Supramolecular Interaction of Atenolol and Propranolol with ß-Cyclodextrin Spectroscopic Characterization and Analytical Application.

Atenolol (ATE) and propranolol (PRO) inclusion complexes with ß-cyclodextrin have been investigated in aqueous solution. The aqueous solution was examined and characterized using UV-vis, fluorescence spectroscopy, and 1H NMR. The physical mixture was characterized using FTIR. The existence of inclusion complexes is confirmed by observing changes in spectroscopic properties. The ATE complex with ß-CD exhibited an interaction as host and (ß-CD) as a guest in a 1:1 ratio, with an inclusion constant K of 2.09 × 10-3 µM-1, as determined by the typical double-reciprocal graphs. Similarly, the PRO complex with ß-CD exhibited an interaction as host and (ß-CD) guest in 1:1 and 1:2 stoichiometry at the same time; the inclusion constants were K1 = 5.80 × 10-5 µM-1 and K2 = 4.67 × 10-8 µM-1, as determined by typical double-reciprocal graphs. The variables influencing the formation of the inclusion complexes were investigated and optimized. Based on the enhancement in fluorescence intensity due to the formation of inclusion complexes, spectrofluorometric methods were developed and validated for determination of each drug's pharmaceutical formulation. The quantification of the fluorescence intensity for ATE and PRO was conducted at λex/λem 226/302 nm and λex/λem 231/338 nm, respectively. Under the optimal reaction circumstances, linear relationships with good correlation coefficients of 0.9918 and 0.99 were found in the concentration ranges of 0.3-1.7 µM, and 0.1-1.1 µM for ATE and PRO, respectively. The limits of detection (LODs) were found to be 0.13 and 0.01 µM for ATE and PRO, respectively. The suggested approach was effectively applied to the analysis of both drugs' pharmaceutical formulations.

Label-Free Screening of Drug-Induced Liver Injury Using Stimulated Raman Scattering Microscopy and Spectral Phasor Analysis.

Hepatic toxicity is a leading cause of the termination of clinical trials and the withdrawal of therapeutics following regulatory approval. The detection of drug-induced liver injury (DILI) is therefore of importance to ensure patient safety and the effectiveness of novel small molecules and drugs. DILI encompasses drug-induced steatosis (DIS) and drug-induced phospholipidosis (DIPL) which involve the accumulation of excess intracellular lipids. Here, we develop hyperspectral stimulated Raman scattering (SRS) microscopy as a label-free methodology for discriminating DIS and DIPL in mammalian cell culture. We demonstrate that hyperspectral SRS imaging in tandem with spectral phasor analysis is capable of discriminating DIS and DIPL based on the nature and distribution of intracellular lipids resulting from each process. To demonstrate the practical application of this methodology, we develop a panel of alkyne-tagged propranolol analogues that display varying DILI effects. Using hyperspectral SRS imaging together with spectral phasor analysis, our label-free methodology corroborated the standard fluorescence-based assay for DILI. As a label-free screening method, it offers a convenient and expedient methodology for visualizing hepatotoxicity in cell cultures which could be integrated into the early stages of the drug development process for screening new chemical entities for DILI.

A high-affinity, cis-on photoswitchable beta blocker to optically control ß2-adrenergic receptors in vitro and in vivo.

This study introduces (S)-Opto-prop-2, a second-generation photoswitchable ligand designed for precise modulation of ß2-adrenoceptor (ß2AR). Synthesised by incorporating an azobenzene moiety with propranolol, (S)-Opto-prop-2 exhibited a high PSScis (photostationary state for cis isomer) percentage (∼90 %) and a favourable half-life (>10 days), facilitating diverse bioassay measurements. In vitro, the cis-isomer displayed substantially higher ß2AR binding affinity than the trans-isomer (1000-fold), making (S)-Opto-prop-2 one of the best photoswitchable GPCR (G protein-coupled receptor) ligands reported so far. Molecular docking of (S)-Opto-prop-2 in the X-ray structure of propranolol-bound ß2AR followed by site-directed mutagenesis studies, identified D1133.32, N3127.39 and F2896.51 as crucial residues that contribute to ligand-receptor interactions at the molecular level. In vivo efficacy was assessed using a rabbit ocular hypertension model, revealing that the cis isomer mimicked propranolol's effects in reducing intraocular pressure, while the trans isomer was inactive. Dynamic optical modulation of ß2AR by (S)-Opto-prop-2 was demonstrated in two different cAMP bioassays and using live-cell confocal imaging, indicating reversible and dynamic control of ß2AR activity using the new photopharmacology tool. In conclusion, (S)-Opto-prop-2 emerges as a promising photoswitchable ligand for precise and reversible ß2AR modulation with light. The new tool shows superior cis-on binding affinity, one of the largest reported differences in affinity (1000-fold) between its two configurations, in vivo efficacy, and dynamic modulation. This study contributes valuable insights into the evolving field of photopharmacology, offering a potential avenue for targeted therapy in ß2AR-associated pathologies.

Analytical QbD for the optimization of a multimode HPLC method for the investigation of hydrochlorothiazide, diltiazem and propranolol release from 3D printed formulation.

Since 3D printing technology is an emerging field in pharmaceutical technology, the present study aimed at the development of a mixed-mode liquid chromatographic method for the separation and determination of hydrochlorothiazide, diltiazem, and propranolol to investigate their in-vitro release performance from 3D printed tablets. Due to the unique properties of the mixed-mode stationary phase, the three drugs were separated in less than 8 min under isocratic elution. Method development was accomplished following the Analytical Quality by Design principles and was evaluated using risk assessment and multivariate analysis. The influences of critical method parameters on critical method attributes (were screened using a 2-level fractional factorial design and subsequently optimized through a central composite design. The method operable design region was approved by the establishment of a robust zone using Monte Carlo simulation and capability analysis. The validation of the HPLC method was performed based on the total error concept. The relative bias was varied between ─ 11.6 % and 10.5 % and the RSD values for repeatability and intermediate precision were below 4.4 % in all cases. The limits of detection (LOD) ranged between 0.17 - 0.90 µg/mL and were adequate for the specific application. The developed method was successfully applied to the analysis of the studied drugs in in-vitro drug release samples obtained from 3D-printed tablets combining the above-mentioned active pharmaceutical ingredients (APIs).

Chitosan decorated oleosomes loaded propranolol hydrochloride hydrogel repurposed for Candida albicans-vaginal infection.

Aim: Our investigation aims to estimate the antifungal effect of propranolol hydrochloride (PNL). Methods: Oleosomes (OLs) were fabricated by thin-film hydration and evaluated for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and amount of drug released after 6 h Q6h (%). Results: The optimal OL showed a rounded shape with optimum characteristics. The ex-vivo permeation and confocal laser scanning microscopy verified the prolonged release and well deposition of PNL-loaded OLs-gel. The in-silico assessment demonstrated the good stability of PNL with OLs' ingredients. In vivo evaluations for PNL-loaded OLs-gel showed a good antifungal impact against Candida albicans with good safety. Conclusion: This work highlights the potential of PNL-loaded OLs-gel as a potential treatment for candida vaginal infection.

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Elucidating the enhanced role of carbonate radical in propranolol degradation by UV/peroxymonosulfate system.

Carbonate radical (CO3•-) has been proved to be an important secondary radical in advanced oxidation processes due to various radical reactions involved HCO3-/CO32-. However, the roles and contributions of CO3•- in organic micropollutant degradation have not been explored systematically. Here, we quantified the impact of CO3•- on the degradation kinetics of propranolol, a representative pollutant in the UV/peroxymonosulfate (PMS) system, by constructing a steady-state radical model. Substantially, the measured values were coincident with the predictive values, and the contributions of CO3•- on propranolol degradation were the water matrix-dependent. Propranolol degradation increased by 130% in UV/PMS system containing 10 mM HCO3-, and the contribution of CO3•- was as high as 58%. Relatively high pH values are beneficial for propranolol degradation in pure water containing HCO3-, and the contributions of CO3•- also enhanced, while an inverse phenomenon was shown for the effects of propranolol concentrations. Dissolved organic matter exhibited significant scavenging effects on HO•, SO4•-, and CO3•-, substantially retarding the elimination process. The developed model successfully predicted oxidation degradation kinetics of propranolol in actual sewage, and CO3•- contribution was up to 93%, which in indicative of the important role of CO3•- in organic micropollutant removal via AOPs treatment.

3D printing of customized bioceramics for promoting bone tissue regeneration by regulating sympathetic nerve behavior.

Numerous studies have shown that there are multiple neural activities involved in the process of bone resorption and bone regeneration, and promoting osteogenesis by promoting neural network reconstruction is an effective strategy for repairing critical size bone defects. However, traumatic bone defects often cause activation of the sympathetic nervous system (SNS) in the damaged area, releasing excess catecholamines (CAs), resulting in a decrease in the rate of bone formation. Herein, a 3D-printed scaffold loaded with propranolol (PRN) is proposed to reduce CA concentrations in bone defect areas and promote bone regeneration through drug release. For this purpose, PRN-loaded methacrylated gelatin (GelMA) microspheres were mixed with low-concentration GelMA and perfused into a 3D-printed porous hydroxyapatite (HAp) scaffold. By releasing PRN, which can block ß-adrenergic receptors, it hinders the activation of sympathetic nerves and inhibits the release of excess CA by the SNS. At the same time, the composite scaffold recruits bone marrow mesenchymal stem cells (BMSCs) and promotes the differentiation of BMSCs in the direction of osteoblasts, which effectively promotes bone regeneration in the rabbit femoral condyle defect model. The results of the study showed that the release of PRN from the composite scaffold could effectively hinder the activation of sympathetic nerves and promote bone regeneration, providing a new strategy for the treatment of bone defects.

Plant leaf mucilage/carrageenan/Eudragit® NE30D blended films: Optimization, characterization, and pharmaceutical application.

Mucilage of C. pareira leaves was utilized, being manufactured for use in pharmaceutical products. Carrageenan and Eudragit® NE30D were used to combined. Glycerin was used as a plasticizer at a concentration of 20 % w/w based on the amount of polymer used. Computer software optimized its characteristics, including tensile properties, moisture uptake, and erosion; the optimal formulation was 1.4:1.2:2.8. The percentages of optimization error ranged from 8.48 to 13.80 %. Propranolol HCl was mixed to an optimal formulation. The film layer was tight, homogeneous, and smooth, with no holes. DSC thermogram showed no interaction peaks at 101.33 °C and 170.50 °C. Propranolol HCl concentration in the film ranged from 2.18 to 2.20 mg/cm2. Propranolol HCl was quickly released from the film. The kinetic model for the release profile was first-order kinetic. Although propranolol HCl had a high-release profile, its skin permeation was limited. The permeation lag time, Jss, and Kp were 1.60-2.65 h, 0.0182-0.0338 µg/cm2/h, and 9.10-15.35 cm/h, respectively. A significant amount of propranolol HCl residue was found on the skin's surface. Glycerin appeared to influence propranolol HCl permeability. Therefore, the plant leaf mucilage/carrageenan/Eudragit® NE30D blended film can be utilized in pharmaceutical applications to control drug release from its film layer.

Impact of dispersion time interval and particle size on release profiles of propranolol HCl and carbamazepines from microparticle blends system.

The objective of this study was to investigate the effect of dispersion time interval (DTI) on physicochemical properties of drug following the incorporation of propranolol HCl (Pro) and carbamazepine (CBZ) within ethyl cellulose (EC) microparticle blends using solvent evaporation method. The first Pro emulsion and second CBZ oil phase were dispersed in an external aqueous phase, with DTI of 0 and 60 min. The morphology of microparticle blends were characterized by SEM. The particle size mean of the emulsion droplets/hardened microparticles were monitored by FBRM. Encapsulation efficiency (EE) and in vitro drug release were also investigated. The resulting microparticle blends were spherical and formed two populations. The particle size mean of microparticle blends ranged from 113.27 µm to 122.42 µm. The EE was 77.28% to 78.64% for Pro and 96.48% to 98.64% for CBZ. FBRM studies showed that the size of microparticle blend prepared as W/O/W (Pro) and O/W (CBZ) system with DTI of 60 min and stirring time 4 h were larger than those prepared with DTI of 0 min. In vitro drug release studies after 28 days that revealed the CBZ release (58.72%) was faster than Pro release (43.16%). Investigation on surface morphology by SEM showed that the second drug CBZ which added as the oil phase in the W/O/W emulsion system had blocked the pores on the surface Pro microparticles prepared from the first primary emulsion, therefore affecting the drug release. This blocking effects of second drug (CBZ) on first emulsion microparticles (Pro) depended on the DTI. This phenomenon is only applicable if the first primary emulsion is W/O/W system.

Development and Evaluation of a Physiologically Based Pharmacokinetic Drug-Disease Model of Propranolol for Suggesting Model Informed Dosing in Liver Cirrhosis Patients.

AIM: The study was aimed to understand the underlying causes for the differences in propranolol pharmacokinetics (PK) between healthy and cirrhosis populations by using a systematic whole-body physiologically based pharmacokinetic (PBPK) model-building approach for suggesting model informed propranolol dosing in liver cirrhosis patients with different stages of disease severity. METHODS: A whole-body PBPK model was developed by using population simulator PK-Sim® by using reported physicochemical and clinical data for propranolol in healthy and liver cirrhosis populations. The model evaluation was done by visual verification and comparison of PK parameters using their observed/predicted ratios (Robs/pred). RESULTS: The developed model has effectively described the disposition of propranolol after intravenous and oral application in healthy and liver cirrhosis populations. All the model predictions were comparable to the observed clinical data and the Robs/pred for all the PK parameters were within a 2-fold range. A significant increase in plasma concentration of propranolol and decrease in drug clearance was observed in progressive stages of liver cirrhosis. The developed model after evaluation with the reported clinical PK data was used for suggesting model informed propranolol dosing in different stages of liver cirrhosis based on systemic unbound drug concentration. CONCLUSION: The developed PBPK model has successfully described propranolol PK in healthy and cirrhosis populations after IV and oral administration. The evaluated PBPK propranolol-cirrhosis model can have many implications in predicting propranolol dosing in liver cirrhosis patients with different stages of disease severity.

Toward an automated workflow for the study of plasma protein-drug interactions based on capillary electrophoresis-frontal analysis combined with in-capillary mixing of interacting partners.

Capillary electrophoresis-frontal analysis (CE-FA) together with mobility shift affinity CE is the most frequently used mode of affinity CE for a study of plasma protein-drug interactions, which is a substantial part of the early stage of drug discovery. Whereas in the classic CE-FA setup the sample is prepared by off-line mixing of the interaction partners in the sample vial outside the CE instrument and after a short incubation period loaded into the capillary and analysed, in this work a new methodological approach has been developed that combines CE-FA with the mixing of interacting partners directly inside the capillary. This combination gives rise to a fully automated and versatile methodology for the characterization of these binding interactions besides a substantial reduction in the amounts of sample compounds used. The minimization of possible experimental errors due to the full involving of sophisticated CE instrument in the injection procedure, mixing and separation instead of manual manipulation is another fundamental benefit. The in-capillary mixing is based on the transverse diffusion of laminar flow profile methodology introduced by Krylov et al. using its multi-zone injection modification presented by Remínek at al.. Actually, after the method optimization, the alternate introduction of six plugs of drug and six plugs of bovine serum protein in BGE, each injected for 3 s at a pressure of -10 mbar (-1 kPa) into the capillary filled by BGE, was found to be the best injection procedure. The method repeatability calculated as RSDs of plateau highs of bovine serum albumin and propranolol as model sample compounds were better than 3.44 %. Its applicability was finally demonstrated on the determination of apparent binding parameters of bovine serum albumin for basic drugs propranolol and lidocaine and acid drug phenylbutazone. The values obtained by a new on-line CE-FA methodology are in agreement with values estimated by classic off-line CE-FA, as well as with literature data obtained using different techniques.

An Herbal Nanohybrid Formula of Epigallocatechin Gallate-Chitosan-Alginate Efficiently Restrict the Sexual Dysfunction Adverse Effect of ß-Adrenergic Antagonist Drug: Propranolol.

The clinical studies proved the adverse effect of Propranolol on sexual function. Regarding this issue, the key research question of this study was, whether the designed herbal nanohybrid formula EGCG-chitosan-alginate has an efficacy versus Propranolol, or not? The formula was optimized according to the coacervation method. Its molecular structure and characteristics were confirmed. The entrapment efficiency was determined, and the stability, as well in vitro release study was conducted. The in vivo study was conducted for 65 days. To answer the raised question, tissue weights of the testis, epididymis seminal vesicles, and prostate were determined. Oxidative stress markers as MDA and GSH were measured in testis and epididymis, while testosterone in blood serum. The semen analysis was performed. DNA damage was detected according to the comet assay procedures. Conventional pathological examination was done in special concern to testis and epididymis. The characterization results reflected the good preparation of the formula with an amorphous structure in a range of 200 nm, high stability with ZP + 57.3 mV. The calculated EE was 84.10 ± 1.19% and the release percent was 72.11 ± 0.77% for 24 hrs. All the rats increased in the weight with variations among the groups in the tissue organs. The finding exposed a significant decrease in the average of MDA in the rats' testes with a significant increase in GSH while a non-significant difference in the epididymis, in both. The testosterone, the seminal parameters, and the DNA integrity significantly increased in the nano-formula compared to propranolol. Likewise, normal pathological findings of the nano-formula in the testis and Epididymis compared to abnormal of propranolol. In total, the current research confirmed that EGCG had no toxic effects and able to promote fertility. The most important finding was the administration of EGCG either in normal or nano-form prior to propranolol alleviated the effects of propranolol. These findings reflected the protection evident of EGCG versus propranolol.

ß-Cyclodextrin Polymerized in Cross-Flowing Channels of Biomass Sawdust for Rapid and Highly Efficient Pharmaceutical Pollutants Removal from Water.

Water pollution arising from pharmaceuticals has raised great concerns about the potential risks for biosphere and human health. However, rapid and efficient removal of pharmaceutical contaminants from water remains challenging. Wood sawdust, a byproduct of the wood-processing industry, is an abundant, cost-effective, and sustainable material with a unique hierarchically porous microstructure. These features make wood sawdust quite interesting as a filtration material. Here, we report a novel cross-flow filtration composite based on ß-cyclodextrin-polymer-functionalized wood sawdust (ß-CD/WS) in which the pharmaceutical contaminant water flows through the sawn-off vessel channels and the micropores on the surface of the cell walls, generating the turbulence. Such water flow characteristics ensure full contact between pharmaceutical pollutants and ß-CD grafted on the cellulose backbone of wood sawdust, thereby enhancing the water treatment efficiency. Consequently, the ß-CD/WS filter device shows a high removal efficiency of over 97.5% within 90 s for various pharmaceutical contaminants including propranolol, amitriptyline, chlortetracycline, diclofenac, and levofloxacin, and a high saturation uptake capacity of 170, 156, 257, 159, and 185 mg g-1, respectively. The high-performance wood-sawdust-based cross-flow filtration opens new avenues for solving the global water pollution issues, especially those caused by pharmaceutical contaminants.

Clinical Pharmacokinetics of Propranolol Hydrochloride: A Review.

BACKGROUND: Nobel laureate Sir James Black's molecule, propranolol, still has broad potential in cardiovascular diseases, infantile haemangiomas and anxiety. A comprehensive and systematic review of the literature for the summarization of pharmacokinetic parameters would be effective to explore the new safe uses of propranolol in different scenarios, without exposing humans and using virtual-human modeling approaches. OBJECTIVE: This review encompasses physicochemical properties, pharmacokinetics and drug-drug interaction data of propranolol collected from various studies. METHODS: Clinical pharmacokinetic studies on propranolol were screened using Medline and Google Scholar databases. Eighty-three clinical trials, in which pharmacokinetic profiles and plasma time concentration were available after oral or IV administration, were included in the review. RESULTS: The study depicts that propranolol is well absorbed after oral administration. It has dose-dependent bioavailability, and a 2-fold increase in dose results in a 2.5-fold increase in the area under the curve, a 1.3-fold increase in the time to reach maximum plasma concentration and finally, 2.2 and 1.8-fold increase in maximum plasma concentration in both immediate and long-acting formulations, respectively. Propranolol is a substrate of CYP2D6, CYP1A2 and CYP2C19, retaining potential pharmacokinetic interactions with co-administered drugs. Age, gender, race and ethnicity do not alter its pharmacokinetics. However, in renal and hepatic impairment, it needs a dose adjustment. CONCLUSION: Physiochemical and pooled pharmacokinetic parameters of propranolol are beneficial to establish physiologically based pharmacokinetic modeling among the diseased population.

UV-LED/chlorine degradation of propranolol in water: Degradation pathway and product toxicity.

This study reports on the propranolol (PRO) degradation performance and product toxicity of an ultraviolet light-emitting diode (UV-LED)/chlorine process. The effects of experimental parameters including solution pH, chlorine dosage, and water matrix constituents on PRO removal were evaluated. Up to 94.5% of PRO could be eliminated within 15 min at a PRO-to-chlorine molar ratio of 1:4. The overall removal efficiency of PRO was non-pH dependent in the range of 5-9, while the initial rate was accelerated under alkaline conditions. The presence of Cl-/HCO3- had little influence on the PRO degradation, whereas either humic acid or NO3- had an obvious inhibitory effect. Radical scavenger experiments showed that both HO and Cl primarily contributed to the PRO degradation, and electron paramagnetic resonance data demonstrated the generation of 1O2. The transformation of PRO during this process led to five detected products, which exhibited a higher acute toxicity than the parent compound according to the bright luminescent bacillus T3 method. It is worth mentioning that under the same ultraviolet illumination intensity, the degradation of PRO under UV-LED/chlorine gave a better performance than UV254/chlorine, but the EEO of the former is obviously higher than the latter. So further research is required on improving the electric current to photon conversion efficiency for UV-LED. Additionally, the UV-LED/chlorine system was effective in the degradation of other drugs including sulfamethoxazole, oxytetracycline hydrochloride, and gatifloxacin, suggesting the possible application of the UV-LED/chlorine process for the removal of pharmaceuticals during wastewater treatment.

Two dimensional chromatography mass spectrometry: Quantitation of chiral shifts in metabolism of propranolol in bioanalysis.

In this study a heart-cutting 2D-LC method was successfully developed and optimized in order to discriminate and quantitate (S)-propranolol, (R)-propranolol, and its hydroxy metabolites, namely the isomeric (S)-4'­hydroxy propranolol, (R)-4'­hydroxy propranolol, (S)-5'­hydroxy propranolol, (R)-5'­hydroxy propranolol, (S)-7'-hydroxy propranolol, and (R)-7'­hydroxy propranolol in one chromatographic run. Thereby, experiments investigating chiral discrimination in ring hydroxylation of propranolol were made feasible. Analysis of human urine samples after administration of a single oral dose of 40 mg of propranolol clearly revealed considerable chiral shifts in propranolol and its 4'-, 5'-, and 7'-hydroxy metabolites. Furthermore, the excretion rates of the individual (S)- and (R)-enantiomers were continuously monitored over 24 h post administration. Studies were performed utilizing a 2D-LC system hyphenated to a triple quadrupole mass spectrometer. The chromatographic system was endued with a reversed phase column (phenyl-hexyl) in first dimension and a teicoplanin based chiral column in second dimension. The method was basically validated and successfully evaluated as robust. Calibration was performed achieving accuracy between 80% and 120%. Maximal excretion rates of (S)-propranolol, (R)-propranolol, (S)-4'­hydroxy propranolol, (R)-4'­hydroxy propranolol, (S)-5'­hydroxy propranolol, (R)-5'­hydroxy propranolol, and (R)-7'­hydroxy propranolol were 237 ng/min, 281 ng/min, 4 ng/min, 4 ng/min, 1 ng/min, 9 ng/min, and 3 ng/min, respectively.

Quantification of porogen effect on the drug release from single- and multi-layered ethylcellulose coated pellets containing single or combined drugs.

The aim of this work was to develop a mathematical model to estimate the drug release from a conventional single-compartment reservoir pellet and extend its applicability to multi-compartment reservoir pellets. Conventional pellets were prepared by layering the drug onto starter-core then applying various ethylcellulose/HPC coatings for drug release control. Multi-layered pellets comprised a first drug layer of propranolol HCl (D1) followed by a first controlled release coating (C1) and consecutively a second drug layer of carbamazepine or caffeine (D2) and then a second controlled-release coating (C2). Drug release from single- and multi-compartment pellets generally increased with an increase of the water-soluble HPC in the coatings. The response described a sigmoidal curve, which agreed with a cumulative normal distribution function. The developed mathematical model facilitated quantification of the drug release of pellets as a function of the porogen content and the coating level. Additionally, the model was applied successfully in multi-compartment pellets to calculate theses effects on the release of drugs with a broad range of aqueous solubility.

Eudragit RL-based film coatings: How to minimize sticking and adjust drug release using MAS.

Polymeric film coatings based on quaternary polymethacrylates (QPMs, e.g. Eudragits®) are frequently used for controlled release applications. However, their considerable sticking tendency is a major drawback in practice. In this study, different amounts of magnesium aluminum silicate (MAS) were added to the film coatings in order to overcome this hurdle. MAS is negatively charged and can electrostatically interact with the positively charged QPM. Different types of tablet cores were coated with aqueous Eudragit® RL 30D dispersions, optionally containing varying amounts of MAS. Dynamic changes in the wet mass of the systems as well as drug release upon exposure to 0.1 M HCl and phosphate buffer pH 6.8 were monitored. Propranolol HCl, acetaminophen, and diclofenac sodium were used as cationic, nonionic and anionic model drugs. The tablets were optionally cured for 12 h at 45 or 60 °C. Importantly, the addition of MAS to aqueous Eudragit® RL 30D dispersion substantially reduced the films' stickiness and led to stable inner coating structures, even without curing. Desired drug release rates can be adjusted by varying the QPM:MAS ratio and coating level.

SR-FTIR spectro-microscopic interaction study of biochemical changes in HeLa cells induced by Levan-C60, Pullulan-C60, and their cholesterol-derivatives.

Objects of the present study are improved fullerene C60 drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C60 and correspond to the changes in the protein region, i.e. Amide I band, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C60. In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C60-based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C60 potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells.

Light-responsive vesicles for enantioselective release of chiral drugs prepared from a supra-amphiphilic M-helix.

A kind of light-responsive vesicle was prepared by aqueous self-assembly of α-CD and an azobenzene-containing M-helical foldamer, which displayed dynamic disassembly-reassembly structural transformation when alternately irradiated by UV and visible light. Distinctively, this vesicle also exhibited enantioselective release abilities toward racemic propranolol (a ß-blocker), owing to the M-helical building blocks.