Development Of Formulations Research Articles

CARDIOVASCULAR EFFECTS OF FREE OR COMPLEXED LINALOOL WITH Β-CYCLODEXTRIN: A FOCUS FOR ANTIHYPERTENSIVE ACTION

Investigating the cardiovascular effects of natural compounds, such as linalool, has aroused interest due to the potential impact on cardiovascular health. Linalool, a component present in several essential oils, has demonstrated promising pharmacological properties, including antihypertensive activity. However, its bioavailability and efficacy can be influenced by complexation with β-cyclodextrin, a strategy frequently used to improve the solubility and stability of bioactive substances. This study aimed to carry out a systematic review of the literature, exploring the cardiovascular effects of free linalool and linalool complexed with β-cyclodextrin. Objective: To investigate the cardiovascular effects of free linalool and linalool complexed with β-cyclodextrin, with emphasis on the antihypertensive action, through a systematic review of the literature. Methodology: The review was conducted according to PRISMA guidelines. The PubMed, Scielo and Web of Science databases were consulted, using the descriptors "linalool", "β-cyclodextrin", "cardiovascular effects", "antihypertensive" and "complexation". The inclusion criteria covered studies published in the last 10 years, focusing on in vivo experiments, clinical trials and systematic reviews. Articles unrelated to the topic, duplicate studies and those without peer review were excluded. Results: They revealed that linalool, when complexed with β-cyclodextrin, presented greater bioavailability and stability, enhancing its antihypertensive action. In vivo studies have demonstrated a significant reduction in blood pressure in hypertensive animal models. Furthermore, the complexation positively influenced the gastrointestinal absorption of linalool. These findings suggest that the complexed formulation may represent an effective approach to improving the cardiovascular effects of linalool. Conclusion: The systematic review highlights the relevance of complexing linalool to β-cyclodextrin as a strategy to enhance its antihypertensive effects. Understanding these mechanisms can contribute to the development of more effective pharmaceutical formulations in the management of hypertension, promoting advances in cardiovascular therapy.

Development of an extemporaneous preparation formulation using a simple and non-solubilizing matrix for first in human clinical study

Extemporaneous preparation (EP) formulation is an attractive strategy to accelerate the formulation development of new chemical entities for first entry into human study. In this work, an EP suspension formulation for a development drug candidate GDC-6599 was successfully developed. The formulation spanned a wide concentration range from 0.1 to 2.0 mg/mL. A non-solubilizing vehicle, 0.6 % (w/v) methylcellulose solution was used to suspend GDC-6599. An aversive agent denatonium benzoate at an extremely low level (6 ppm) was applied as a taste masking agent. This enabled a simple matrix for the analysis of related substances from GDC-6599 during all stability studies. Microcrystalline cellulose at 10 mg/mL concentration was added to the EP formulation to generate a suspension appearance, leading to the success of using a single placebo for matching active formulation at all concentrations. The developed formulation demonstrated excellent homogeneity, sufficient stability and passed microbiological enumeration test. Rinsing performance test demonstrated that greater than 99.8 % amount of drug was successfully recovered by rinsing with water twice, providing guidance for clinical dosing. Biopharmaceutical assessment was conducted by both in silico simulation and in vitro tests. Greater than 90 % bioaccessibility of the EP suspension formulation was obtained via an in vitro system mimicking the human gastrointestinal absorption, consistent with the result from the in silico modeling. The developed EP formulation was successfully used to support the early single ascending dose (SAD) cohorts of GDC-6599 Phase I clinical study. The formulation matrix and assessment workflow developed in this work are generalizable as a platform for EP formulation development of new chemical entities for early phase clinical studies.

Impact of κ-Carrageenan on the Cold-Set Pea Protein Isolate Emulsion-Filled Gels: Mechanical Property, Microstructure, and In Vitro Digestive Behavior

More understanding of the relationship among the microstructure, mechanical property, and digestive behavior is essential for the application of emulsion gels in the food industry. In this study, heat-denatured pea protein isolate particles and κ-carrageenan were used to fabricate cold-set emulsion gels induced by CaCl2, and the effect of κ-carrageenan concentration on the gel formation mechanism, microstructure, texture, and digestive properties was investigated. Microstructure analysis obtained by confocal microscopy and scanning electron microscopy revealed that pea protein/κ-carrageenan coupled gel networks formed at the polysaccharide concentration ranged from 0.25% to 0.75%, while the higher κ-carrageenan concentration resulted in the formation of continuous and homogenous κ-carrageenan gel networks comprised of protein enriched microdomains. The hydrophobic interactions and hydrogen bonds played an important role in maintaining the gel structure. The water holding capacity and gel hardness of pea protein emulsion gels increased by 37% and 75 fold, respectively, through increasing κ-carrageenan concentration up to 1.5%. Moreover, in vitro digestion experiments based on the INFOGEST guidelines suggested that the presence of 0.25% κ-carrageenan could promote the digestion of lipids, but the increased κ-carrageenan concentration could delay the lipid and protein hydrolysis under gastrointestinal conditions. These results may provide theoretical guidance for the development of innovative pea protein isolate-based emulsion gel formulations with diverse textures and digestive properties.

Integrated computational and experimental evaluation of phenolic constituents of Apricot fruit L. for antiqourum sensing, antibiofilm, antioxidant, and 15-lox inhibitory properties

The present study investigated the antioxidant profile together with the antibacterial potential of Apricot L. with the aim to find a functional food based anti-infective lead. Additionally the study evaluated the biofilm and QS inhibitory potential of the plant using Pseudomonas aeruginosa (ATCC 15442) and Chromo bacterium Violaceum (DSM 30191) respectively. Several fractions of the peel of Apricot were subjected to initial antimicrobial and antibiofilm screening. Among all the fractions, methanol and ethyl acetate fractions displayed significant antimicrobial activity against the strains selected with MIC values 1.25 mg/dL and 1.68 mg/dL respectively. Similarly, while evaluating antiqourum-sensing potential, methanol extract showed remarkable zone of inhibition (14mm) with Violaceum inhibition (58%) while aqueous part presented moderately good inhibition (32%) with zone of inhibition of (4mm). N-hexane fraction was least active in this regard. In case of free radicals scavenging aptitudes, Ethanolic fraction displayed the highest free radicals scavenging potential (IC50μg/mL 13.76 ± 23.61) while Aqueous and ethyl acetate part exhibited moderate to good antioxidant behaviors with IC50μg/mL of 26.74 ± 22.00 and 19.49 ± 2.91 respectively. Then the selected compounds were screened for putative binding sites and molecular docking studies followed by enzyme inhibition assays. The negative binding energies and close proximity to residues in the binding pocket of selected targets including human α- soybean lox (PDB ID 1IK3), quorum sensing regulators LasR (2UV0) were observed which indicated high affinity and tight binding capacity of compounds 1 and 5 towards the active sites of LasR 2UV0 and 15-lipoxygenase. The physicochemical characteristics and toxicity expectation were computationally accomplished. Bioactivity prediction study revealed that all of the selected Phytoconstituents displayed incredible Bioactivity score. None of the selected chemical compound was found to be toxic as discovered by toxicity studies. Compound 4 exhibited the highest inhibition of 15-lipoxygenase in vitro (69%, at 0.037 mM final concentration) and that is accompanied by compound 5 (60%) whereas in the biofilm inhibition assay, compound 1 was most active (IC50 0.05 mM), followed by compound 3 (IC50 0.07 mM). It was therefore determined that compounds 1 and 3 had the highest biofilm inhibitory activity, whereas compounds 4 and 5 were potent 15-lipoxygenase inhibitors with potentially anti-inflammatory properties. Future investigations are suggested for the characterization and formulation development.

Formulation development and characterization of quercetin loaded poly caprolactone nanoparticles for tumors

Cancer is a formidable health obstacle, characterized by its bleak outlook. Considerable scientific investigation has shed light on the capacity to modify the dispersion of anticancer medications at various levels within tissues and cells by enclosing them within submicronic colloidal systems, often known as nanoparticles. This approach is based on the goal of enhancing the therapeutic effectiveness of these medications while minimizing adverse effects on the entire body. Moreover, the theragnostic characteristics of these nanoparticles are widely acknowledged, hence enhancing their therapeutic potential. The current study is centered on exploring the potential anti-tumor effects of quercetin by utilizing its antioxidant capabilities. The quercetin nanoparticles are synthesized with great precision utilizing the nanoprecipitation approach, in which poly(caprolactone) is utilized as the polymer matrix. Following synthesis, the nanoparticles are extracted for further analysis. Further attempts are undertaken to enhance the drug loading process, and the resultant nanoparticles undergo a thorough analysis, including the examination of their morphology using scanning electron microscopy, and the evaluation of drug-polymer interactions using Fourier transform infrared spectroscopy and differential scanning calorimetry. The remarkable efficacy of quercetin's envelopment can be attributed to its lipophilic nature, reaching a maximum of 81%. The utilization of scanning electron microscopy allows for the observation of nanoparticles with varying forms. Conversely, the absence of noticeable interactions in Fourier-transform infrared analysis indicates the stability of poly(caprolactone) nanoparticles loaded with quercetin.

Remifentanil and Propofol Co-loaded Nanoemulsion: Formulation Development and In vivo Pharmacodynamic Evaluation

Background: The present work is an effort to develop novel propofol (PPF) and remifentanil (RFT) co-loaded nanoemulsion (NME) for the treatment of anesthetic effects. Methods: The PPF/RFT NME was prepared via the high-pressure homogenization method. Its physicochemical properties were assessed to ensure good quality and suitability for i.v. administration. We also studied the in vivo pharmacokinetics and pharmacodynamics of PPF/RFT NME in dogs with an optimized formulation. Results: This study showed that the mean particle size of PPF/RFT NME was 124.2 nm and the zeta potential was −20.6 mV. In the stability test, the NME maintained a good round shape and did not demonstrate any significant changes in physicochemical characteristics. In terms of the in vitro release, the early burst release of the NME preparations containing PPF or RFT was ideal in clinical practice, where a loading dose or a rapid onset of the drug was required. Based on histopathological observations, no histological change occurred to the rat organs after the administration of PPF/RFT NME. Regarding pharmacodynamics, compared with the combination group at the same dose, PPF/RFT NME could make animals enter the anesthetic state faster and the anesthetic effects last longer. In addition, vital signs of PPF/RFT NME could be maintained in a good state while better effects were delivered. Conclusions: This study used PPF and RFT to prepare a compound NME. This could reduce the anesthesiologist's administration time and make the anesthesia process more efficient.

Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques

The availability of analytical methods for the characterization of lipid nanoparticles (LNPs) for in-vivo intracellular delivery of nucleic acids is critical for the fast development of innovative RNA therapies. In this study, analytical protocols to measure (i) chemical composition, (ii) drug loading, (iii) particle size, concentration, and stability as well as (iv) structure and morphology were evaluated and compared based on a comprehensive characterization strategy linking key physical and chemical properties to in-vitro efficacy and toxicity. Furthermore, the measurement protocols were assessed either by testing the reproducibility and robustness of the same technique in different laboratories, or by a correlative approach, comparing measurement results of the same attribute with orthogonal techniques. The characterization strategy and the analytical measurements described here will have an important role during formulation development and in determining robust quality attributes ultimately supporting the quality assessment of these innovative RNA therapeutics.

Effects of Solvent System and Storage Condition on Chemical Stability of 5(alpha)-Reductase Inhibitor Compounds in Tectona grandis L.f. Leaf Extracts

Tectona grandis has been reported for its composition of two 5α-reductase inhibitors, specifically (+)-eperua-8,13-dien-15-oic acid (1) and (+)-eperua-7,13-dien-15-oic acid (2). These compounds exhibit potential as markers, enabling the standardization of leaf extracts during pre-formulation and formulation development. This study examined the effects of solvent system, pH, temperature and light on the stability of compounds 1 and 2 in the ethanolic extract and the ethanolic extract in PG with PEG-40 as a solubilizer. The remaining amount of the compounds at all test conditions was analyzed using HPLC. Compounds 1 and 2 exhibited greater stability in acidic solutions compared to neutral or basic environments. Their degradations were susceptible to light, particularly compound 1 of the ethanolic extract in PG. Both compounds in the solution form of the extract degraded rapidly at high temperature, whereas the present of PG minimized their degradation when the light was protected. According to the Q10 method, the calculated shelf-life of the extracts was 1.48 years. The extracts should be stored or prepared as a non-aqueous form or otherwise in a slightly acidic solution with appropriate light protection measures. The pre-formulation information obtained from this study holds significant value in informing the design and development of forthcoming anti-hair loss medications. HIGHLIGHTS Stability assessment of 5α-reductase inhibitors in teak extracts with solubilizers Shelf life of 2 inhibitors in prepared extracts was predicted using Q10 method This data is useful for the design and development of future anti-hair loss drugs GRAPHICAL ABSTRACT

Formulation Development and Assessment of Solid Dispersion and Hydrotropy for BCS Class II Drug Solubility Enhancement

Aim: This study aimed to evaluate the potential of different hydrophilic polymers to increase Arteether's water solubility. Background: Arteether is classified as a class II biopharmaceutical in the Biopharmaceutical Classification System (BCS), with low water solubility (17 g/mL) and dissolution rate, resulting in poor bioavailability. Objective: The goal of this research is to improve the water solubility of Arteether (ART) by using a solid dispersion and hydrotropic approach with a variety of carriers, such as PEG-6000 PVP K-30, Poloxamer- 188, Poloxamer-407, HPMC E 15LV, HPMC K-100M, sucrose, and mannitol, sodium benzoate, sodium citrate, Urea, nicotinamide, and beta-cyclodextrin. Methods: Melting and evaporation methods were used to make the solid dispersion. Instrumental examinations, including XRD, DSC, FTIR, and SEM, confirmed any physical changes caused by the interaction of ART and carriers. Results: The most significant increase in water solubility of Arteether was discovered with CD: PEG600:Pol -407, and the highest enhancement in solubility was 67 times. While 37.34 times and 49 times increase in solubility was observed at 1:4.3:3.7 weight ratio of AE: PEG-6000:Poloxamer-407 40 percent mix of nicotinamide, respectively. The in vitro results show that ART's dissolution rate in the solid dispersion system was dramatically reduced compared to pure drug. This might be because of the drug's enhanced wettability, dispersion ability, and transition from crystalline to amorphous form. Compared to the ART itself, the permeability of Arteether from solid dispersion was increased up to 7 times. However, the permeability of solid cyclodextrin dispersion was extremely low, just 4.42 times. This may be due to the drug encapsulation in the cyclodextrin cavity. Conclusion: This research successfully developed and optimized various polymer and solubility enhancement approaches for Arteether, resulting in increased water solubility, which may improve Arteether's oral bioavailability. The findings of this study might be utilized to develop an oral dosage of Arteether with enhanced bioavailability.

Preventive Potential of Extracts of Some Dietary Plants against SARSCoV- 2 Infection

Background: Coronavirus disease 2019 (COVID-19) had emerged as an unprecedented global health crisis. The pandemic resulted in over 672 million confirmed cases, and 6.84 million deaths till date. Several dietary plants are known for their beneficial health effects due to their diverse bioactive metabolites. Some of them are already reported for their therapeutic potential against respiratory viral infections with excellent safety profiles. Thus they can serve as sources of bioactive agents for the prevention and treatment of SARS-CoV-2 infection. Objective: With limited therapeutic options, the identification of safe, effective, and affordable medicines for the SARS-CoV-2 infection are urgently needed. The primary aim of the current study is to identify edible plant materials with preventive activity against SARS-CoV-2 infection. Method: Extracts of 30 dietary plants were evaluated for their in cellulo anti-SARS-CoV-2 potential. The antiviral activity was evaluated on SARS-CoV-2, propagated in Vero cell line (ATCCCCL- 81), followed by isolation of viral RNA, and its confirmation by qRT-PCR. Cytotoxicity of extracts was evaluated by using MTT assay in the Vero cell line, while the reduction in viral load was measured through plaque reduction assay. Furthermore, evaluations of the plant extracts on various treatment targets were also performed in cellulo. Results: An extract of Trigonella foenum-graecum L. (Fenugreek leaves) (part of the plant: leaves) was identified as a promising inhibitor of SARS-CoV-2 propagation with 98.7% reduction in the formation of plaques at 50 μg mL−1. Moreover, Trapa natans L. (Water caltrop, fruit) (part of the plant: fruit) also showed a 55.0% reduction in viral load at 50 μg mL−1. Both dietary plants exhibited prophylactic effects against SARS-CoV-2 infection. Conclusion: Trigonella foenum-graecum L., and Trapa natans L. and their bioactive metabolites can be used as preventive agents against SARS-CoV-2 infection. These results can form the basis for the development of anti-viral nutraceutical formulations.

PREFORMULATION STUDIES OF NIOSOMAL GEL CONTAINING DIPIVEFRIN HYDROCHLORIDE FOR ANTIGLAUCOMATIC ACTIVITY

Objective: The present study was focused on developing and characterizing niosomal gel formulations for ocular controlled delivery of an adrenergic agonist; dipivefrin HCl. In the present study, the pre-formulation studies are showed towards the development of Novel formulation. Methods: Preformulation studies of drug were carried out for identification (physical appearance, melting point and UV spectrophotometric analysis), solubility profile, lipophilicity (Partition Coefficient), compatibility studies by FTIR and thermal behavior by DSC. Results: The melting point of dipivefrin HCl was found to be 147.6±3 °C. The log P value was found to be 3.14±0.02, from which it can be interpreted that drug is highly lipophilic in nature. The scanned λmax were found to be 254 nm. No significant changes were found when FTIR spectra of the physical mixture compared with FTIR spectra of pure drug and excipients. This indicates absence of any possible interaction between the drug and excipients which confirms the identity and purity of drug. DSC thermogram of pure drug showed a sharp exothermic peak at 131.202 °C (area=1726.267 mJ, delta H=575.422 J/g), indicating the crystal melting point of the drug. Conclusion: These results suggest that the dipivefrin HCl serve as suitable candidate for ocular drug delivery system.

Assessing Physicochemical Stability of Monoclonal Antibodies in a Simulated Subcutaneous Environment

Monoclonal antibodies (mAbs) are being increasingly administered by the subcutaneous (SC) route compared to the traditional intravenous route. Despite the growing popularity of the subcutaneous route, our current knowledge regarding the intricate mechanistic changes happening in the formulation after injection in the subcutaneous space, as well as the in vivo stability of administered mAbs, remains quite limited. Changes in the protein environment as it transitions from a stabilized, formulated drug product in an appropriate container closure to the SC tissue environment can drastically impact the structural stability and integrity of the injected protein. Interactions of the protein with components of the extracellular matrix can lead to changes in its structure, potentially impacting both safety and efficacy. Investigating protein stability in the SC space can enable early assessment of risk and performance of subcutaneously administered proteins influencing clinical decisions and formulation development strategies. The Subcutaneous Injection Site Simulator (SCISSOR) is a novel in vitro system that mimics the subcutaneous injection site and models the events that a protein goes through as it transitions from a stabilized formulation environment to the dynamic physiological space. In this paper, we utilize the SCISSOR to probe for biophysical and chemical changes in seven mAbs post SC injection using a variety of analytical techniques. After 24 h, all mAbs demonstrated a relative decrease in conformational stability, an increase in fragmentation, and elevated acidic species. Higher order structure analysis revealed a deviation in the secondary structure from the standard and an increase in the number of unordered species. Our findings suggest an overall reduced stability of mAbs after subcutaneous administration. This reduced stability could have a potential impact on safety and efficacy. In vitro systems such as the SCISSOR combined with downstream analyses have potential to provide valuable information for assessing the suitability of lead molecules and aid in formulation design optimized for administration in the intended body compartment, thus improving chances of clinical success.

Predicting the clinical subcutaneous absorption rate constant of monoclonal antibodies using only the primary sequence: a machine learning approach.

Subcutaneous injections are an increasingly prevalent route of administration for delivering biological therapies including monoclonal antibodies (mAbs). Compared with intravenous delivery, subcutaneous injections reduce administration costs, shorten the administration time, and are strongly preferred from a patient experience point of view. An understanding of the absorption process of a mAb from the injection site to the systemic circulation is critical to the process of subcutaneous mAb formulation development. In this study, we built a model to predict the absorption rate constant (ka), which denotes how fast a mAb is absorbed from the site of administration. Once trained, our model (enabled by the XGBoost algorithm in machine learning) can predict the ka of a mAb following a subcutaneous injection using in silico molecular properties alone (generated from the primary sequence). Our model does not need clinically observed plasma concentration-time data; this is a novel capability not previously achieved in predictive pharmacokinetic models. The model also showed improved performance when benchmarked against a recently reported mechanistic model that relied on clinical data to predict subcutaneous absorption of mAbs. We further interpreted the model to understand which molecular properties affect the absorption rate and showed that our findings are consistent with previous studies evaluating subcutaneous absorption through direct experimentation. Taken altogether, this study reports the development, validation, benchmarking, and interpretation of a model that can predict the clinical ka of a mAb using its primary sequence as the only input.

Physical model-based ArF photoresist formulation development

Since the logic 28 nm technology and beyond, ArF immersion lithography has been widely used in manufacturing. To fully utilize the potential of the lithographic resolution, process simulation has been used since the lithography process setup step. The accuracy of the model prediction can be a key factor in the process stability, defectivity, and yield of the final product. To get better model prediction, it is very important to develop a process model with as many parameters as possible with physical meanings. Since the analysis of exposure data with a physical model can provide insights into the process and the photoresist material, it may greatly accelerate the photoresist formulation development or improvement process. From another aspect, as the function of the photoresist is to record the aerial image information on wafer, theoretically, the photoresist image should not deviate much from the aerial image or it will inevitably reduce the information content of the aerial image, i.e., through various kinds of averaging, mixing, etc. Since the emergence of Optical Proximity Correction (OPC), the time that takes to finalize a photolithography process has been significantly lengthened and made more complicated. To make the OPC model more reliable and less dependent on patches, a more physical OPC model is necessary. Therefore, it is clear that if we can develop a photoresist formulation to realize a more physical photoresist image, or a photoresist image closer to the aerial image, we can greatly improve the photolithography process performance and the time consumed for the process setup including OPC. In this paper, we focus on several physical model parameters for photoresist, especially the effective photoacid diffusion length and photo decomposable base parameters. We will show that these two parameters can provide a good description of photoresist imaging behavior, and the resist formulation can be improved to match the physical model prediction with more accuracy.

Oral delivery of the amylin receptor agonist pramlintide

AbstractAmylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico‐chemical compatibility when co‐formulated with insulin. Here, we report the design and characterization of polymeric microparticles for oral delivery of pramlintide. Eudragit S100, a gastric‐resistant polymer, was used in preparation of pramlintide‐loaded spherical microcapsules by double emulsion and solvent evaporation technique, with approximately 66 μm ± 11 particle size, with 83.2% ± 2.7 efficiency for pramlintide entrapment and 67.6% ± 2.1 yield. Intra‐venous pramlintide free in solution showed a plasmatic half‐life of 6.8 min in mice. In contrast, oral delivery of acid‐resistant pramlintide‐loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. Our data provide evidences for the potential use of the oral route in the therapeutic development of pramlintide formulations.

The Effects of Excipients on Freeze-dried Monoclonal Antibody Formulation Degradation and Sub-Visible Particle Formation during Shaking.

We previously reported an unexpected phenomenon that shaking stress could cause more protein degradation in freeze-dried monoclonal antibody (mAb) formulations than liquid ones (J Pharm Sci, 2022, 2134). The main purposes of the present study were to investigate the effects of shaking stress on protein degradation and sub-visible particle (SbVP) formation in freeze-dried mAb formulations, and to analyze the factors influencing protein degradation during production and transportation. The aggregation behavior of mAb-X formulations during production and transportation was simulated by shaking at a rate of 300rpm at 25°C for 24h. The contents of particles and monomers were analyzed by micro-flow imaging, dynamic light scattering, size exclusion chromatography, and ultraviolet - visible (UV-Vis) spectroscopy to compare the protective effects of excipients on the aggregation of mAb-X. Shaking stress could cause protein degradation in freeze-dried mAb-X formulations, while surfactant, appropriate pH, polyol mannitol, and high protein concentration could impact SbVP generation. Water content had little effect on freeze-dried protein degradation during shaking, as far as the water content was controlled in the acceptable range as recommended by mainstream pharmacopoeias (i.e., less than 3%). Shaking stress can reduce the physical stability of freeze-dried mAb formulations, and the addition of surfactants, polyol mannitol, and a high protein concentration have protective effects against the degradation of model mAb formulations induced by shaking stress. The experimental results provide new insight for the development of freeze-dried mAb formulations.

Effect of polysaccharide-protein interactions on the multi-scale structure of hybrid micellar casein-xanthan gum systems

This study reports on the effect of pH and polysaccharide concentration (protein:polysaccharide ratios of 95:5, 85:15 and 75:25) on the interactions established between xanthan gum (XG) and micellar casein (MC), investigating the impact on the type of structures formed at the micro- and nanoscale. At pH ≥ 6, the micellar casein formed stable suspensions where micelles with diameters of ca. 130–150 nm showed a compact inner structure stabilised by colloidal calcium phosphate (CCP) nanoclusters, while at pH ≤ 3, a more loosely packed interconnected network structure, stabilised by protein-protein interactions, was noted. The addition of XG, even at low MC:XG ratios (95:5), resulted in increased stability of the system, preventing the formation of micelle aggregates at the microscale, and reducing the pH range at which casein precipitated close to the isoelectric point. For all the XG loadings, coacervates were formed at pH = 2–3 due to polysaccharide-protein electrostatic interactions, leading to separation into a solid gel-like phase composed of polysaccharide-protein fibrillar structures and a liquid phase rich in protein. At the nanoscale, XG was mostly coating the micelles and filling in the inner water channels when added at MC:XG ratios ≤85:15, while the higher polysaccharide content at the ratio 75:25 allowed to form an interconnected structure. Therefore, by adjusting pH and XG concentration, it is possible to improve casein stability, reduce agglomeration and manipulate the size of protein-polysaccharide complexes formed. This will be of great relevance for the development of novel food formulations with improved stability and modulated sensory and nutritional properties.

Bioavailability of Oral Curcumin in Systematic Reviews: A Methodological Study.

Curcumin is a natural compound found in turmeric that exhibits diverse biological activities. However, its poor bioavailability limits its therapeutic application, which has led to the development of various bioavailability-improved formulations. In this methodological study, we analyzed whether systematic reviews on curcumin considered the bioavailability of systemic oral curcumin formulations when synthesizing evidence from human clinical trials. A total of 171 systematic reviews published between 2003 and 2022 were included in the study. From the included studies, we extracted data on study characteristics; type of curcumin; methods; and reporting regarding bioavailability, funding, and conflict of interest. Our results show that systematic reviews rarely consider the variable bioavailability of tested curcumin formulations. Relevant statistical subgroup and/or sensitivity analyses were reported in the methods and results of only 3.5% and 6.4% of reviews, respectively. However, more reviews mentioned bioavailability in their discussion (57%) or conclusion (13%). The detailed analysis of the included systematic reviews suggests that there is broad recognition of product bioavailability as a crucial factor affecting the health effects of curcumin, which is not accompanied by adequate evidence synthesis. Therefore, the results of most systematic reviews on orally administered curcumin should be taken with caution.

Standardization Quality Control and Development of Poly Herbal Formulation for the Management of Type-2 Diabetes Mellitus

In the Ayurvedic system of medicine, Herbal Drugs For Diabetes Mellitus as mentioned in ancient Indian books like Charak Samhita, Mahdhav Nidan and Astang Sanghra, there are about 600 plants, which are stated to have antidiabetic property Polyherbal antidiabetic formulation consists of six herbs viz., Nigella sativa (seed), Moringa oleifera (seed), Linum usitatissimum (seed), Trogonella foenum (seed), Cinnamum zeylanicum (bark) and Macrotylom auniflorum (seed). Crospovidone, Microcrystalline cellulose, Colloidal Silicon dioxide, PVP Magnesium stearate, (Polyvinyl pyrrolidone). Polyherbal formulation of the extracts of all selected plants was subjected to freeze drying process. The extracts were dried for a period of time according to their rate of drying .Diluents like, Microcrystalline cellulose, Magnesium stearate, Lactose, starch were dried. All active ingredients were weighed according to the formula, mixed with MCC followed by diluents and Glidant like aerosil and magnesium stearate as lubricant as specified in formula were mixed well. The mixture was blended thoroughly for 30minutes. Then the powder was transferred to the polythene bags and labeled for further studies.

Activity of the Di-Substituted Urea-Derived Compound I-17 in Leishmania In Vitro Infections.

Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence associated with the current treatment regimen. In this work, we show that the di-substituted urea-derived compounds I-17 and 3m are effective in inhibiting the promastigote growth of different Leishmania species and reducing the macrophage intracellular load of amastigotes of the Leishmania (L.) amazonensis and L. major species, in addition to exhibiting low macrophage cytotoxicity. We also show a potential immunomodulatory effect of I-17 and 3m in infected macrophages, which exhibited increased expression of inducible Nitric Oxide Synthase (NOS2) and production of Nitric Oxide (NO). Our data indicate that I-17, 3m, and their analogs may be helpful in developing new drugs for treating leishmaniasis.