Molecular Weight Grades Research Articles

Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model.

Inflammatory bowel disease (IBD) affects over 7 million people worldwide and significant side effects are associated with current therapies such as tofacitinib citrate (TFC), which is linked to increased risks of malignancy and congestive heart issues. To mitigate these systemic adverse effects, localised drug delivery via nano-sized carriers to inflamed gut tissues represents a promising approach. Herein, we aimed to optimise the synthesis of nanoparticles (NPs) using a low molecular weight grade of Poly(lactic-co-glycolic acid) (PLGA) 50:50 loaded with TFC. This approach leverages the dual anti-inflammatory action of TFC and the local production of anti-inflammatory short-chain fatty acids from the degradation of PLGA by colonic gut microbiota. NPs were produced by nanoprecipitation and characterised for their drug release profile in vitro. The efficacy of the enhanced PLGA-TFC NPs was then tested in a C57BL/6 DSS colitis mouse model. The release profile of TFC from the enhanced PLGA NPs showed a 40% burst release within the first hour, followed by up to 80% drug release in the colonic environment. Notably, the degradation of PLGA by colonic gut microbiota did not significantly influence TFC release. In the mouse model, neither PLGA NPs alone nor TFC alone showed significant effects on weight loss compared to the TFC-loaded PLGA NPs, emphasising the enhanced efficacy potential of the combined formulation. Altogether, these results suggest a promising role of NP delivery systems in enhancing TFC efficacy, marking a significant step towards reducing dosage and associated side effects in IBD treatment. This study underscores the potential of PLGA-TFC NPs in providing targeted and effective therapy for IBD.

Dissolution mechanisms of amorphous solid dispersions: Role of polymer molecular weight and identification of a new failure mode

The mechanisms of drug release from amorphous solid dispersions (ASDs) are complex and not fully explored, making it difficult to optimize for in vivo performance. A recurring behavior has been the limit of congruency (LoC), a drug loading above which the ASD surface forms an amorphous drug-rich barrier in the presence of water, which hinders release, especially in non-sink conditions. Drug-polymer interactions and drug glass transition temperature were reported to affect the LoC. However, the effect of polymer molecular weight has not been explored. ASDs of clotrimazole and different molecular weight grades of PVP were studied for their release to obtain their LoC drug loadings. Failure modes underpinning the LoC were investigated using fluorescence confocal microscopy to analyze the ASD/solution interface and phase behavior of ASD films at high relative humidity. ASDs with good release formed stable drug-rich nanodroplets at the ASD/solution interface, while ASDs with poor release were limited by one of two failure modes, depending on PVP molecular weight. In Failure Mode I the nanodroplets quickly agglomerated, while in Failure Mode II the system underwent phase inversion. This work highlights the importance of identifying the mechanisms underlying the LoC to improve the release of higher drug loading ASDs.

Temperature-sensitive fragrance-releasing polymeric microcapsules

This research aimed to control release of fragrance using thermally-actuated microcapsules so that the release rate shows a considerable change at a certain temperature. Accordingly, four different polymers, namely, two grades of poly(methyl methacrylate) having different molecular weight as well as two poly[(methyl methacrylate)–co-(2-ethylhexyl acrylate)] copolymers, which were synthesized in this work, were designated as capsules’ shell. Number-average molecular weight of the copolymers and one of the two used PMMA grades was in the range of 47 to 56 kDa while that of the other PMMA grade was 344 kDa. Furthermore, Tg of the lower molecular weight grade PMMA and the two copolymers was determined as 119.3, 72.2 and 66.3 °C, respectively, using DSC experiments. Subsequently, R-Limonene as a model fragrance, was encapsulated by either of the polymers using solvent evaporation method. Effect of various parameters, including molecular weight and Tg of the shell polymer and concentration of emulsifier, on morphological characteristics of the microcapsules were investigated. Using two microscopic techniques, it was observed that increment of molecular weight of shell polymer enhances microcapsules’ size, shell thickness and porosity. Moreover, elevation of emulsifier concentration to a certain value of 1.5 wt% was shown to lessen size and porosity of microcapsules. The fragrance release profiles were determined and fitted to several mathematical models, proving that at least one more mechanism, in addition to diffusion, is involved in the release, which was attributed to capillary effects in the shell pores. Moreover, a pronounced increase in release rate upon elevation of temperature from 5 to 15 °C was observed for either of the copolymer shells. The effect was ascribed to remarkable strengthening of segmental mobility of the copolymers due to elevation of temperature and can be regarded as a promising way for the fabrication of smart microcapsules capable of thermal controlling fragrance release.

Poly(D,l-lactide-co-glycolide) particles are metabolised by the gut microbiome and elevate short chain fatty acids

The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs.

Evaluation of Hydroxyethyl Cellulose Grades as the Main Matrix Former to Produce 3D-Printed Controlled-Release Dosage Forms.

Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability.

Polymer Coated Polymeric (PCP) Microneedles for Controlled Delivery of Drugs (Dermal and Intravitreal)

Microneedles are used to deliver drugs topically across the skin and mucous membranes. Dissolvable microneedles are made using soluble polymers, which disintegrates in the tissue and release the entire payload instantaneously including the polymer construct. Often, a slow release of drug into the tissue is desirable to overcome the severity of side effects at the site of administration as well as systemic adverse effects. In addition, controlled release of active pharmaceutical ingredient (API) only (not the excipients) is safe and effective particularly when the drug delivery is intended to sensitive organs like the eye. In this project, the feasibility of fabricating polymer coated polymeric (PCP) microneedles to achieve a gradual release of only the active ingredient from the device was investigated. The potential application of such PCP microneedles in the dermal and intravitreal drug delivery was also explored using animal tissue models. The PCP microneedles were found to be intact even after prolonged contact with the release medium. The time at which 50% (T50%) of dextran (10 K) was released in case of microneedles prepared using 20% of core polymer (PVP-K30) was about 15 min versus less than 5 min in the case of uncoated microneedles. Whereas when the core polymer concentration was increased to 50%, the T50% was increased to 90 min. The rate of release depended on the polymer molecular weight grade. The rate of drug release was not influenced by the total amount of concentration of dextran. The PCP microneedles of lidocaine hydrochloride could constantly release the drug for up to 9 h in the skin tissue. Likewise, the PCP microneedles infused voriconazole, intravitreally for 6 h.

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy.

Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC-L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R2 = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care.

Orally disintegrating films: The effects of water content on disintegration and mechanical properties

Orally disintegrating films (ODFs) are one of the most important pharmaceutical oral dosage forms. However, it has been noted that the hygroscopicity of ODFs damages their stability and mechanical strength. We prepared model ODFs with three different water contents by storage under different relative humidity conditions in order to examine the effect of the water content on the films’ mechanical properties and the disintegration time. We used three molecular-weight (MW) grades of hydroxypropyl celluloses (HPCs), polyvinyl alcohol (PVA) and pullulan (PUL) as film-formers, and glycerin (GLY) as a plasticizer. With increases of the water content, the ODFs showed significantly decreased tensile strength but no marked change in disintegration time. Water content had the greatest effect on the PVA films containing GLY (10–20%). In addition, PUL films showed the highest water adsorption under all humidity conditions but maintained their excellent mechanical properties. We also elucidated the hygroscopicity of the ODFs formulated with the different polymers and plasticizer by means of a dynamic vapor sorption (DVS) analysis. Our findings provide useful information about the effects of different water contents and storage conditions on ODFs.

Oxidized xylan additive for nanocellulose films – A swelling modifier

Polymeric wood hemicelluloses are depicted to join cellulose, starch and chitosan as key polysaccharides for sustainable materials engineering. However, the approaches to incorporate hemicelluloses in emerging bio-based products are challenged by lack of specific benefit, other than the biomass-origin, although their utilization would contribute to sustainable material use since they currently are a side stream that is not valorized. Here we demonstrate wood-xylans as swelling modifiers for neutral and charged nanocellulose films that have already entered the sustainable packaging applications, however, suffer from humidity sensitivity. The oxidative modification is used to modulate the water-solubility of xylan and hence enable adsorption in an aqueous environment. A high molecular weight grade, hence less water-soluble, adsorbed preferentially on the neutral surface while the adsorbed amount on a negatively charged surface was independent of the molecular weight, and hence, solubility. The adsorption of the oxidized xylans on a neutral cellulose surface resulted in an increase in the amount of water in the film while on the negatively charged cellulose the total amount of water decreased. The finding of synergy of two hygroscopic materials to decrease swelling in hydrophilic bio-polymer films demonstrates the oxidized macromolecule xylan as structurally functional component in emerging cellulose products.

Abstract PS12-04: Rintodestrant (G1T48), an oral selective estrogen receptor degrader in ER+/HER2- locally advanced or metastatic breast cancer: Updated phase 1 results and dose selection

Abstract Background: Rintodestrant (G1T48) is a potent oral selective estrogen receptor degrader (SERD) that competitively binds to the estrogen receptor (ER) and blocks ER signaling in tumors resistant to other endocrine therapies. Preliminary results from Part 1 dose escalation showed robust target engagement on 18F-fluoroestradiol positron emission tomography (FES-PET), a favorable safety profile, and encouraging antitumor activity in patients with heavily pretreated ER+/HER2- advanced breast cancer (ABC), including those with ESR1 mutations (Dees et al., ESMO 2019 [abstract #3587]). Here, we present updated results from dose escalation and expansion (Parts 1 and 2). Methods: This Phase 1, first-in-human, open-label study evaluated rintodestrant monotherapy in women with ER+/HER2- ABC after progression on endocrine therapy. Part 1 was a 3+3 dose escalation (200-1000 mg once daily [QD]); Part 2 expanded 600 and 1000 mg QD; and Part 3 was added to assess rintodestrant with palbociclib in patients in earlier lines in the advanced setting. Primary objectives included dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), safety, and recommended Phase 2 dose. Secondary objectives included pharmacokinetics and antitumor activity (RECIST v1.1). Exploratory objectives included pharmacodynamic inhibition of ER target engagement (FES-PET), mutation profiling (cell-free DNA [cfDNA]), and change in ER expression from baseline to on-treatment tumor biopsies. Results: As of May 13, 2020, 67 patients (Part 1: n = 26; Part 2: n = 41) were treated, with a median age of 61 years (range 34-83) and ECOG PS of 0 (49%) or 1 (51%). Median number of prior lines in the advanced setting was 2 (range 0-9), including prior fulvestrant (64%), CDK4/6 inhibitor (69%), mTOR inhibitor (22%), and/or chemotherapy (46%). Median number of prior lines of endocrine therapy in the advanced setting was 2 (range 0-5), with 61% of patients having received ≥2 lines. Treatment-related adverse events (TRAEs) were reported in 70% of patients. The most common TRAEs in ≥10% of patients included hot flush (24%), fatigue (21%), nausea (19%), diarrhea (18%), and vomiting (10%), mostly grade 1 or 2. No DLTs were reported and MTD was not reached. Dose reduction due to TRAEs occurred in 1 patient (1%), with elevated transaminases (grade 3 ALT and grade 2 AST) at 600 mg. Serious TRAEs occurred in 2 patients at 1000 mg (grade 5 cerebral hemorrhage in the setting of low molecular weight heparin and grade 2 upper abdominal pain). Two patients (3%) discontinued treatment due to TRAEs. Overall, the frequency of patients with TRAEs at 800 mg was comparable with that at 600 mg (57% vs 63%) and less than that at 1000 mg (81%). Of 67 patients, 16 were on study treatment for ≥24 weeks and 3 (n = 1 at 600 mg; n = 2 at 1000 mg, including 1 with ESR1 mutation) had a confirmed partial response (clinical benefit rate [CBR]: 28%). FES-PET standard uptake values decreased at week 4 with a mean reduction of 87% (±8%) at doses ≥ 600 mg. Of 59 patients tested for baseline cfDNA, 41% harbored ≥1 ESR1 mutation, with a similar CBR in both groups (33% in ESR1 mutant and 29% in ESR1 wild-type). Seven of 9 patients had a decrease in ER immunohistochemistry H-score at both 600 and 1000 mg (median [range]: -27.8% [-33.8%, -3.4%]), irrespective of ESR1 mutation status. Based on safety, efficacy, and ER degradation, 800 mg was selected as the optimal dose for further study. Conclusions: Rintodestrant continues to demonstrate an excellent safety/tolerability profile across all doses, with promising antitumor activity in patients with heavily pretreated ER+/HER2- ABC, including those with tumors harboring ESR1 mutations. Part 3 of this study, evaluating rintodestrant 800 mg QD with palbociclib in a more endocrine-sensitive population, is ongoing (NCT03455270). Citation Format: Philippe Aftimos, Patrick Neven, Mark Pegram, Catharina Willemien Menke-van der Houven van Oordt, E. Claire Dees, Carolien Schröder, Agnes Jager, Iurie Bulat, Linnea Chap, Marina Maglakelidze, Erika Hamilton, Massimo Cristofanilli, Susanna Ulahannan, Jorianne Boers, Ramsha Iqbal, Adrian Crijanovschi, Curt D Wolfgang, Wenli Tao, Christina Sipes, Rajesh Malik, Sarika Jain. Rintodestrant (G1T48), an oral selective estrogen receptor degrader in ER+/HER2- locally advanced or metastatic breast cancer: Updated phase 1 results and dose selection [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-04.

Synthesis and evaluation of novel corrosion inhibitors utilized from the recycling of polyethylene terephthalate polymer: Gravimetric, electrochemical, quantum chemical modeling, and molecular docking studies

Herein, glycolysis reaction was performed for managing of disposed polyethylene terephthalate (PET) using various molecular weight grades of polyethylene glycol. The glycolyzed-PET intermediates were converted into their active bromide derivatives throughout the interaction by bromoacetic acid. The active bromide derivatives were reacted by pyridine to yield the cationic bromide compounds. Assemblies of the finally produced compounds were chemically recognized by spectroscopic determination (FTIR, 1H NMR). The glycolyzed PET compounds functionalized by cationic quaternary groups were assessed for their anticorrosive properties and the protection of pipelines in oilfields against deterioration. The composites were assessed at different concentrations in a simulant medium of the oil wells (0.5 M H2SO4). Furthermore, the bacterial potencies of the organized composites were assessed in contradiction of diverse bacteria's strains using minimum inhibition concentration (MIC) evaluation. The results of mass decline and electro-chemical evaluations on carbon steel revealed that the products are exhibited excellent anticorrosive and antimicrobial efficiencies.

Rainfastness of agrochemical formulations based on N-vinyl pyrrolidone polymers and their interpolymer complexes with poly(acrylic acid)

In this study, poly(N-vinyl pyrrolidone) (PVP), a cheap, safe and non-toxic polymer, was explored using a range of analytical methods including fluorescence microscopy to gain insight into the role of polymer physicochemical properties on rainfastness, i.e. tenacity of foliar deposits against rain, of agrochemicals on plant surfaces. Three methods were approached to increase rainfastness of PVP, i.e. using high molecular weight grades of the polymer, pre- blending PVP with poly(acrylic acid) (PAA) and successively depositing drops of each polymer (PVP or PAA) on top of the other. Regarding the first method, from the different commercial grades of PVP studied, it was revealed that the polymer with highest molecular weight (1300 kDa) significantly improved the rainfastness of a model fungicide (azoxystrobin). The rainfastness results correlated with film dissolution in water. In the second method, rainfastness properties of PVP were improved by mixing it with PAA and it was shown that PVP-PAA mixtures at the 50:50 wt ratio retarded film dissolution by a factor of 2–3 compared to the PVP alone. In the third method, a novel approach was employed by placing drops of PAA solution on PVP drops on paraffin film and leaving to physically mix and dry down. In this proof-of-concept study, the washing-off profiles of the dry deposits revealed a striking rainfastness increase almost to the level of the insoluble controls. Methods employed in this study to increase rainfastness of agrochemical formulations can explain the previously reported effects of water-soluble polymers on rainfastness and allows the identification of improved rainfastness aids.

High-Performance Polyesters: Synthesis, Characterization, and Properties of Poly(P-Oxybenzoate)

Poly (p-oxybenzoate) samples were synthesized via the esterification and the transesterification reactions. The structure of the obtained target products was investigated by IR spectroscopy and has revealed that these substances were oligomers. The transesterification method has facilitated the synthesis of higher molecular weight grades of the polymer. This resulted in enhanced thermal properties of polyester synthesized by transesterification (up to 340 °C). The other specimen has performed thermal stability up to 320 °C.

Study of properties of polyethylene and cement mixtures

Polyethylene is used in a myriad of ways, from low molecular weight polyethylene (PE) being used as a lubricant and mold release, to higher molecular weight grades being used for fiber, films, molding resins, etc. According to the advantages of PE as stiffness, light weight plastic and having excellent chemical resistance, polyethylene and cement mixtures can offer considerable benefits to product performance, marketing aspects and differentiation of cement products. The objective of this investigation is to study the influence of PE on the properties of cements. In this paper a portion of ordinary Portland cement OPC was replaced by polyethylene powder, with four different rates (5%, 10%, 15% and 20%). Paste of each cement was prepared and analyzed for its setting time, expansion and strength. In this experimental study with 10% of PE the maximum strength is achieved for 28 days. Moreover, in order to benefit from thermoplastic and viscoelastic properties of PE, we exposed specimens of polymer mortar to a thermal cycle in a temperature ranging from 25 up to 130 °C. The results show some development of strength.

Potential of low molecular weight natural polysaccharides for colon targeted formulation and its evaluation in human by Gamma Scintigraphy

Colonic drug targeting is an elusive goal, implicated for localized drug and systemic delivery of proteins which otherwise cannot be delivered by oral route. The purpose of the present work was to evaluate the suitability of formulation design of compression coating and potential of low molecular weight natural polysaccharides for colonic drug targeting using Gamma Scintigraphy in human subjects and to establish platform technology. Before commencing with in vivo imaging studies in human by Gamma Scintigraphy, we performed in vitro release studies and scanning electron microscopy for surface topography of tablet formulations subjected to in vitro dissolution study. We investigated the applicability of low molecular weight and low viscosity grade Guar gum ULV 1000 and Pectin with low degree of methoxylation 9% as for site specific delivery. Gamma Scintigraphy imaging of formulation with biopolymer in human subject showed the transit of tablet intact in colon with average arrival time being 5.75 h and the activity was released continuously for 30 h. Scanning electron microscopy for surface topography of tablets subjected to simulated colonic fluid showed erosion caused by microbial flora of the colon. Taken together, compression coating design with low molecular weight biopolymer can serve as a platform technology to deliver other potential molecules to the colonic region for local and/or systemic effects in other therapeutic areas.

Fabrication and performance evaluation of blood compatible hemodialysis membrane using carboxylic multiwall carbon nanotubes and low molecular weight polyvinylpyrrolidone based nanocomposites.

This study focused to optimize the performance of polyethersulfone (PES) hemodialysis (HD) membrane using carboxylic functionalized multiwall carbon nanotubes (c-MWCNT) and lower molecular weight grade of polyvinylpyrrolidone (PVP-k30). Initially, MWCNT were chemically functionalized by acid treatment and nanocomposites (NCs) of PVP-k30 and c-MWCNT were formed and subsequently blended with PES polymer. The spectra of FTIR of the HD membranes revealed that NCs has strong hydrogen bonding and their addition to PES polymer improved the capillary system of membranes as confirmed by Field Emission Scanning Electron Microscope (FESEM) and leaching of the additive decreased to 2% and hydrophilicity improved to 22%. The pore size and porosity of NCs were also enhanced and rejection rate was achieved in the establish dialysis range (<60 kDa). The antifouling studies had shown that NCs membrane exhibited 30% less adhesion of protein with 80% flux recovery ratio. The blood compatibility assessment disclosed that NCs based membranes showed prolonged thrombin and prothrombin clotting times, lessened production of fibrinogen cluster, and greatly suppressed adhesion of blood plasma than a pristine PES membrane. The results also unveiled that PVP-k30/NCs improved the surface properties of the membrane and the urea and creatinine removal increased to 72% and 75% than pure PES membranes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 513-525, 2019.

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12 h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.

Towards a sulfur clean fuel: Deep extraction of thiophene and dibenzothiophene using polyethylene glycol-based deep eutectic solvents

In this work, extractive desulfurization of model fuel containing dibenzothiophene (DBT) and thiophene (Th) as sulfur compounds was carried out using 16 different Deep Eutectic Solvents (DES) based on polyethylene glycol (PEG) and its precursors. The aim of this study is the reduction of the sulfur content of fuels below the environmental regulation (10 ppm), using PEG-based DES as low-cost extraction media under mild conditions and to compare their extractive performance with that of PEG alone, which by itself is a green solvent. For that purpose, 7 different quaternary ammonium and phosphonium salts were combined with four different molecular weight grades of PEG and PEG precursors such as ethylene glycol and triethylene glycol. The best results were obtained for the DES composed of tetrabutylammonium chloride (TBAC) and PEG400, which showed that it is possible to achieve, in single extraction step, 85% and 68% of extraction efficiency, and deep desulfurization in 2 and 3 cycles, for DBT and Th, respectively. In addition, this DES is not soluble in the model fuel and its extraction capacity is independent on the starting sulfur concentration. Finally, after being reused six times, TBAC:PEG400 DES still maintained 53% and 17% of its capacity, for DBT and Th removal, respectively, and after a regeneration step the performance of the DES was fully recovered.

Optimization study of polyethylene glycol and solvent system for gas permeation membranes

Cellulose acetate (CA) membranes blended with Polyethylene glycol (PEG) in acetone–water solvent system were synthesized by using solution-casting method that resulted in the formation of flexible, white membranes. Different molecular weight (MW) grades of PEG (including MW 1000, 10,000 and 20,000 g/mol) were used. Cast membranes were tested for tensile strength and permeability at different loading of PEG MW 10,000 and 20,000 g/mol. Excellent flexible membranes were produced in acetone–water solvent system in the presence of PEG, which were otherwise brittle. Surface structure and morphology were analysed using scanning electron microscopy. The presence of different functional groups was confirmed using Fourier transform infra-red spectroscopy and the mechanical characteristics were studied by tensile testing. The introduction of PEG caused an increase in permeability of the membranes. The increase in permeability is due to the opening up of pores as the membrane becomes more flexible, when the plasticizer is added. The permeability continues to increase with the addition of PEG. Moreover, the resulting membranes are not only more flexible, but also have largely improved tensile strength as compared to the CA membranes without PEG. This improved tensile strength can also be attributed to the improved flexibility of the membrane. A trade-off is reached between tensile strength and permeability as increasing amount of PEG improves tensile strength but the resulting membrane becomes too permeable to be used for gas separation. Moreover, using PEG of higher MW resulted in porous membranes, even at low amounts of PEG. Therefore, we concluded that CA membrane with less amount of low-MW PEG (i.e. 5% PEG of MW 1000 g/mol) must be used to optimize both permeability and tensile strength of the membrane.

Development and Characterisation of Natamycin Mini-Matrices Prepared by Hot-Melt Extrusion for Vaginal Delivery

In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies and in vitro mucoadhesion test were performed. High molecular weight grades of KlucelTM hydroxypropylcellulose were used as a thermoplastic polymer. TEC and PEG 400 were chosen as plasticizer. According to the obtained results of melt viscosity measurements, the maximum torque of extrudates prepared using PEG 400 increased with increasing drug loading. The thermo-gravimetric analyses showed that natamycin is stable up to 198℃ and this result gives the opportunity to hot melt extrussion process at 90℃. In vitro drug release results showed that the release was extended up to 72 hours and drug release rate increased with increasing drug loading. In respect to the in vitro mucoadhesion test results, the values of work of mucoadhesion were found high as 771,977 mN.mm, 753,199 mN.mm, 686,356 mN.mm for the prepared hot melt extruded mini-matrices. Our results showed that the developed formulations were found worthy of further studies.