Drug Formulations Research Articles

15N Hyperpolarization of Metronidazole Antibiotic in Aqueous Media Using Phase-Separated Signal Amplification by Reversible Exchange with Parahydrogen.

Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [15N3]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15N sites achieved in less than 2 min. The 15N polarization T1 of ∼12 min is reported for the 15NO2 group at the clinically relevant field of 1.4 T in the aqueous phase, demonstrating a remarkably long lifetime of the hyperpolarized state. The produced aqueous solution of [15N3]metronidazole that contained only ∼100 μM of residual Ir was deemed biocompatible via validation through the MTT colorimetric test for assessing cell metabolic activity using human embryotic kidney HEK293T cells. This low-cost and ultrafast hyperpolarization procedure represents a major advance for the production of a biocompatible HP [15N3]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.

Carbon nanotubes conjugated with cisplatin activate different apoptosis signaling pathways in 2D and 3D-spheroid triple-negative breast cancer cell cultures: a comparative study.

The type of experimental model for the in vitro testing of drug formulations efficiency represents an important tool in cancer biology, with great attention being granted to three-dimensional (3D) cultures as these offer a closer approximation of the clinical sensitivity of drugs. In this study, the effects induced by carboxyl-functionalized single-walled carbon nanotubes complexed with cisplatin (SWCNT-COOH-CDDP) and free components (SWCNT-COOH and CDDP) were compared between conventional 2D- and 3D-spheroid cultures of human breast cancer cells. The 2D and 3D breast cancer cultures were exposed to various doses of SWCNT-COOH (0.25-2μg/mL), CDDP (0.158-1.26μg/mL) and the same doses of SWNCT-COOH-CDDP complex for 24 and 48h. The anti-tumor activity, including modulation of cell viability, oxidative stress, proliferation, apoptosis, and invasion potential, was explored by spectrophotometric and fluorometric methods, immunoblotting, optical and fluorescence microscopy. The SWCNT-COOH-CDDP complex proved to have high anti-cancer efficiency on 2D and 3D cultures by inhibiting cell proliferation and activating cell death. A dose of 0.632μg/mL complex triggered different pathways of apoptosis in 2D and 3D cultures, by intrinsic, extrinsic, and reticulum endoplasmic pathways. Overall, the 2D cultures showed higher susceptibility to the action of complex compared to 3D cultures and SWCNT-COOH-CDDP proved enhanced anti-tumoral activity compared to free CDDP.

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis.

Fluconazole (FNL) is one of the first-line treatments for fungal keratitis as it is an effective broad-spectrum antimicrobial commonly administered orally or topically. However, FNL has a very low water solubility, limiting its drug formulation, therapeutic application, and bioavailability through tissues. To overcome these limitations, this study aimed to develop FNL inclusion complexes (FNL-IC) with cyclodextrin (α-cyclodextrin, sulfobutylether-β-cyclodextrin, and hydroxypropyl-γ cyclodextrin) and incorporate it into a dissolvable microneedle (DMN) system to improve solubility and drug penetration. FNL-IC was evaluated for saturation solubility, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release, minimum inhibitory concentration, minimum fungicidal concentration, and time-killing assay. DMN-FNL-IC was evaluated for mechanical and insertion properties, surface pH, moisture absorption ability, water vapor transmission, and drug content recovery. Moreover, ocular kinetic, ex vivo antimicrobial, in vivo antifungal, and chorioallantoic membrane (HET-CAM) assays were conducted to assess the overall performance of the formulation. Mechanical strength and insertion properties revealed that DMN-FNL-IC has great mechanical and insertion properties. The in vitro release of FNL-IC was significantly improved, exhibiting a 9-fold increase compared to pure FNL. The ex vivo antifungal activity showed significant inhibition of Candida albicans from 6.54 to 0.73 log cfu/mL or 100-0.94%. In vivo numbers of colonies of 0.87 ± 0.13 log cfu/mL (F2), 4.76 ± 0.26 log cfu/mL (FNL eye drops), 3.89 ± 0.24 log cfu/mL (FNL ointments), and 8.04 ± 0.58 log cfu/mL (control) showed the effectiveness of DMN preparations against other standard commercial preparations. The HET-CAM assay showed that DMN-FNL-IC (F2) did not show any vascular damage. Finally, a combination of FNL-IC and DMN was developed appropriately for ocular delivery of FNL, which was safe and increased the effectiveness of treatments for fungal keratitis.

A micro-fabricated potentiometric platform with application in a COVID-19 drug quantification and the determination of its binding affinity to a supramolecular host

Recent applications in host–guest chemistry include advanced sensing technologies, drug formulations, and drug delivery. Quantification of host–guest binding constants is significant to the continued optimization of their use. Binding constants offer valuable information about the stability and affinity of the formedcomplex that is essential to both drug formulations and delivery. In this study a novel green, portable, disposable, and cost-efficient microfabricated potentiometric sensor is introduced and successfully applied to determine the concentration of remdesivir (RMD), a COVID-19 drug, and its binding affinity to the supramolecular host sulfobutylether-β-cyclodextrin (SBEβCD) as a compatible solubilizing agent; to overcome the low water solubility of RMD which presents a significant challenge in its intravenous administration. The sensor incorporates multi-walled carbon nanotubes to improve stability and detection limits. To reduce interference effects and enhance the selectivity of the sensor for RMD, 4-tert-butyl-calix[8]arene was employed as an ionophore. A Nernstian potentiometric response for RMD over a concentration range of 1.0 × 10−3 to 1.0 × 10−6 M with a slope of 58.2 ± 0.9 mV decade−1 and a detection limit of 0.23 µM were achieved. The binding constant of the RMD-SBEβCD complex was determined to be 9.76 × 103 M−1. The proposed sensor was shown to be effective for drug quantification and measurements of binding affinities, providing valuable insights into the physicochemical properties of target drugs.

PH/ Temperature/ Redox and Light-responsive Polymersome Structure and Application in Cancer Therapy: Smart Drug Delivery and Targeted Drug Release.

Improvements in cancer treatment are largely influenced by more people knowing about it and developing new ways to diagnose and treat it. New methods such as nanotheranostics and the use of tiny particles have greatly improved the diagnosis, control and treatment of cancer. They have also helped overcome problems with traditional treatments. Nanotheranostics contribute to personalized medicine by helping doctors choose the right treatment, track how well the treatment works, and plan future treatments. Polymers have many advantages as smart or durable drug formulations among small therapeutic platforms. These small sacks, which can be used for drug delivery and imaging, are not harmful to natural tissues and are becoming more popular. Scientists have found a special group of tiny particles made of polymers that can carry active ingredients. These particles show the potential of creating a useful platform for the diagnosis and treatment of diseases on a very small scale. In the past ten years, people have become more interested in polymersomes. They have been used for various medical purposes, such as controlling blood sugar, treating cancer and fighting bacteria. Polymers are stronger and more stable than liposomes. Biocompatible and biodegradable polymers are very important for faster translation and creation of useful medical formulations. Recent progress in this field includes the creation of intelligent, centralized and responsive containers. In this review, we will examine and provide information about polymersomes. We will discuss their properties and how they can be used as drug delivery systems.

From Conventional to Cutting-Edge: A Comprehensive Review on Drug Delivery Systems

Abstract: The essential need for efficacious conveyance of therapeutics to specific tissues or cells, refinement of drug formulations, and the scalability of industrial production drives the pre-sent-day demand for enhanced drug delivery systems (DDS). Newly devised drugs often exhibit suboptimal biopharmaceutical properties, resulting in diminished patient adherence and adverse side effects. The paramount importance of site-specific drug delivery lies in its capacity to facili-tate the targeted administration of diverse therapeutic agents, catering to both localized ailments and systemic treatments. Alongside targeted drug delivery strategies encompassing ligand-based targeting and stimuli-responsive systems, the advent of cutting-edge nanotechnologies such as nanoparticles, liposomes, and micelles has marked a paradigm shift. Additionally, personalized medicines have emerged as a consequential facet of drug delivery, emphasizing the customization of treatment approaches. Researchers have explored an excess of methodologies in the advance-ment of these formulation technologies, including stimuli-responsive drug delivery, 3D printing, gene delivery, and various other innovative approaches. This comprehensive review aims to pro-vide a holistic understanding of the past, present, and future of drug delivery systems, offering in-sights into the transformative potential of emerging technologies.

A four-in-one multifunctional self-assembly hydrogel composed of natural drugs for repairing myocardial infarction

To meet the multiple demands of myocardial repair, it would be a novel strategy for myocardial repair if multiple drugs could be constructed into an integrated multifunctional drug formulation. In this study, four drugs with different functions (thioctic acid with antioxidant effects, quercetin with anti-inflammatory and antioxidant effects, arginine with pro-angiogenic effects, and Mn2+ with imaging functions) were selected to construct a four-in-one injectable hydrogel (thioctic acid-arginine-quercetin-Mn2+) through chemical bonding and supramolecular interactions. First, thioctic acid polymerized to a redox-sensitive degradable polymer—poly(thioctic acid) containing disulfide bonds in the main chains through ring-opening polymerization. Quercetin was conjugated to the main chain of the poly(thioctic acid) molecules via thiyl radical-polyphenol Michael addition. Arginine cross-linked the carboxyl groups side chains of the poly(thioctic acid) molecules through hydrogen bonding. Mn2+ further cross-linked the carboxyl groups' side chains of the poly(thioctic acid) molecules through ionic bonding. The hydrogel has antioxidant properties, promotes neovascularization, inhibits inflammatory, improves intracellular Ca2+ overload and mitochondrial dysfunction, protects adenosine triphosphatase (ATPase) activity, and maintains intracellular energy supply, which can reduce the size of myocardial infarcts, and improves cardiac function. This construction method of preparing integrated multifunctional hydrogels from natural drugs will provide a new therapeutic strategy for myocardial repair.

Perfluorodecalin allows resuspension and prevents sediment solidification of extended-release drug formulations in primary packaging.

In this technical note we show with two simple experiments how Perfluorodecalin (PFD), an injectable perfluorocarbon, can be used as an agent for resuspending microparticulate suspensions in primary packaging containers for injection. Furthermore, we explain how this can be a substantial improvement regarding patient compliance in comparison to the commonly used gas headspace for resuspension. Our experiments are conducted with poly(lactic-co-glycolic acid) particles (often used in extended-release pharmaceutical formulations for injection) and in primary packaging that is commonly used in injection devices (glass cartridges). The results show that our method is feasible for resuspension and moreover even sediment solidification/caking is reduced. The differences between the two datasets collected are statistically significant with p < 0.01 in both cases.

A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution

Despite the widespread use of polymers as precipitation inhibitors in supersaturating drug formulations, the current understanding of their mechanisms of action is still incomplete. Specifically, the role of hydrophobic drug interactions with polymers by considering possible supramolecular conformations in aqueous dispersion is an interesting topic. Accordingly, this study investigated the tendency of polymers to create hydrophobic domains, where lipophilic compounds may nest to support drug solubilisation and supersaturation. Fluorescence spectroscopy with the environment-sensitive probe pyrene was compared with atomistic molecular dynamics simulations of the model drug fenofibrate (FENO). Subsequently, kinetic drug supersaturation and thermodynamic solubility experiments were conducted. As a result, the different polymers showed hydrophobic domain formation to a varying degree and the molecular simulations supported interpretation of fluorescence spectroscopy data. Molecular insights were gained into the conformational structure of how the polymers interacted with FENO in solution phase, which apart from nucleation and crystal growth effects, determined drug concentrations in solution. Notable was that even at the lowest polymer concentration of 0.01 %, w/v, there were polymer-specific solubilisation effects of FENO observed and the resulting reduction in apparent drug supersaturation provided relevant knowledge both from a mechanistic and practical perspective.

Cardiovascular adverse events associated with antibody-drug conjugates (ADCs): a pharmacovigilance study based on the FAERS database

ObjectiveAs a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events.Research design and methodsWe used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated.ResultsIn the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged &amp;lt;18 years, 18–64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure (n = 277) and embolic and thrombotic events, venous (n = 446) were the most frequently reported CVD-related AEs in ADCs.ConclusionBy mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality.

Tumor-On-A-Chip Models for Predicting In Vivo Nanoparticle Behavior.

Nanosized drug formulations are broadly explored for the improvement of cancer therapy. Prediction of in vivo nanoparticle (NP) behavior, however, is challenging, given the complexity of the tumor and its microenvironment. Microfluidic tumor-on-a-chip models are gaining popularity for the in vitro testing of nanoparticle targeting under conditions that simulate the 3D tumor (microenvironment). In this review, following a description of the tumor microenvironment (TME), the state of the art regarding tumor-on-a-chip models for investigating nanoparticle delivery to solid tumors is summarized. The models are classified based on the degree of compartmentalization (single/multi-compartment) and cell composition (tumor only/tumor microenvironment). The physiological relevance of the models is critically evaluated. Overall, microfluidic tumor-on-a-chip models greatly improve the simulation of the TMEin comparison to 2D tissue cultures and static 3D spheroid models and contribute to the understanding of nanoparticle behavior. Interestingly, two interrelated aspects have received little attention so far which are the presence and potential impact of a protein corona as well as nanoparticle uptake through phagocytosing cells. A better understanding of their relevance for the predictive capacity of tumor-on-a-chip systems and development of best practices will be a next step for the further refinement of advanced in vitro tumor models.

Dessecting the Toxicological Profile of Polysorbate 80 (PS80): Comparative Analysis of Constituent Variability and Biological Impact Using a Zebrafish Model

Polysorbate 80, commonly abbreviated as PS80, is a widely used pharmaceutical excipient renowned for its role as a solubilizer and stabilizer in drug formulations. Although PS80 is essential for various pharmaceutical applications, particularly in the formulation of injectable drugs, it has been implicated in a range of adverse reactions. However, due to the complexity of the composition of PS80, the differences in the types and contents of the constituents of PS80 from different manufacturers increase the probability or likelihood of their uneven quality.Addressing the complete spectrum of PS80′s components is challenging; thus, most studies to date have examined PS80 as a singular entity. This approach, however, carries a degree of uncertainty, as it overlooks the unique composition and concentration of components within the PS80 used in experiments, which may not reflect the actual diversity in commercially available PS80 products.Recognizing the critical need to understand how PS80′s composition influences biological effects and toxicity, our study aims to bridge this knowledge gap. By doing so, we can clarify how different PS80 compositions from various manufacturers might affect the quality of pharmaceutical formulations, and also guide excipient manufacturers toward producing higher-quality PS80. Such insights could further facilitate a more targeted application of PS80 in drug development.Building on our previous work, we isolated and prepared two key components of PS80—polyoxyethylene sorbitan monooleate (PSM) and polyoxyethylene isosorbide monooleate (PIM)—and conducted a systematic comparison. We evaluated the acute, hemolytic, and target organ toxicity of two different PS80 samples, as well as PSM and PIM, using a zebrafish model. Our research also delved into the potential mechanisms behind the observed toxicological effects, providing an in-depth understanding of PS80′s impact on biological systems.The results show that PS80, PSM, and PIM resulted in developmental anomalies in larval zebrafish. The primary organs of acute toxicity in zebrafish exposed to PS80 and its typical components PSM and PIM include the cardiovascular system, kidneys, intestines, skin, and liver. Notably, PIM further induced severe pericardial edema and erythrocyte hemolysis, thereby affecting blood flow. The samples also instigated oxidative damage by disrupting the redox equilibrium in the larvae. Compared to PS80, both PSM and PIM induced greater oxidative damage, with PIM notably causing significantly higher lipid oxidation, suggesting that oxidative stress may play a crucial role in polysorbate80-induced toxicity. Furthermore, our study found that PS80 could induce alterations in DNA conformation. The findings underscore the necessity for excipient regulators to establish comprehensive quality standards for Polysorbate 80 (PS80). By implementing such standards, it is possible to minimize the clinical risks associated with the variability in PS80 composition, ensuring safer pharmaceutical products for patients.

DESIGN AND DEVELOPMENT OF NANOEMULSION OF SMILAX CHINA FOR ANTI-PSORIASIS ACTIVITY

DESIGN AND DEVELOPMENT OF NANOEMULSION OF SMILAX CHINA FOR ANTI-PSORIASIS ACTIVITY

Fabrication and evaluation of stable amorphous polymer-drug composite particles via a nozzle-free ultrasonic nebulizer

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs–Empagliflozin, Furosemide, and Ilaprazole–are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.

Synthon Approach in Crystal Engineering to Modulate Physicochemical Properties in Organic Salts of Chlorpropamide.

The formulation of drug with improved bioavailability is always challenging and indispensable in the field of pharmaceutics. The control of intermolecular interactions via crystal engineering approach and solid-state molecular recognition results in the formation of active drug molecules with modulated pharmacological benefits. Therefore, with the aim to improve the solubility and dissolution rate of the drug chlorpropamide (CPA), the mechanochemical liquid-assisted grinding (LAG) of the drug with several pharmaceutically accepted excipients was performed. This contributed to the discovery of six novel solid phases, namely salts, salt cocrystals and salt cocrystal hydrate─the salt of CPA with 3, 4-diaminopyridine (DAP); salt and salt cocrystal (SC) polymorph (Z″=3) with 1, 4-diazabicyclo [2.2.2] octane (DABCO); a salt, SC polymorph (Z″=9), and a SC hydrate (Z″=9) with piperazine (PIP). The formation of these salts and salt cocrystals are mainly guided by the strong hydrogen bonds with tunable strength having high electrostatic contribution. This attractive interaction brings the donor and the acceptor atoms close to each other for a facile proton transfer. Furthermore, the conformational constraints on the drug molecules, provided by the excipients via strong and directional hydrogen bonds, are quite impressive as this leads to the identification and characterization of "new conformational isomers" for the CPA molecules. The new crystalline phases exhibit enhanced intrinsic dissolution rate in comparison to that of the pure drug, the magnitude being 7, 131, and 120 folds for CPADAP, CPADABCO_II, and CPAPIP_III, respectively. Furthermore, it is interesting to note that the order of solubility is enhanced by 2.7-, 3-, and 7-fold, respectively, for the abovementioned salts. This also mirrors the trends in the magnitude of the binding energy, the higher magnitude being reflected in the lower solubility. Additionally, the in vivo experiments performed in SD rats results in the enhancement of the magnitude of the pharmacokinetic properties, when compared to the pristine drug. The concentration of the drug in CPADABCO_II and CPAPIP_III formulations exhibits 6- and 4-fold increments, respectively. Indeed, these results corroborate to the trends observed in the structural characterization, intermolecular energy calculations, solubility, and in vitro dissolution assessments.

Characterization of new hydrophilic polymers obtained from co-processed Detarium microcarpum seed gum with acacia, guar and tragacanth gums

This work was aimed at developing and characterizing new hydrophilic polymers obtained through co-processing of Detarium microcarpum seed gum (DMG) with acacia (ACG), guar (GGG) and tragacanth (TGG) gums respectively. The hydrophilic polymer obtained from the seed of Detarium microcarpum (DT) was co-processed with acacia, guar and tragacanth gums respectively in proportions of 5%DMG+95%ACG, 10%DMG+90%ACG, 15%DMG+85%ACG, and 20%DMG+80%ACG. Replicate co-processed powders of DMG+GGG and DMG+TGG were prepared. The co-processed powders were characterized for: densities (bulk density, tapped density and particle density), flow parameters (flow rate, angle of repose, Hausner’s quotient, Carr’s index and porosity), moisture properties (hydration capacity, swelling index, moisture content and moisture absorption), viscosity and pH respectively using standard methods. The results obtained showed that the densities of the polymers increased at all the concentrations they were co-processed. However, not all the co-processed polymers had a good flow. Moisture studies showed improved hydrophilic properties for all the co-processed polymers with regards to the swelling index and hydration capacities. The viscosities of the composite co-processed polymers also increased as the concentrations of the co-processed gums increased. Co­processing of acacia, guar and tragacanth gums with D. microcarpum seed gum enhanced the swelling index, hydration capacities and viscosities of these gums. This demonstrates that the new hydrophilic polymers obtained from the co-processing can be used as good suspending, disintegrating and binding agents when properly applied in drug formulations.

Nanotechnology for Pain Management.

Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches.

β-Glucan Extraction from Hull-Less Barley by a Novel Approach: Microwave-Assisted Pressurized CO2/H2O

AbstractΒ-glucans (BGs) are dietary fibers with human health benefits. Due to their emulsifying, thickening, and water-holding properties, they are frequently utilized in food formulations. Hull-less barley is one of the important sources of BGs. This research was performed to extract BGs from hull-less barley using microwave-assisted pressurized CO2/H2O (MW-PCO2) extraction, a combination that had never been employed before. The MW-PCO2 extraction conditions (temperature, time and water: barley flour ratio) were optimized using response surface methodology (RSM) with a Box-Behnken design for the maximum BG yield (%). Temperature of 47.74 °C, time of 19.92 min, and water: barley flour ratio of 10.10:1 (g/g) were found to be the optimum conditions for extraction with a BG yield of 62.43%. Additionally, MW-PCO2 extraction was compared with conventional water extraction (CE) and BG extracts obtained by both methods were characterized. Chemical composition, molecular weight, thermal properties, water solubility, water holding capacity, surface morphology, and Fourier Transform Infrared Spectrum (FTIR) of the BG extracts were determined. MW-PCO2 extraction gave higher BG yield and purity, molecular weight, and water holding capacity using less solvent in a shorter time. Furthermore, both extracts have similar morphological images, FTIR spectrum, and thermal properties. The results of this work demonstrate the potential of the MW-PCO2 approach for extracting BGs from hull-less barley with improved selectivity and recovery, which can then be added to a variety of food and drug formulations.

The pharmacist's role in optimizing medication management before, during, and after minimally invasive and bariatric surgery.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Minimally invasive surgery (MIS) with integrated enhanced recovery pathways (ERPs) helps reduce length of stay and improve surgical outcomes. As these procedures have become more prevalent over time, pharmacists are in key positions to manage medications in the perioperative space to help optimize transitions of care and reduce safety events. Here we identify several clinical areas across phases of care for these procedures in which the knowledge and guidance of pharmacists, as members of the interprofessional team, are paramount. Perioperative pharmacy expertise is often required for MIS procedures in the areas of acid suppression, antithrombotic management, blood glucose control, drug formulation, immunosuppressant optimization, pain mitigation, and postoperative nausea and vomiting prevention and treatment. For each MIS procedure, pharmacists should identify and consider diet and anatomical changes as well as patient- and surgery-specific risk factors. Pharmacists can then utilize their knowledge of the pharmacokinetics and pharmacodynamics of individual medications along with evidence-based medicine to recommend selection of appropriate agents. Pharmacist contributions to perioperative medication management for MIS procedures can improve care as surgical patients navigate transitions through the perioperative setting. Pharmacists can further incorporate medication expertise through development and implementation of institutional MIS protocols within the context of ERPs. As such, any pharmacist should feel empowered to aid in the care of surgical patients.

Exploring the Potential of Momordica charantia Fruits Mucilage as a Novel Pharmaceutical Excipient

Background: The discovery and developments of new drug formulations are inspired by medicinal plants. Polysaccharides, such as mucilage or gum from medicinal plants, have a variety of physicochemical properties and are commonly used in pharmaceutical applications. Objectives: The current study's objectives are to construct and assess Metformin HCl tablets employing Momordica charantia (MC) natural mucilage as a binder and release modifier. Methods: The mucilage was isolated from the fruits of MC. The tablet was made using a wet granulation process, and the formulation included several mucilage ratios (1%, 2.5%, 5%, and 10%). Results: It was found that the granules and tablets had good flow qualities based on results of the pre- and post-compression parameters. The release kinetic study showed that F4 showed the first order release kinetics and F8 showed the zero and the higuchi’s release kinetics. In low concentration of mucilage tablets showed good binding properties with immediate release properties. As the concentration was increased, tablets showed good binding properties with sustained release properties. Conclusion: The isolated mucilage from Momordica charantias has the potential to be used as a tablet binder and as an intermediary in the development of a sustained-release drug