Taiwan Chingguan Yihau may improve post-COVID-19 respiratory complications through PI3K/AKT, HIF-1, and TNF signaling pathways revealed by network pharmacology analysis.

The emergence of new SARS-CoV-2 variants with a higher contagious capability and faster transmissible speed has imposed an incessant menace on global health and the economy. The SARS-CoV-2 infection might reoccur and last much longer than expected. Thence, there is a high possibility that COVID-19 can cause long-term health problems.

Oral Delivery of Photopolymerizable Nanogels Loaded with Gemcitabine for Pancreatic Cancer Therapy: Formulation Design, and in vitro and in vivo Evaluations.

Background: Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for pancreatic ductal adenocarcinoma (PDAC).

Differential cellular responses to FDA-approved nanomedicines: an exploration of albumin-based nanocarriers and liposomes in protein corona formation.

Albumin nanoparticles (NPs) and PEGylated liposomes have garnered tremendous interest as therapeutic drug carriers due to their unique physicochemical properties. These unique properties also have significant effects on the composition and structure of the protein corona formed around these NPs in a biological environment. Herein, protein corona formation on albumin NPs and liposomes was simultaneously evaluated through and simulation studies.

A physiologically-based pharmacokinetic model for predicting doxorubicin disposition in multiple tissue levels and quantitative toxicity assessment.

Doxorubicin is a widely-used chemotherapeutic drug, however its high toxicity poses a significant challenge for its clinical use. To address this issue, a physiologically-based pharmacokinetic (PBPK) model was implemented to quantitatively assess doxorubicin toxicity at cellular scale. Due to its unique pharmacokinetic behavior (e.

Application of Design of Experiments in the Development of Self-Microemulsifying Drug Delivery Systems.

Oral delivery has become the route of choice among all other types of drug administrations. However, typical chronic disease drugs are often poorly water-soluble, have low dissolution rates, and undergo first-pass metabolism, ultimately leading to low bioavailability and lack of efficacy. The lipid-based formulation offers tremendous benefits of using versatile excipients and has great compatibility with all types of dosage forms.

Synergistic Combination of Irinotecan and Rapamycin Orally Delivered by Nanoemulsion for Enhancing Therapeutic Efficacy of Pancreatic Cancer.

In recent years, combining different types of therapy has emerged as an advanced strategy for cancer treatment. In these combination therapies, oral delivery of anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (SNENP) and evaluated its synergistic combination effects on pancreatic cancer.

Combined Docetaxel/Pictilisib-Loaded mPEGylated Nanocarriers with Dual HER2 Targeting Antibodies for Synergistic Chemotherapy of Breast Cancer.

Introduction: Approximately 15%~30% of breast cancers have gene amplification or overexpression of the human epidermal growth factor receptor 2 (HER2), resulting in the chemotherapy resistance, a more-aggressive phenotype and poor prognosis.

Methods: We propose a strategy of nanocarriers co-loaded with docetaxel (DTX) and pictilisib (PIC) at a synergistic ratio and non-covalently bound with dual anti-HER2 epitopes bispecific antibodies (BsAbs: anti-HER2-IV/methoxy-polyethylene glycol (mPEG) and anti-HER2-II/methoxy-PEG) for synergistic targeting to overcome the therapeutic dilemmas of the resistance for HER2-targetable chemodrugs. DTX/PIC-loaded nanocarriers (D/P_NCs) were prepared with single emulsion methods and characterized using dynamic light scattering analysis, and the drug content was assayed by high-performance liquid chromatographic method.

Formulation Development of Doxycycline-Loaded Lipid Nanocarriers using Microfluidics by QbD Approach.

Liposomes have been used to improve therapeutic efficacy of drugs by increasing their bioavailability and altering biodistribution. The loading capacity of small molecules in liposomes remains a critical issue. Besides, the manufacturing process of liposomes requires multi-step procedures which hinders the clinical development.

Investigation of the discriminatory ability of analytes for the bioequivalence assessment of ezetimibe: Parent drug, metabolite, total form, and combination of parent drug and total form.

The analysis of parent drug is usually the design of choice for a bioequivalence (BE) study. However, there is a controversy regarding the choice of analytes between EMA and USFDA for the BE study of ezetimibe (EZE). The EMA recommends measuring the total form alone, that means the sum of the concentration of "parent" EZE and "metabolite" ezetimibe-glucuronide (EZEG), as the BE determination.

Oleic Acid-Based Self Micro-Emulsifying Delivery System for Enhancing Antifungal Activities of Clotrimazole.

Due to the increasing rate of drug resistance in spp., higher doses of antifungal agents are being used resulting in toxicity. Drug delivery systems have been shown to provide an effective approach to enhance the efficacy and reduce the toxicity of antifungal agents.

Installation of Pargyline, a LSD1 Inhibitor, in the HDAC Inhibitory Template Culminated in the Identification of a Tractable Antiprostate Cancer Agent.

Pragmatic insertion of pargyline, a LSD1 inhibitor, as a surface recognition part in the HDAC inhibitory pharmacophore was planned in pursuit of furnishing potent antiprostate cancer agents. Resultantly, compound elicited magnificent cell growth inhibitory effects against the PC-3 and DU-145 cell lines and led to remarkable suppression of tumor growth in human prostate PC-3 and DU-145 xenograft nude mouse models. The outcome of the enzymatic assays ascertained that the substantial antiproliferative effects of compound were mediated through HDAC6 isoform inhibition as well as selective MAO-A and LSD1 inhibition.

Optimization and Development of Selective Histone Deacetylase Inhibitor (MPT0B291)-Loaded Albumin Nanoparticles for Anticancer Therapy.

Histone deacetylase (HDAC) inhibitors have emerged as a new class of antitumor agent for various types of tumors. MPT0B291, a novel selective inhibitor of HDAC6, demonstrated significant antiproliferative activity in various human cancer cell types. However, MPT0B291 has very low water solubility, which limits its clinical use for cancer therapy.

CPT11 with P-glycoprotein/CYP 3A4 dual-function inhibitor by self-nanoemulsifying nanoemulsion combined with gastroretentive technology to enhance the oral bioavailability and therapeutic efficacy against pancreatic adenocarcinomas.

Therapeutic efficacies of orally administrated hydrophobic chemodrugs are decreased by poor water solubilities and reduced oral bioavailabilities by P-glycoprotein (P-gp) and CYP450. In this study, CPT11 alone or combined with dual-function inhibitors (baicalein (BA) silymarin (SM), glycyrrhizic acid (GA), and glycyrrhetinic acid (GLA)) of P-gp and CYP450 loaded in a lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENP) to improve the solubility and inhibit the elimination by P-gp and CYP450. Results revealed that the LBSNENP composed of Capryol 90, lecithin/Tween 80/Cremophor EL, and propylene glycol at a weight ratio of 18:58:24 (designated PC90C10P0) was optimally selected.

Fabrication and characterization of Rhizochitosan and its incorporation with platelet concentrates to promote wound healing.

Composite dressing composed of Rhizochitosan and Regenplex™ to promote wound healing were assessed. Rhizochitosan was fabricated by deacetylation of Rhizochitin, which obtained by simply depigmenting sporangium-free mycelial mattress produced from Rhizopus stolonifer F6. Physicochemical characterizations of Rhizochitosan demonstrated that it contained 13.

Pragmatic recruitment of memantine as the capping group for the design of HDAC inhibitors: A preliminary attempt to unravel the enigma of glioblastoma.

Hurdled and marred by the notorious nature of glioblastomas (GBM) in terms of resistance to therapy and limited drug delivery into the brain, the anti-GBM drug pipeline is required to be loaded with mechanistically diverse agents. The consideration of HDAC inhibition as a prudent approach to circumvent the resistance issue in GBM spurred us to pragmatically design and synthesizes hydroxamic acids endowed with CNS penetrating ability. By virtue of the blood brain barrier permeability (BBB), memantine was envisioned as an appropriate CAP component for the construction of the HDAC inhibitors.

Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (MPMs) for Improving Solubility to Enhance Oral Bioavailability.

Objective: This study was intended to utilize lecithin-based mixed polymeric micelles (MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.

Methods: Lecithin was selected to increase the volume of the core of MPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor and Pluronic series) were included with lecithin for screening and optimization.

One-pot fabrication of sacchachitin for production of TEMPO-oxidized sacchachitin nanofibers (TOSCNFs) utilized as scaffolds to enhance bone regeneration.

One-pot fabrication of sacchachitin (SC) for mass-production was developed and optimized by selecting KOH as alkaline agent in depigmentation step and utilizing NaClO as bleaching agent in subsequent step in the same pot. Overall yield of one-pot-fabricated SC was up to 35 %w/w of initial weight with a fibrous texture soft enough for mechanical disintegration into SC nanofibers (SCNFs) and better dispersion for producing TEMPO-oxidized SCNFs (T033SC). Both SCNFs and T033SC could form a 3D gelatinous scaffold into which MC3T3-E1 cells were attracted.

A Novel Composite Hydrogel Composed of Formic Acid-Decellularized Pepsin-Soluble Extracellular Matrix Hydrogel and Sacchachitin Hydrogel as Wound Dressing to Synergistically Accelerate Diabetic Wound Healing.

Extracellular matrix (ECM) hydrogel can create a favorable regenerative microenvironment and act as a promising dressing for accelerating the healing of diabetic wound. In this study, a simple and effective decellularization technique was developed and optimized to obtain acellular extracellular matrix (ECM) from porcine skin. It was found that decellularization at 30% formic acid for 72 h effectively decellularized porcine skin while retaining >75% collagen and ~37% GAG in the ECM with no presence of nuclei of cellular remnants.

Ocular Disease Therapeutics: Design and Delivery of Drugs for Diseases of the Eye.

The ocular drug discovery field has evidenced significant advancement in the past decade. The FDA approvals of Rhopressa, Vyzulta, and Roclatan for glaucoma, Brolucizumab for wet age-related macular degeneration (wet AMD), Luxturna for retinitis pigmentosa, Dextenza (0.4 mg dexamethasone intracanalicular insert) for ocular inflammation, ReSure sealant to seal corneal incisions, and Lifitegrast for dry eye represent some of the major developments in the field of ocular therapeutics.

Ultrasound-assisted synthesis of thermosensitive nanovesicle for direct trap and release of analgesic drugs in biofluid and sewage.

An environmentally friendly thermosensitive nanovesicle-cloud point microextraction technique has been developed with the assistant of ultrasonic waves to determine analgesic drugs with a broad range of polarity in field water and human urine. Based on thin-film hydration, the conformation of nanovesicles formed by a binary mixing system with the nonionic surfactants was evaluated using regular and cryogenic transmission electron microscopy. The multilayered nano-spherical structure was able to capture polar and nonpolar compounds simultaneously.

Lecithin-Stabilized Polymeric Micelles (LPMs) for Delivering Quercetin: Pharmacokinetic Studies and Therapeutic Effects of Quercetin Alone and in Combination with Doxorubicin.

In this study, lecithin-stabilized polymeric micelles (LPMs) were prepared to load quercetin (QUE) in order to improve its bioavailability and increase its antitumor activity. Its combination with doxorubicin (DOX) to minimize DOX-mediated cardiac toxicity and increase the antitumor activity of QUE-loaded LPMs was also examined. LPMs were prepared following a previously reported procedure.

Novel application of pluronic lecithin organogels (PLOs) for local delivery of synergistic combination of docetaxel and cisplatin to improve therapeutic efficacy against ovarian cancer.

The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug delivery with a pluronic lecithin organogel (PLO) to facilitate high drug concentrations at tumor sites and less nonspecific distribution to normal organs is thought to be beneficial in chemotherapy. In this study, using Capryol-90 (C90) with the addition of lecithin as the oil phase was developed to carry DTX, which was then incorporated into a PLO-containing CIS to formulate a dual-drug injectable PLO for local delivery. An optimal PLO composite, PLO, composed of PF127:lecithin:C90 at a 13:0.

Quantitative contributions of processes by which polyanion drugs reduce intracellular bioavailability and transfection efficiency of cationic siRNA lipoplex.

RNA Interference (RNAi) is a potentially useful tool to correct the detrimental effects of faulty genes; several RNAi are undergoing clinical evaluation in various diseases. The present study identified the relative contributions of three mechanisms by which polyanion drugs reduced the gene silencing activity of Lipoplex, a complex of small interfering RNA (siRNA) and cationic liposomes. The study used a siRNA against the chemoresistance gene survivin and two model polyanion drugs (suramin, heparin).

Oil-in-water microemulsions stabilized by 3-(N,N- dimethylalkylammonio)propanesulfonate surfactants of varying alkyl chain length: Solubilisation of testos-terone propionate.

Solubilisation of the poorly-water soluble drug, testosterone propionate, in co-surfactant-free, dilutable, oil-in-water microemulsions stabilized by zwitterionic surfactants of varying alkyl chain length, namely 3-(N,N-dimethyloctylammonio)propanesulfonate and 3-(N,N-dimethyldodecylammonio)propanesulfonate and containing one of four ethyl ester oils, has been investigated. Both 3-(N,N-dimethyloctylammonio)propanesulfonate and 3-(N,N-dimethyldodecylammonio)propanesulfonate-stabilized microemulsions containing two short chain length oils, ethyl butyrate and ethyl caprylate, while only 3-(N,N-dimethyldodecylammonio)propanesulfonate formed microemulsions incorporating the longer chain length oils, ethyl palmitate and ethyl oleate, albeit to a very much reduced extent. Significantly the microemulsions containing the short chain length oils, ethyl butyrate and ethyl caprylate solubilised more testosterone propionate than the corresponding micelles.