via mass analysis of ion fragments.