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Biomaterials Apr 2024In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is...
In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.
Topics: Animals; Rabbits; Carcinoma, Hepatocellular; Liver Neoplasms; Nanovaccines; Chemoembolization, Therapeutic; Hypoxia; Tumor Microenvironment
PubMed: 38271787
DOI: 10.1016/j.biomaterials.2024.122480 -
Food Chemistry Oct 2023In this study, tomato sauces were prepared by adding different levels of emulsified oil (0, 5, 10, or 20 wt%) to tomato pomace. The effects of adding these excipient...
In this study, tomato sauces were prepared by adding different levels of emulsified oil (0, 5, 10, or 20 wt%) to tomato pomace. The effects of adding these excipient emulsions on the concentration, bioaccessibility, and bioactivity of the carotenoids and phenolics in the tomato sauces were then determined. The carotenoid and phenolic profiles were analyzed by HPLC and LC-MS/MS, respectively. The bioaccessibility values of the lycopene, lutein, and β-carotene were around 36-82%, 73-112%, and 67-94% for tomato sauces with excipient emulsions, respectively. In contrast, they were considerably lower for tomato sauces without excipient emulsions, being around 24-31%, 69-71%, and 45-62%, respectively. The TPC and TAC values of the tomato sauces with the excipient emulsions were significantly higher than those without. Considerably higher concentrations of carotenoids and phenolic compounds were detected in the tomato sauce samples containing the excipient emulsions. These results suggest that the presence of the oil droplets increased the extractability, stability, and bioaccessibility of the nutraceuticals in the tomato sauce.
Topics: Antioxidants; Emulsions; Excipients; Solanum lycopersicum; Chromatography, Liquid; Biological Availability; Tandem Mass Spectrometry; Carotenoids; Phenols
PubMed: 37263092
DOI: 10.1016/j.foodchem.2023.136395 -
AAPS PharmSciTech Feb 2024Pulmonary drug delivery is a form of local targeting to the lungs in patients with respiratory disorders like cystic fibrosis, pulmonary arterial hypertension (PAH),... (Review)
Review
Pulmonary drug delivery is a form of local targeting to the lungs in patients with respiratory disorders like cystic fibrosis, pulmonary arterial hypertension (PAH), asthma, chronic pulmonary infections, and lung cancer. In addition, noninvasive pulmonary delivery also presents an attractive alternative to systemically administered therapeutics, not only for localized respiratory disorders but also for systemic absorption. Pulmonary delivery offers the advantages of a relatively low dose, low incidence of systemic side effects, and rapid onset of action for some drugs compared to other systemic administration routes. While promising, inhaled delivery of therapeutics is often complex owing to factors encompassing mechanical barriers, chemical barriers, selection of inhalation device, and limited choice of dosage form excipients. There are very few excipients that are approved by the FDA for use in developing inhaled drug products. Depending upon the dosage form, and inhalation devices such as pMDIs, DPIs, and nebulizers, different excipients can be used to provide physical and chemical stability and to deliver the dose efficiently to the lungs. This review article focuses on discussing a variety of excipients that have been used in novel inhaled dosage forms as well as inhalation devices.
Topics: Humans; Excipients; Administration, Inhalation; Nebulizers and Vaporizers; Asthma; Lung; Pharmaceutical Preparations
PubMed: 38356031
DOI: 10.1208/s12249-024-02741-w -
International Journal of Biological... Dec 2023Starch is a natural, renewable, affordable, and easily available polymer used as gelling agents, thickeners, binders, and potential raw materials in various food... (Review)
Review
Starch is a natural, renewable, affordable, and easily available polymer used as gelling agents, thickeners, binders, and potential raw materials in various food products. Due to these techno-functional properties of starch, food and non-food industries are showing interest in developing starch-based food products such as films, hydrogels, starch nanoparticles, and many more. However, the application of native starch is limited due to its shortcomings. To overcome these problems, modification of starch is necessary. Various single and dual modification processes are used to improve techno-functional, morphological, and microstructural properties, film-forming capacity, and resistant starch. This review paper provides a comprehensive and critical understanding of physical, chemical, enzymatic, and dual modifications (combination of any two single modifications), the effects of parameters on modification, and their applications. The sequence of modification plays a key role in the dual modification process. All single modification methods modify the physicochemical properties, crystallinity, and emulsion properties, but some shortcomings such as lower thermal, acidic, and shear stability limit their application in industries. Dual modification has been introduced to overcome these limitations and maximize the effectiveness of single modification.
Topics: Starch; Excipients; Resistant Starch
PubMed: 37722643
DOI: 10.1016/j.ijbiomac.2023.126952 -
BioMed Research International 2023Binders are ingredients used in tablet granulation process for tablet cohesiveness which confirms that the tablet remains intact after compression. Natural gums have...
Binders are ingredients used in tablet granulation process for tablet cohesiveness which confirms that the tablet remains intact after compression. Natural gums have been employed as disintegrants, emulsifying agents, suspending agents, and binders in tablets. Even though gum is claimed as a possible pharmaceutical excipient by some phytochemical studies, literature is scanty on its efficacy as a tablet binder. The purpose of this study was to isolate, characterize, and comparatively evaluate gum as a potential binder in tablet formulation. Gum was extracted from tree, characterized for physicochemical properties, and applied as a binder in paracetamol granule and tablet formulation. Granules were prepared using 4%, 6%, 8%, and 10% w/w concentration of the gum and standard binders (polyvinylpyrrolidone K-30 and Starch1500) by wet granulation. The formulated tablets were then evaluated for tablet quality parameters, and comparison between the test and standard binders was done by ANOVA. The dried crude gum yielded 50.63% (w/w) of a brownish yellow purified gum. The angle of repose, Carr's index, and the Hausner ratio all complied with the pharmacopoeial recommendations. The gum is compatible with the model drug, paracetamol. The paracetamol granules prepared with gum binder demonstrated an optimum size range and size distribution with substantial flow and compressibility properties. gum binder demonstrated significantly higher disintegration time and strength properties than that of similar concentrations of Starch1500 but lower than polyvinylpyrrolidone ( < 0.05). gum has better binding properties than starch but lower than polyvinylpyrrolidone. Hence, gum can be used as an alternative tablet binder in tablet manufacturing.
Topics: Excipients; Ficus; Acetaminophen; Povidone; Starch; Tablets
PubMed: 37593524
DOI: 10.1155/2023/8852784 -
PDA Journal of Pharmaceutical Science... Feb 2024Compared to glass prefilled syringes (PFSs), cyclic olefin polymer (COP) PFS showed more consistent and predictable extrusion forces when exposed to a variety of...
Compared to glass prefilled syringes (PFSs), cyclic olefin polymer (COP) PFS showed more consistent and predictable extrusion forces when exposed to a variety of excipient combinations (buffers, tonicity agents, and surfactants) at various accelerated storage conditions. Furthermore, COP PFSs also showed significantly less variance in extrusion forces within each individual stroke, which is critical for precision applications. Observed performance differences can be explained by fundamental differences in the stability and homogeneity of the primary packaging materials (i.e., COP vs siliconized glass) and their physicochemical interactions with excipients.
Topics: Polymers; Excipients; Syringes; Glass; Drug Packaging; Silicone Oils
PubMed: 37714568
DOI: 10.5731/pdajpst.2022.012760 -
International Journal of Pharmaceutics Jul 2023Thermal conductivity and specific heat capacity are two important parameters for the drying process of pharmaceutical materials during methods such as wet granulation...
Thermal conductivity and specific heat capacity are two important parameters for the drying process of pharmaceutical materials during methods such as wet granulation that can be observed in the overall tablet manufacturing process. In this study, a transient line heat source method was used for the first time to determine the thermal conductivity and volumetric specific heat capacity of common pharmaceutical components and binary mixtures, with moisture content ranging from 0 % to 30 % w.b and active ingredient loading between 0 % and 50 % by weight. A three-parameter least squares regression model relating the thermal properties to moisture content and porosity was evaluated at a 95 % confidence interval, with R values ranging from 0.832 to 0.997. Relationships were established between thermal conductivity, volumetric specific heat capacity, porosity, and moisture content for pharmaceutical ingredients including acetaminophen, microcrystalline cellulose, and lactose monohydrate.
Topics: Hot Temperature; Powders; Porosity; Thermal Conductivity; Excipients; Tablets; Drug Compounding; Water
PubMed: 37331643
DOI: 10.1016/j.ijpharm.2023.123130 -
Clinical Infectious Diseases : An... Nov 2023Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process...
Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process monitoring and control of critical process parameters that affect product quality attributes. Chemistry, Manufacturing, and Controls (CMC) for both upstream (USP) and downstream processes (DSP) need mapping of critical process parameters (CPP) and linking these to critical quality attributes (CQA) to ensure quality and consistency of phage drug substance (DS) and DPs development. Single-use technologies are increasingly becoming the go-to manufacturing option with benefits both for phage bioprocess development at the engineering run research stage and for final manufacture of the phage DS. Future phage DPs under clinical development will benefit from implementation of process analytical technologies (PAT) for better process monitoring and control. These are increasingly being used to improve process robustness (to reduce batch-to-batch variability) and productivity (yielding high phage titers). Precise delivery of stable phage DPs that are suitably formulated as liquids, gels, solid-oral dosage forms, and so forth, could significantly enhance efficacy of phage therapy outcomes. Pre-clinical development of phage DPs must include at an early stage of development, considerations for their formulation including their characterization of physiochemical properties (size, charge, etc.), buffer pH and osmolality, compatibility with regulatory approved excipients, storage stability (packaging, temperature, humidity, etc.), ease of application, patient compliance, ease of manufacturability using scalable manufacturing unit operations, cost, and regulatory requirements.
Topics: Humans; Bacteriophages; Pharmaceutical Preparations; Excipients
PubMed: 37932112
DOI: 10.1093/cid/ciad555 -
Journal of Drugs in Dermatology : JDD Sep 2023Age-related changes in body skin are emerging as important therapeutic targets. A novel topical firming and toning body lotion (FTB) has been developed to target... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Age-related changes in body skin are emerging as important therapeutic targets. A novel topical firming and toning body lotion (FTB) has been developed to target multiple pathways involved in body skin rejuvenation.
METHODS
FTB was evaluated in a randomized, double-blind, vehicle-controlled, 12-week study in women (N=54) with mild to moderate lack of firmness on the upper arms and mild to moderate cellulite on the thighs. Investigator clinical assessments, instrumentation evaluations, and patient questionnaires were performed. Histological assessment of ex vivo human skin treated with FTB and gene expression analysis in 3-dimensional human skin models following application of FTB or product comparators were conducted.
RESULTS
At week 12, FTB treatment significantly improved (vs baseline) firmness, sagging, smoothness, texture, cellulite, and crepiness on investigator-, instrument-, and photographically assessed outcomes. Participants reported significant improvements in self-perceived efficacy and overall satisfaction with the appearance of their skin following FTB treatment vs vehicle control. Adverse events were mild or moderate in severity. FTB supported new collagen and elastic fiber formation in ex vivo skin. FTB increased skin rejuvenation–associated gene expression vs comparator products.
CONCLUSIONS
FTB provided significant improvements in the upper arms and thighs compared with baseline and vehicle control across multiple investigator and instrumentation evaluations. Most participants reported greater efficacy and treatment satisfaction with FTB vs vehicle. FTB treatment stimulated dermal extracellular matrix renewal and induced expression of genes involved in skin rejuvenation pathways. This study provides clinical and preclinical evidence supporting the use of FTB to improve body skin quality. Citation: Makino ET, Jiang LI, Acevedo SF, et al. Restoration of aging body skin: evidence-based development of a topical formulation for improving body skin quality. J Drugs Dermatol. 2023;22(9):887-897. doi:10.36849/JDD.7292.
Topics: Humans; Female; Cellulite; Skin; Rejuvenation; Upper Extremity; Excipients; Aging
PubMed: 37683065
DOI: 10.36849/JDD.7292 -
International Journal of Pharmaceutics May 2024Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better...
Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better understanding drug release rates from particles; however, this has been an analytical challenge due to the small particle size (from a few micrometers down to nanometers) and the complex composition of the formulations. Here, we employ nano-thermal analysis (nanoTA) to probe the nanothermal domain of a pharmaceutical aerosol formulation containing a mixture of fluticasone propionate (FP), salmeterol xinafoate (SX), and excipient lactose, which is widely used to treat asthma and chronic obstructive pulmonary disease (COPD). Furthermore, atomic force microscopy-infrared spectroscopy (AFM-IR) and AFM force measurements are performed to provide nanochemical and nanomechanical information to complement the nanothermal data. The colocalized thermal and chemical mapping clearly reveals the surface heterogeneity of the drugs in the aerosol particles and demonstrates the contribution of the surface chemical composition to the variation in the thermal properties of the particles. We present a powerful analytical approach for in-depth characterization of thermal/chemical/morphological properties of dry powder inhaler particles at micro- and nanometer scales. This approach can be used to facilitate the comparison between generics and reference inhalation products and further the development of high-performance pharmaceutical formulations.
Topics: Aerosols; Powders; Fluticasone; Salmeterol Xinafoate; Particle Size; Lactose; Dry Powder Inhalers; Microscopy, Atomic Force; Excipients; Administration, Inhalation; Bronchodilator Agents; Spectrophotometry, Infrared; Chemistry, Pharmaceutical; Surface Properties
PubMed: 38615803
DOI: 10.1016/j.ijpharm.2024.124116