Poor Solubility Research Articles

Experimental and computational studies on possibility of using glucose diazacrown cryptand as a carrier for anticancer drugs busulfan and lomustine

AbstractDrug carriers play a very important role in pharmacy, especially in cancer therapy. Most drugs used in the treatment of cancer are characterized by poor solubility in water and lack of selectivity in their toxic effects on normal and cancer cells. Administration of the drug in the form of a complex with an appropriately selected carrier can significantly improve its therapeutic effect and reduce side effects. In this study, the possibility of using the cryptand L1, containing two diazacrown ethers and two saccharide groups, as a potential drug carrier is investigated. In order to determine whether it can form complexes with drugs, the cryptand L1 and its complexes with two anticancer drugs, busulfan (BSF) and lomustine (CCNU), were synthesized. Their selected structural and energetic properties were investigated using both experimental and computational methods. Additionally, water solubility and cytotoxicity tests were performed for all compounds. The measured 1H NMR spectra confirm that L1 forms complexes L1:BSF and L1:CCNU, the solubility of which in water appears to be much higher than that of the pure drugs. The results of DFT calculations made in water described with the implicit solvent model confirm high stability of L1:BSF and L1:CCNU and indicate that L1 forms with the drugs mainly non-inclusion complexes. However, additional tests with 20 H2O molecules explicitly included in the model suggest that both inclusion and non-inclusion forms can occur in a real solution. Cytotoxicity studies show that the macrocycle L1 is non-toxic towards both normal and cancer cells, and its complexes with drugs show greater selectivity towards cancer cells. Interestingly, while the cytotoxicity of the L1:BSF complex is stronger than that of pure BSF, the relationship is opposite in the case of L1:CCNU and CCNU. Therefore, L1 can be considered as a potential drug carrier, especially for those drugs that have weak activity on cancer cells.

Improving the Cellular Internalization of Zr(IV) Nanocages by Tuning Hydrophilicity and Lipophilicity

AbstractNanoscale molecular materials have emerged as a new class of compounds at the nanometer scale with well‐defined chemical structures, remarkable uniformity and high reproducibility. Among these materials, zirconium‐based metal‐organic cages (MOCs) have attracted significant attention due to their exceptional stability and applications in catalysis, recognition and separation and so on. However, their poor water solubility impedes their biomedical applications. In this study, decorating the ligand with Ru(II) complexes can not only improve the water solubility but also endow bright red fluorescence with large Stokes shift (180 nm). Notably, butyl‐modification of the cyclopentadiene rings can significantly enhance the cell uptake (100 folds) of nanocages via actin‐ and dynamin‐mediated endocytosis. The unique advantages and easy modifiability of these nanocages make them highly promising candidates for diverse biological applications.

ENHANCING TRANSDERMAL DELIVERY OF POORLY WATER-SOLUBLE NSAIDS: EFFECTIVE STRATEGIES

Transdermal drug delivery offers significant advantages for administering non-steroidal anti-inflammatory drugs (NSAIDs) and anti-complementary drugs, particularly those with poor water solubility. This delivery route bypasses first-pass metabolism and gastrointestinal degradation, enhancing bioavailability and patient compliance. However, the stratum corneum, the outermost layer of the skin, poses a formidable barrier to drug permeation. To address this challenge, several innovative strategies have been developed to improve the transdermal delivery of these poorly soluble drugs. Chemical enhancers, such as alcohols, fatty acids, and surfactants, can disrupt the lipid structure of the stratum corneum, increasing drug solubility and permeability. Nanoformulations, including liposomes, niosomes, solid lipid nanoparticles, and nanoemulsions, enhance drug solubility, provide protection against degradation, and facilitate controlled release with deeper skin penetration. Prodrugs, designed to convert into the active drug within the skin, can improve solubility and permeability. Physical methods like microneedles, iontophoresis, and phonophoresis create micropores or use electrical and ultrasound waves to enhance permeation without compromising skin integrity. Cyclodextrins form inclusion complexes with drugs, boosting solubility and stability. Hydrogels and polymer-based formulations create a moist environment for sustained drug release and better absorption. Co-solvents and surfactants, such as ethanol and DMSO, further enhance solubility and disrupt the stratum corneum to facilitate drug penetration. Electroporation and thermal ablation transiently disrupt the skin barrier, significantly improving drug permeation. These strategies, individually or in combination, hold promise for optimizing the transdermal delivery of poorly water-soluble NSAIDs and anticomplementary drugs, ensuring effective therapeutic outcomes and improved patient compliance.

Biocompatible nanocomposite hydroxyapatite-based granules with increased specific surface area and bioresorbability for bone regenerative medicine applications.

Hydroxyapatite (HA) granules are frequently used in orthopedics and maxillofacial surgeries to fill bone defects and stimulate the regeneration process. Optimal HA granules should have high biocompatibility, high microporosity and/or mesoporosity, and high specific surface area (SSA), which are essential for their bioabsorbability, high bioactivity (ability to form apatite layer on their surfaces) and good osseointegration with the host tissue. Commercially available HA granules that are sintered at high temperatures (≥ 900°C) are biocompatible but show low porosity and SSA (2-5 m2/g), reduced bioactivity, poor solubility and thereby, low bioabsorbability. HA granules of high microporosity and SSA can be produced by applying low sintering temperatures (below 900°C). Nevertheless, although HA sintered at low temperatures shows significantly higher SSA (10-60 m2/g) and improved bioabsorbability, it also exhibits high ion reactivity and cytotoxicity under in vitro conditions. The latter is due to the presence of reaction by-products. Thus, the aim of this study was to fabricate novel biomaterials in the form of granules, composed of hydroxyapatite nanopowder sintered at a high temperature (1100°C) and a biopolymer matrix: chitosan/agarose or chitosan/β-1,3-glucan (curdlan). It was hypothesized that appropriately selected ingredients would ensure high biocompatibility and microstructural properties comparable to HA sintered at low temperatures. Synthesized granules were subjected to the evaluation of their biological, microstructural, physicochemical, and mechanical properties. The obtained results showed that the developed nanocomposite granules were characterized by a lack of cytotoxicity towards both mouse preosteoblasts and normal human fetal osteoblasts, and supported cell adhesion to their surface. Moreover, produced biomaterials had the ability to induce precipitation of apatite crystals after immersion in simulated body fluid, which, combined with high biocompatibility, should ensure good osseointegration after implantation. Additionally, nanocomposite granules possessed microstructural parameters similar to HA sintered at a low temperature (porosity approx. 50%, SSA approx. 30m²/g), Young's modulus (5-8 GPa) comparable to cancellous bone, and high fluid absorption capacity. Moreover, the nanocomposites were prone to biodegradation under the influence of enzymatic solution and in an acidic environment. Additionally, it was noted that the hydroxyapatite nanoparticles remaining after the physicochemical dissolution of the biomaterial were easily phagocytosed by mouse macrophages, mouse preosteoblasts, and normal human fetal osteoblasts (in vitro studies). The obtained materials show great potential as bone tissue implantation biomaterials with improved bioresorbability. The obtained materials show great potential as bone tissue implantation biomaterials with improved bioresorbability.

Standardisation of Curcuminoids into More Bioavailable form (CurcuminAura™) and Its Pharmacokinetics

Curcuminoids are naturally occurring phytocompound extracted from the turmeric rhizome Curcuma longa, a member of the ginger (Zingiberaceae) family. Through the development of a trademark product called Bio-Curcumin, this study seeks to increase the bioavailability and absorption of regular marketed curcumin by 95%. This finding has important implications for the academic and scientific community. The pharmacokinetic study of CurcuminAura™ and its innovation of biocurcuminoids is detailed in detail. Innovation of BioCurcuminoids and its Pharmacokinetic Study of CurcuminAura™ with regular curcuminoids is significantly described which is the need of the hour. This enhanced sunflower lecithin is an effective ingredient in the trademark product CurcuminAuraTM, which was created by Bio-Med Ingredients Pvt.Ltd. Its potency in the market can be increased by lecithin's capacity to efficiently encapsulate active substances, improve bioavailability, and increase absorption. Regular curcumin's weak solubility and poor absorption in its free form. Regular Curcumin due to its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites can greatly limit its utility as a health-promoting agent and dietary supplement. Hence to make it more readily available in the body. CurcuminovaTM is developed will enhance the properties of Curcumin making it more potent in the market. The Evaluation of the Comparative Pharmacokinetic Study of CurcuminAuraTM with Marketed Curcumin 95.0% was carried out through pre-clinical investigations in Sprague Dawley Rats via Oral Route which is the aim of this study with two groups in the study design, with four rats of each sex. Oral administration of CurcuminAuraTM and Curcumin 95.0% was administered to rats in the G1 and G3 groups, respectively. A dosage volume of 10 milliliters per kilogram of body weight was maintained for the oral route. After Dosage, under isofluorane,the blood samples were taken from the retroorbital sinuses after the dose was administered under varying periods of anaesthesia. Animals were split up into two sets for each group, and blood samples were taken at 30-, 2-, and 4-hour intervals. Samples were taken for analysis after being kept at -800C. Designed to increase the bioavailability of curcuminoids, CurcuminAuraTM is standardized to 60.9% total curcuminoids by HPLC, as opposed to marked conventional curcumin 95%. This has been confirmed by HPLC analysis. According to comparison studies, CurcuminAuraTM has a bioavailability that is 3.8 times greater than the reference standard. Additionally, in this study it is shown that the maximum absorption happens in the timeline 3 hrs after feeding the drug.

Production, Characterization, and Application of Hydrophobin-Based IR780 Nanoparticles for Targeted Photothermal Cancer Therapy and Advanced Near-Infrared Imaging.

As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near-infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability. In this study, a genetically engineered dual-functional fusion protein tLyP-1-MGF6 is successfully constructed and expressed, which presents a novel use of hydrophobin MGF6 for its amphiphilicity combined with the tumor-penetrating peptide tLyP-1 to create an innovative carrier for IR780. These results show this fusion protein serving as a biodegradable and biocompatible carrier, significantly improves the water solubility of IR780 when formulated into nanoparticles. These studies demonstrate that the IR780@tLyP-1-MGF6 nanoparticles significantly enhance tumor targeting and photothermal therapeutic efficacy in comparison with control in vitro and in vivo. These advancements highlight the potential of the unique combination hydrophobin-based IR780 delivery system as a multifunctional nanoplatform for integrated imaging and targeted photothermal treatment of breast cancer.

Enhancing Cannabinoid Bioavailability in Pain Management: The Role of Cyclodextrins

Chronic pain (CP), including pain related to cancer, affects approximately 2 billion people worldwide, significantly diminishing quality of life and imposing socio-economic burdens. Current treatments often provide limited relief and may cause adverse effects, demanding more effective alternatives. Natural compounds from Cannabis sativa L., particularly cannabinoids like THC and CBD, exhibit analgesic and anti-inflammatory properties, but their therapeutic use is restricted by poor solubility and low bioavailability. Cyclodextrins (CDs) and cyclic oligosaccharides may encapsulate hydrophobic drugs in order to enhance their solubility and stability, offering a promising solution to these challenges. This study explores the formation of CD inclusion complexes with cannabinoids and specific terpenes, such as D-limonene (LIM), beta-caryophyllene (BCP), and gamma-terpinene (γ-TPN), aiming to improve pharmacokinetic profiles and therapeutic efficacy. We discuss analytical techniques for characterizing these complexes and their mechanisms of action, highlighting the potential of CDs to optimize drug formulations. The integration of CDs in cannabinoid therapies may enhance patient compliance and treatment outcomes in CP management. Future research should focus on innovative formulations and delivery systems to maximize the clinical applications of those compounds.

In-depth analysis of lupeol: delving into the diverse pharmacological profile

Lupeol, a naturally occurring lupane-type pentacyclic triterpenoid, is widely distributed in various edible vegetables, fruits, and medicinal plants. Notably, it is found in high concentrations in plants like Tamarindus indica, Allanblackia monticola, and Emblica officinalis, among others. Quantitative studies have highlighted its presence in Elm bark, Olive fruit, Aloe leaf, Ginseng oil, Mango pulp, and Japanese Pear bark. This compound is synthesized from squalene through the mevalonate pathway and can also be synthetically produced in the lab, addressing challenges in natural product synthesis. Over the past four decades, extensive research has demonstrated lupeol’s multifaceted pharmacological properties, including anti-inflammatory, antioxidant, anticancer, and antibacterial effects. Despite its significant therapeutic potential, clinical applications of lupeol have been limited by its poor water solubility and bioavailability. Recent advancements have focused on nano-based delivery systems to enhance its bioavailability, and the development of various lupeol derivatives has further amplified its bioactivity. This review provides a comprehensive overview of the latest advancements in understanding the pharmacological benefits of lupeol. It also discusses innovative strategies to improve its bioavailability, thereby enhancing its clinical efficacy. The aim is to consolidate current knowledge and stimulate further research into the therapeutic potential of lupeol and its derivatives.

Hot-Melt Extrusion Drug Delivery System-Formulated Haematococcus pluvialis Extracts Regulate Inflammation and Oxidative Stress in Lipopolysaccharide-Stimulated Macrophages

Haematococcus pluvialis contains valuable bioactive compounds, including astaxanthin, proteins, and fatty acids. Astaxanthin is known for its various health benefits, such as preserving the redox balance and reducing inflammation. However, its low stability and poor water solubility present challenges for various applications. Hot-melt extrusion (HME) technology enhances the aqueous solubility of H. pluvialis extracts, increasing the usable astaxanthin content through nanoencapsulation (HME-DDS-applied extracts, ASX-60F and ASX-100F). This study compared the effects of HME-DDS-derived extracts (ASX-60F and ASX-100F) and the non-applied extract (ASX-C) under inflammatory and oxidative stress conditions. In animal models of sepsis, 60F and 100F treatment exhibited higher survival rates and a lower expression of pro-inflammatory biomarkers compared to those treated with C. In lipopolysaccharide-stimulated RAW 264.7 macrophages, nitric oxide (NO) production and the expression of pro-inflammatory mediators such as cyclooxygenase-2 and inducible NO synthase were reduced by 60F or 100F treatments via ERK/p-38 mitogen-activated protein kinase (MAPK) signaling. Moreover, 60F or 100F inhibited reactive oxygen species production regulated by nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Collectively, these findings suggest that HME-DDS-derived H. pluvialis extracts exert anti-inflammatory and antioxidant effects by inhibiting MAPK phosphorylation and activating Nrf2/HO-1 expression.

Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation

Chemotherapy remains the first choice of treatment for colon cancer despite the inevitable adverse effects. Curcumin (CU) possesses antitumor activity but has poor aqueous solubility, low bioavailability, and weak activity. To address this, nine novel monocarbonyl CU analogues were designed, synthesized, and evaluated in the present study. Among them, CA8 exhibited the highest water solubility, which was approximately 2.37 × 106 times that of CU. In addition, compared with CU, its cytotoxicity on Caco-2 cells (19.2 times/48 h) was stronger. Of note, CA8 arrestedthe cell cycle of Caco-2 cells at the G2/M phase and induced apoptosis. Meanwhile, acute toxicity experiments indicated that KM mice tolerated CA8 for up to 300 mg/kg CA8 (oral administration) and 50 mg/kg CA8 (intraperitoneal injection). The oral administration of CA8 to Sprague Dawley rats exhibited higher AUC (0-t) (6.23-fold) and longer MRT (0-t) (3.35-fold) than that of CU. CA8 also inhibited the proliferation and angiogenesis of tumor cells more than CU and tegafur. Finally, CA8 may exert anti-tumor effects through the activation of JNK pathway and inhibition of AKT pathway. These results suggest that CA8 is a safe and highly effective new drug for colon cancer treatment.

Modification of Ceritinib Crystal Morphology via Spherical Crystallization

The formulation process for some drugs can be challenging, due to their unfavorable physical and mechanical properties and poor water solubility. Powder technology has made a significant impact in regard to the modification of the particles in active pharmaceutical ingredients (APIs) to produce high-quality granules. Spherical particles are preferred over other shapes, due to their high tap and bulk density, reduced dustiness, better flowability, strong anti-caking properties, and better mechanical performance during tableting. The present study investigates the possibility of obtaining spherical crystals of ceritinib, a drug used for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer, which belongs to BCS class IV drugs and has a platy crystal structure. Ceritinib spheres were prepared by spherical agglomeration, in a ternary system, and quasi-emulsion solvent diffusion, with the addition of polyvinylpyrrolidone, as well as a combination of these two methods. With the combined method of spherical crystallization, crystals with the most favorable morphology and the narrowest distribution of particle sizes were obtained, which was the reason for further optimization. The influence of different impeller geometries and mixing rates on the morphology of the obtained crystals was examined and the optimal conditions for the process were selected. Using empirical correlations and a visual criterion, the process was scaled up from a 0.1 L to a 1 L batch crystallizer. The obtained crystals were characterized by light and scanning electron microscopy. The addition of a bridging liquid and/or a polymer additive did not change the internal structure of the ceritinib crystals, which was confirmed by X-ray powder diffraction.

Bioavailability enhancement of formononetin by incorporation of natural bioenhancer in phospholipid complex

Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes. Our data showed both groups improved FNT water solubility and oil-water partition coefficient. NMR, DSC, and SEM were performed to identify the interaction and the geometrical nature of complex. When compared, FNT-PIP-PC released more FNT in in vitro release and permeation through Caco-2 monolayer than FNT-PC and pure FNT. In vitro data was consistent with the in vivo pharmacokinetic profile that showed increased, Cmax and AUC(0-24) by 7.16 and 23.33-fold and 29.65 and 23.33-fold at 5 and 10 mg/kg in FNT-PIP-PC, compared to pure FNT. Additionally, co-treatment of PIP and FNT improved in vitro pharmacological action in dexamethasone-induced osteoporosis. Thus, our study showed addition of PIP in FNT-PC further increases FNT water solubility and protects it from phase II metabolism, leading to enhanced bioavailability with improved pharmacological activity.

2D Nano-Photosensitizer Facilitates Proximity Labeling for Living Cells Surfaceome Deciphering.

Photocatalytic proximity labeling has shown great promise for mapping the spatiotemporal dynamics of surfaceome. Although cell-surface targeting photosensitizers relying on antibodies, lipid molecules, and metabolic labeling have gained effects, the development of simpler and stable methods that avoid complex chemical synthesis and biosynthesis steps is still a huge challenge. Here, the study has introduced 2D nanomaterials with the ability of cell surface engineering to perform the in situ anchoring of photosensitizer on living cell surface. Photosensitizer can be stabilized on nanomaterials by coordination after one-step mixing, resulting in the nano-photosensitizer combining cell surface targeting ability and photosensitivity that allowing surface-specific proximity labeling. Nano-photosensitizer can be dispersed stably in aqueous solution, avoiding the defects of poor water solubility and aggregation of traditional organic photosensitizers. Singlet oxygen is generated locally under light irradiation, enabling spatiotemporally-resolved activating and labeling of cell surface proteome. Further application in the brain metastatic lung cancer has been found effective with numerous quantified differential cell surfaces proteins highly correlated with cancer metastasis and three potential players have been validated via immunoblotting and immunofluorescence, providing important insights for metastasis supported molecular mechanism.

Curcumin Derivatives in Medicinal Chemistry: Potential Applications in Cancer Treatment

Curcumin, a naturally occurring compound found in the rhizome of Curcuma plants, particularly in turmeric (Curcuma longa L.), exhibits a broad range of biological activities, including anti-inflammatory, antioxidant, and anticancer properties. Curcumin has demonstrated effectiveness in inhibiting tumor growth, arousing interest for its potential in treating various cancers, such as breast, lung, prostate, and brain cancers. However, the clinical application of curcumin is limited due to its low chemical stability, poor water solubility, and low bioavailability. In response to these challenges, structural modifications of curcumin have been explored to improve its pharmacological properties, including enhanced anticancer selectivity index and bioavailability. This review highlights promising chemical modifications of curcumin that could lead to the development of more effective anticancer therapies. By functionalizing the parent curcumin molecule, researchers aim to create more stable and bioavailable compounds with enhanced therapeutic potential, making curcumin derivatives promising candidates for medical applications.

Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation

The application of ketoconazole (KET) in ocular drug delivery is restricted by its poor aqueous solubility though its broad-spectrum antifungal activity. The aim of this study is to develop an ion-sensitive in situ gel (ISG) of KET to promote its ocular bioavailability in topical application. The solubility of KET in water was increased by complexation with hydroxypropyl-β-cyclodextrin (HPβCD), then KET-HPβCD inclusion complex (KET-IC) was fabricated into an ion-sensitive ISG triggered by sodium alginate (SA). The in vitro drug release and antifungal activities investigations demonstrated that the KET-IC-ISG formulation increased drug release and anti-fungal activities compared to pure KET. The ex vivo rabbit corneal permeation studied demonstrated higher permeability of KET-IC-ISG formulation (Papp of (6.34 ± 0.21) × 10−4 cm/h) than pure KET (Papp of (3.09 ± 0.09) × 10−4 cm/h). The cytotoxicity assay and the ocular irritation study in rabbits confirmed the KET-IC-ISG safety and well tolerance. The ocular pharmacokinetics of KET in rabbits was investigated and the results showed that the KET-IC-ISG increased its bioavailability in cornea by 47-fold. In conclusion, the KET-IC-ISG system promoted the precorneal retention, the ocular drug bioavailability and the developed formulation is a potential strategy to treat mycotic keratitis.

Calcium Transport and Enrichment in Microorganisms: A Review

Calcium is a vital trace element for the human body, and its deficiency can result in a range of pathological conditions, including rickets and osteoporosis. Despite the numerous types of calcium supplements currently available on the market, these products are afflicted with a number of inherent deficiencies, such as low calcium content, poor aqueous solubility, and low human absorption rate. Many microorganisms, particularly beneficial microorganisms, including edible fungi, lactic acid bacteria, and yeast, are capable of absorbing and enriching calcium, a phenomenon that has been widely documented. This opens the door to the potential utilization of microorganisms as novel calcium enrichment carriers. However, the investigation of calcium-rich foods from microorganisms still faces many obstacles, including a poor understanding of calcium metabolic pathways in microorganisms, a relatively low calcium enrichment rate, and the slow growth of strains. Therefore, in order to promote the development of calcium-rich products from microorganisms, this paper provides an overview of the impacts of calcium addition on strain growth, calcium enrichment rate, antioxidant system, and secondary metabolite production. Additionally, it highlights calcium transport and enrichment mechanisms in microorganism cells and offers a detailed account of the progress made on calcium-binding proteins, calcium transport pathways, and calcium storage and release. This paper offers insights for further research on the relevant calcium enrichment in microorganism cells.

Microencapsulation techniques for developing cannabidiol formulations: a review.

Cannabidiol (CBD), extracted from Cannabis sativa L., holds therapeutic promise without inducing psychoactive effects seen with Δ9-tetrahydrocannabinol. Its interaction with the endocannabinoid system plays a pivotal role in regulating mood, pain perception and immune function. Nevertheless, CBD encounters hurdles in clinical application due to its poor bioavailability and water solubility. To overcome these limitations, researchers are exploring microencapsulation techniques, which involve encapsulating CBD within protective matrices. This comprehensive review offers insights into various microencapsulation methods for CBD, scrutinizing their advantages, limitations and implications for formulation optimization. By elucidating the potential of microencapsulation, this review underscores its promise in refining CBD therapy and addressing challenges associated with administration.

Silibinin-Loaded Amphiphilic PLGA–Poloxamer Nanoparticles: Physicochemical Characterization, Release Kinetics, and Bioactivity Evaluation in Lung Cancer Cells

Despite its potential against several carcinomas, the pharmacological efficacy of silibinin (SLB) is hampered by poor solubility, absorption, and oral bioavailability. To face these issues, we developed polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) coated with hydrophilic polyethene oxide (PEO) for controlled and targeted SLB delivery. NPs were produced at two different SLB loadings and presented a spherical shape with smooth surfaces and stable size in water and cell culture medium. The encapsulation efficiencies were found to be >84%, and thermal analysis revealed that the SLB was present in an amorphous state within the NPs. In vitro SLB release experiments revealed that at the lowest SLB loading, desorption of the active molecule from the surface or nanoporosities of the NPs mainly dictates release. In contrast, at the highest SLB loading, diffusion primarily regulates release, with negligible contributions from other mechanisms. Cell experiments showed that, compared with the free drug, SLB loaded in the produced NPs significantly increased the bioactivity against H1299, H1975, and H358 cells.

Non‐Ionic Fluorosurfactants for Droplet‐Based in vivo Applications

AbstractFluorocarbon oils are uniquely suited for many biomedical applications due to their inert, bioorthogonal properties. In order to interface fluorocarbon oils with biological systems, non‐ionic fluorosurfactants are necessary. However, there is a paucity of non‐ionic fluorosurfactants with low interfacial tension (IFT) to stabilize fluorocarbon phases in aqueous environments (such as oil‐in‐water emulsions). We developed non‐ionic fluorosurfactants composed of a polyethylene glycol (PEG) segment covalently bonded to a flexible perfluoropolyether (PFPE) segment that confer low IFTs between a fluorocarbon oil (HFE‐7700) and water. The synthesis of a panel of surfactants spanning a molecular weight range of 0.64–66 kDa with various hydrophilic‐lipophilic balances allowed for identification of minimal IFTs, ranging from 1.4 to 17.8 mN m−1. The majority of these custom fluorosurfactants display poor solubility in water, allowing their co‐introduction with fluorocarbon oils and minimal leaching. We applied the PEG5PFPE1 surfactant for mechanical force measurements in zebrafish, enabling exceptional sensitivity.

Novel Pharmaceutical Cocrystal Consisting of Chlorzoxazone and Nicotinamide: A New Promising Carrier for Solubility Augmentation.

Chlorzoxazone (CHZ) is a centrally acting muscle relaxant used to treat muscle spasms. It is employed as a first-line medication for treating muscle spasms, offering both musculoskeletal relaxation and mild sedative effects. According to the biopharmaceutics classification system, it belongs to class II drug having poor solubility and high permeability. In order to improve the flow property, water solubility, and dissolution of CHZ, CHZ-nicotinamide (NA) cocrystal was prepared by liquid-assisted grinding cocrystallization (LAG CC) method using methanol as the choice of solvent. CHZ-NA cocrystal was characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry, and scanning electron microscopy (SEM). DSC scan showed a sharp endothermic peak shift, which is caused by the formation of a new crystal form with altered physical properties, which was further confirmed by PXRD. Also, a change in the surface morphology of LAG CC compared to CHZ was observed in SEM. The resultant CHZ-NA cocrystal displayed improved powder flow properties compared to the native form of CHZ. LAG CC demonstrated a 3.1- and 2.6-fold increase in saturated solubility and intrinsic dissolution rate, respectively, compared to CHZ alone. Furthermore, the in vitro dissolution study showed that the cumulative dissolution of CHZ in 2 h was about 53%. Whereas, dissolution of LAG CC reached 99% in 2 h, showing obvious dissolution improvement. Thus, CHZ-NA cocrystal could significantly improve the flow properties, solubility and dissolution of CHZ.