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International Journal of Molecular... Oct 2022To improve liposomes' usage as drug delivery vehicles, cryoprotectants can be utilized to prevent constituent leakage and liposome instability. Cryoprotective agents... (Review)
Review
To improve liposomes' usage as drug delivery vehicles, cryoprotectants can be utilized to prevent constituent leakage and liposome instability. Cryoprotective agents (CPAs) or cryoprotectants can protect liposomes from the mechanical stress of ice by vitrifying at a specific temperature, which forms a glassy matrix. The majority of studies on cryoprotectants demonstrate that as the concentration of the cryoprotectant is increased, the liposomal stability improves, resulting in decreased aggregation. The effectiveness of CPAs in maintaining liposome stability in the aqueous state essentially depends on a complex interaction between protectants and bilayer composition. Furthermore, different types of CPAs have distinct effective mechanisms of action; therefore, the combination of several cryoprotectants may be beneficial and novel attributed to the synergistic actions of the CPAs. In this review, we discuss the use of liposomes as drug delivery vehicles, phospholipid-CPA interactions, their thermotropic behavior during freezing, types of CPA and their mechanism for preventing leakage of drugs from liposomes.
Topics: Cryoprotective Agents; Liposomes; Ice; Freezing; Excipients; Phospholipids
PubMed: 36293340
DOI: 10.3390/ijms232012487 -
Lignin as a Natural Carrier for the Efficient Delivery of Bioactive Compounds: From Waste to Health.Molecules (Basel, Switzerland) Jun 2022Lignin is a fascinating aromatic biopolymer with high valorization potentiality. Besides its extensive value in the biorefinery context, as a renewable source of... (Review)
Review
Lignin is a fascinating aromatic biopolymer with high valorization potentiality. Besides its extensive value in the biorefinery context, as a renewable source of aromatics lignin is currently under evaluation for its huge potential in biomedical applications. Besides the specific antioxidant and antimicrobial activities of lignin, that depend on its source and isolation procedure, remarkable progress has been made, over the last five years, in the isolation, functionalization and modification of lignin and lignin-derived compounds to use as carriers for biologically active substances. The aim of this review is to summarize the current state of the art in the field of lignin-based carrier systems, highlighting the most important results. Furthermore, the possibilities and constraints related to the physico-chemical properties of the lignin source will be reviewed herein as well as the modifications and processing required to make lignin suitable for the loading and release of active compounds.
Topics: Antioxidants; Excipients; Lignin
PubMed: 35684534
DOI: 10.3390/molecules27113598 -
Proceedings of the National Academy of... Jul 2021The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health...
The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.
Topics: Adhesives; Administration, Inhalation; Angiotensin-Converting Enzyme 2; Animals; COVID-19; Cryoprotective Agents; Drug Storage; Epithelial Cells; Excipients; HEK293 Cells; Humans; Hyaluronic Acid; Lung; Mice; Mice, Transgenic; Nanostructures; SARS-CoV-2; Virus Attachment
PubMed: 34292870
DOI: 10.1073/pnas.2102957118 -
International Journal of Pharmaceutics Dec 2022The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40...
The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.
Topics: Male; Female; Rats; Animals; Excipients; Biological Availability; Polysorbates; ATP Binding Cassette Transporter, Subfamily G, Member 2; Ranitidine; Poloxamer; Rats, Wistar; Neoplasm Proteins; Estradiol; Testosterone
PubMed: 36336203
DOI: 10.1016/j.ijpharm.2022.122365 -
Polimery W Medycynie 2022Irvingia gabonensis kernel polymer has gained attention in drug delivery systems because of its compatibility and degradation under natural and physiological conditions.
BACKGROUND
Irvingia gabonensis kernel polymer has gained attention in drug delivery systems because of its compatibility and degradation under natural and physiological conditions.
OBJECTIVES
This study aimed to evaluate Irvingia gabonensis polymer as a matrix system for the controlled delivery of ibuprofen in comparison to xanthan gum and hydroxypropylmethylcellulose (HPMC).
MATERIAL AND METHODS
Irvingia gabonensis polymer was extracted using established methods and dried using the ovenand freeze-drying methods. Ibuprofen tablets were prepared by direct compression and the effects of polymer concentration (10-50%), excipients (lactose, microcrystalline cellulose and dicalcium phosphate dihydrate) and polymers (xanthan gum and HPMC) on the mechanical and drug release properties of the tablets were evaluated. Density measurements and the Heckel and Kawakita equations were used to determine the compression properties of the tablets. Friability, crushing strength and the crushing strength-friability ratio (CSFR) were used to evaluate the mechanical properties of the tablets, while dissolution times were used to evaluate drug release from the matrices. The drug release mechanisms were determined by fitting the dissolution data into classic kinetic equations.
RESULTS
Irvingia gabonensis polymer deformed plastically with a fast onset and a high amount of plastic deformation compared with xanthan gum and HPMC. This polymer was directly compressible and formed intact non-disintegrating tablets; the mechanical and dissolution properties of Irvingia gabonensis polymer tablets generally decreased with increasing concentration of ibuprofen. The ranking of dissolution times was xanthan gum > freeze-dried Irvingia gabonensis > HPMC > oven-dried Irvingia gabonensis. The addition of the excipients improved the mechanical properties of the tablets, aided ibuprofen release, and altered the release kinetics, which was largely defined by the Korsmeyer-Peppas model. Increasing the proportion of xanthan gum and HPMC in the matrices resulted in a decreased amount of ibuprofen released after 9 h, with xanthan gum having a greater effect.
CONCLUSIONS
Irvingia gabonensis polymer matrices may be effective in the preparation of controlled release tablets, and their right combination with xanthan gum or HPMC could provide a time-independent release for longer durations.
Topics: Ibuprofen; Polymers; Excipients; Drug Delivery Systems; Hypromellose Derivatives; Tablets; Delayed-Action Preparations; Solubility
PubMed: 36268745
DOI: 10.17219/pim/153521 -
Actas Dermo-sifiliograficas Apr 2021The administration of appropriate doses of active ingredients and excipients is crucial for achieving desired treatment outcomes in pediatric dermatology. A number of... (Review)
Review
The administration of appropriate doses of active ingredients and excipients is crucial for achieving desired treatment outcomes in pediatric dermatology. A number of factors need to be considered, including the characteristics of the lesion, the patient, and the drug. An additional challenge in pediatric settings is the limited number of commercially available formulations suitable for use in children. Drug compounding, which is the preparation of medications tailored to the needs of individual patients, is a good alternative for pediatric populations for a number of reasons. Using a customized compound, the clinician can prescribe formulations that contain the optimal dose of the active ingredients within acceptable limits and the most suitable vehicle and formulation components. Compounding can also be used to combine several active ingredients in a single medication and even adapt the vehicle to the characteristics of the lesion and the needs of the patient. The pharmaceutical formulations described in this review are based on extensive clinical experience and can be customized to meet individual needs.
Topics: Adaptation, Physiological; Child; Dermatology; Drug Compounding; Excipients; Humans; Pharmaceutical Preparations
PubMed: 33220314
DOI: 10.1016/j.ad.2020.11.006 -
Opportunities for milk and milk-related systems as 'new' low-cost excipient drug delivery materials.Advanced Drug Delivery Reviews Apr 2022Milk is well recognised as an amazing delivery system for essential lipids, poorly soluble nutrients, sugars, amino acids and delivery of critical biological molecules... (Review)
Review
Milk is well recognised as an amazing delivery system for essential lipids, poorly soluble nutrients, sugars, amino acids and delivery of critical biological molecules to sustain the infant and adult alike. It is also a safe and abundant resource with potential to act as a low-cost material for formulation of medicines, especially for paediatric patients and those in low economy settings. However, its use in low cost formulations has never developed beyond preclinical evaluation. Reasons for this are several-fold including variable composition and therefore regulatory challenges, as well as a lack of clear understanding around when milk or milk-related materials like infant formula could best be deployed by linking drug properties with excipient composition attributes, especially when taking digestion into account. This review collects the current understanding around these issues. It is apparent from the evolving understanding that while milk may be a bridge too far for translation as an excipient, infant formula is positioned to play a key role in the future because, as a powder-based excipient, it has the performance benefits of milk powder together with the controlled specifications during manufacture and versatility of application to function as a low cost lipid excipient to enable potential translation for the oral delivery of poorly water soluble drugs for key populations including paediatrics and low economy medicines.
Topics: Adult; Animals; Child; Drug Delivery Systems; Excipients; Humans; Milk; Pharmaceutical Preparations; Powders; Solubility
PubMed: 35143892
DOI: 10.1016/j.addr.2022.114139 -
Pharmaceutical Research Jul 2020The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials....
PURPOSE
The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spray-drying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spray-drying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas. The product dries rapidly to form a powder, but small amounts of residual solvent (typically, 1 to 10 wt%) remain in the product and must be removed in a secondary-drying process. For some spray-dried materials, secondary drying by traditional techniques can take days and requires balancing stability risks with process time.
METHODS
Spray-dried polymers were secondary dried, comparing the results for three state-of-the-art methods that employed a jacketed, agitated-vessel dryer: (1) vacuum-only drying, (2) water-assisted drying, or (3) methanol-assisted drying. Samples of material were pulled at various time points and analyzed by gas chromatography (GC) and Karl Fischer (KF) titration to track the drying process.
RESULTS
Model systems were chosen for which secondary drying is slow. For all cases studied, methanol-assisted drying outperformed the vacuum-only and water-assisted drying methods.
CONCLUSIONS
The observation that methanol-assisted drying is more effective than the other drying techniques is consistent with the free-volume theory of solvent diffusion in polymers.
Topics: Chromatography, Gas; Desiccation; Drug Compounding; Excipients; Kinetics; Mass Spectrometry; Methanol; Polymers; Powders; Solubility; Solvents; Volatile Organic Compounds; Water
PubMed: 32737611
DOI: 10.1007/s11095-020-02890-0 -
Scientific Reports Jun 2023This study demonstrates a full-color near-eye holographic display capable of superimposing color virtual scenes with 2D, 3D, and multiple objects with extended depth...
This study demonstrates a full-color near-eye holographic display capable of superimposing color virtual scenes with 2D, 3D, and multiple objects with extended depth upon a real scene, which also has the ability to present different 3D information depending on the focus of the user's eyes using a single computer-generated hologram per color channel. Our setup makes use of a hologram generation method based on two-step propagation and the singular value decomposition of the Fresnel transform impulse response function to efficiently generate the holograms of the target scene. Then, we test our proposal by implementing a holographic display that makes use of a phase-only spatial light modulator and time-division multiplexing for color reproduction. We demonstrate the superior quality and computation speed of this approach compared with other hologram generation techniques with both numerical and experimental results.
Topics: Augmented Reality; Eye; Excipients; Eye Color; Holography
PubMed: 37391489
DOI: 10.1038/s41598-023-36128-x -
Pharmaceutical Research Dec 2021
Topics: Chemistry, Pharmaceutical; Excipients
PubMed: 34931284
DOI: 10.1007/s11095-021-03157-y