Water-insoluble Drugs Research Articles

Layer-by-layer assembly of quercetin-loaded zein/γPGA/low-molecular-weight chitosan/fucoidan nanosystem for targeting inflamed blood vessels

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (−25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels.

Formulation and Evaluation of Natural Excipient-based Mucoadhesive Salbutamol Sulphate Tablets

When creating a mucoadhesive sustained-release formulation for oral consumption, aquaphilic matrices are a captivating option to consider. These aquaphilic matrices are used to release water-soluble and water-insoluble drugs. Gums and mucilages used in the current study are linseed mucilage (LM) and tamarind seed polysaccharide (TSP). The present work aims to focus on the possibilities of using these polysaccharides to prepare a new medication delivery system. The aim of the research was to make a salbutamol sulfate mucoadhesive tablet for the treatment of asthma. The wet granulation method was adopted for the formulation of the salbutamol sulfate mucosal adhesive tablet. Mucosal adhesive tablets were assessed for multiple parameters. The drug release is low as the amount of gums and mucilages is high. A mucoadhesive tablet containing linseed mucilage and chitosan exhibits good mucoadhesive performance and in-vitro drug release. Optimized formulation FM1 fits the Higuchi plot of release kinetics

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p < 0.01) after after two hours of the experiment than it had been (p < 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

Solubility Enhancement and Antioxidant Potential of Silymarin: A Poorly Water-soluble Drug

Background: Silymarin is extracted from the seeds of milk thistle (Silybum marianum), exhibits antioxidant properties, and is considered to treat numerous hepatic ailments like chronic liver disease, cirrhosis, and chemical degradation of liver cells and prevent hepatotoxicity from various drugs. Objective: The objective of the present study was to preclude the problem of poor dissolution of the relatively water-insoluble drug by formulating solid dispersions of the drug. Methods: Solid dispersions of silymarin were prepared by solvent evaporation method by using different polymers, i.e., PEG 6000 and poloxamer 407, in various ratios such as 1:2, 1:4 and 1:6. The compatibility of ingredients with the drug was tested by using Differential scanning calorimetry (DSC), X-Ray Diffractometry, and Fourier Transform-Infrared Spectroscopy (FT-IR). The scavenging activity of DPPH (2,2 diphenyl-1-picrylhydrazyl) radical was used to study the antioxidant activity, and an in vitro release study was conducted using phosphate buffer pH 6.8 as dissolution medium followed by the kinetic assessment to study the drug release mechanism. Results: Solid dispersions with different polymers were successfully prepared by the solvent evaporation method. FTIR spectroscopy and DSC showed no chemical interaction between the drug and polymers. Powder XRD analyses of optimized solid dispersions showed a relative decrease in crystallinity compared to the pure drug. The dissolution profile of solid dispersions successfully exhibited 90.78% drug released, and the optimized batch was found to follow Higuchi drug release kinetics with an R2 value of 0.990. Furthermore, the optimized formulation F6 showed higher antioxidant activity compared to pure silymarin and ascorbic acid. Conclusion: The elevated bioavailability, as well as absorption, consistently regulates the specific therapeutic effect of the water-insoluble drug. The specific response of silymarin to various bodily functions upgrades various activities like anti-aging effects, anti-cancer, antihypertensive, etc. Solid dispersion of drugs with good aqueous solubility results in a decrease in dose frequency and enhanced specificity of the drug mechanism.

SUSTAINABLE GREEN ANALYTICAL CHEMISTRY: SPECTROPHOTOMETRIC METHOD DEVELOPMENT OF DAPAGLIFLOZIN AND OMEPRAZOLE BY USING ECO-FRIENDLY SOLVENT

The present research’s aim was to develop analytical method utilizing ecologically suitable solvent which enhances solubility of analyte, sensitivity of the method etc. An analytical method was developed for the estimation of dapagliflozin (DGZ) and omeprazole (OPZ) by using aqueous 0.1 N HCl on the UV-VIS spectrophotometer. Wavelengths 223 nm and 282.5 nm were set to measure absorbance of DGZ and OPZ respectively. The results of different spectral characteristic techniques were examined to select the parameters and the design was validated against the ICH Q 2 R1 regulatory guidelines. The linearity of the drug was determined at a concentration of 1 to 50μg/ml and 1 to 32μg/ml for DGZ and OPZ respectively. The accuracy was found within acceptable limit with standard deviation 1.1874 to 6.4984 for DGZ and 0.1401 to 0.9843 for OPZ; and the assay study data was found 99.77 % for DGZ and 97.92 % for OPZ. The stability study of the method was performed out by minute variation in the wavelength, scan speed. The developed method is rigid, robust and efficient for the estimation of DGZ and OPZ from their respective dosage form. The effort was made to develop green or eco-friendly analytical method utilizing hydrotropic solvent for water insoluble drug dapagliflozin and omeprazole. KEYWORDS: Green method, Dapagliflozin, Omeprazole, analytical method, eco-friendly solvent, UV spectroscopy.

Lipid nanodiscs spontaneously formed by an amphiphilic polymethacrylate derivative as an efficient nanocarrier for molecular delivery to intact cells.

There is a great demand for the technology of molecular delivery into living cells using nanocarriers to realise molecular therapies such as gene delivery and drug delivery systems. Lipid-based nanocarriers offer several advantages for molecular delivery in biological systems, such as easy preparation, high encapsulation efficiency of water-insoluble drug molecules, and excellent biocompatibility. In this paper, we first report the interaction of lipid nanodiscs spontaneously formed by the complexation of an amphiphilic polymethacrylate derivative and phospholipid with intact cells. We evaluated the internalisation of polymethacrylate-based lipid nanodiscs by intact HeLa cells and applied them to the delivery of paclitaxel (PTX), an anticancer drug. The lipid nanodisc showed excellent uptake efficiency compared to conventional liposomes at a concentration where nanodiscs do not show cytotoxicity. In addition, the nanodisc encapsulating PTX showed significantly higher anticancer activity than PTX-loaded liposomes against HeLa cells, reflecting their excellent activity in delivering payloads to intact cells. This study demonstrated the potential of a polymethacrylate-based lipid nanodisc as a novel nanocarrier for molecular delivery to intact cells.

P-Sulfonatocalix[4]arene turns peptide aggregates into an efficient cell-penetrating peptide.

A novel cell-penetrating peptide (CPP) called FAM-Y4R4, with FAM as a fluorescent probe, was developed. Initially, we aimed to use Y4 as a supramolecular host for water-insoluble drugs, with R4 driving the complex into cells. However, an unexpected hurdle was discovered; the peptide self-assembled into amorphous aggregates, rendering it ineffective for our intended purpose. Molecular dynamics simulations revealed that intermolecular cation-π interactions between arginine and tyrosine caused this aggregation. By decorating the R4 sidechains with p-sulfonatocalix[4]arene (CX4), we successfully dissolved most of the aggregates, significantly improved the peptide's solubility and enhanced the cell uptake with MCF7 and A549 cells via both direct penetration and endocytosis. The binding strength between CX4 and R4, as well as the interaction between curcumin and tyrosines was quantified. Encouragingly, our results showed that FAM-Y4R4, with CX4, effectively delivered curcumin - as a model for poorly water-soluble drugs - into cells which exhibited potent anticancer activity. Using R4/CX4 instead of the conventional R7-9 oligoarginine-based CPP simplifies peptide synthesis and offers higher yields. CX4 shows promise for addressing aggregation issues in other peptides that undergo a similar aggregation mechanism.

Self-assembly of interpolyelectrolyte complexes and mixed micelles from guanidinium and phosphonate derivatives of p–tert–butylthiacalix[4]arene and solubilization of paclitaxel

In this work, supramolecular assemblies based on p–tert–butylthiacalix[4]arene derivatives functionalized with charged guanidinium and phosphonate fragments in the 1,3–alternate conformation were obtained in the presence of the surfactants. Two main approaches based on the macrocyclic compounds have been presented for supramolecular assembling, i.e. (i) the use of two oppositely charged macrocyclic compounds forming interpolyelectrolyte complexes; and (ii) the use of ionogenic macrocycles and low molecular surfactants forming mixed micelles. Self-assembling properties of guanidinium and phosphonate derivatives of p–tert–butylthiacalix[4]arene and paclitaxel solubilization of interpolyelectrolyte complexes and mixed micelles were examined and compared for various compositions. The obtained supramolecular associates were further investigated to load hydrophobic anticancer drug paclitaxel that is insoluble in water and requires solubilization prior to application. It was established that mixed micelles containing thiacalix[4]arene with guanidinium fragments were more effective in solubilizing paclitaxel against interpolyelectrolyte approach. The micelles obtained in the presence of water-insoluble drug formed stable monodisperse colloidal system consisted of spherical particles (d = 192 ± 7 nm, ζ = 33 ± 4 mV for equimolar ratio of the components). The results offer a new strategy for the design of the interpolyelectrolyte complexes based on the macrocyclic building blocks for the solubilization of water-insoluble drugs.

The Development of Lipid-Based Sorafenib Granules to Enhance the Oral Absorption of Sorafenib.

Sorafenib (SFN) is an anticancer multi-kinase inhibitor with great therapeutic potential. However, SFN has low aqueous solubility, which limits its oral absorption. Lipids and surfactants have the potential to improve the solubility of water-insoluble drugs. The aim of this study is thus to develop novel lipid-based SFN granules that can improve the oral absorption of SFN. SFN powder was coated with a stable binary lipid mixture and then absorbed on Aeroperl 300 to form dry SFN granules with 10% drug loading. SFN granules were stable at room temperature for at least three months. Compared to SFN powder, SFN granules significantly increased SFN release in simulated gastric fluid and simulated intestinal fluid with pancreatin. Pharmacokinetics and tissue distribution of SFN granules and SFN powder were measured following oral administration to Sprague Dawley rats. SFN granules significantly increased SFN absorption compared to SFN powder. Overall, the lipid-based SFN granules provide a promising approach to enhancing the oral absorption of SFN.

Nanocrystallization - A Tool for Enhancement of Solubility and Dissolution Rate for Water Insoluble Drugs

An innovative method to increase the solubility of water insoluble drug by using Nanocrystallization. Various factor like solubility, dissolution drug release, temperature, ph, have its effect on these process. Solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Solutes are classified as highly soluble, sparingly soluble, or insoluble based on the concentration. Dissolution is ability of molecule to get break down in it. There are seven different types of dissolution apparatus defined in the United States Pharmacopeia (USP)-basket type, paddle type, reciprocating cylinder, and flow through cell, paddle over disc, rotating cylinder, and reciprocating disc. Drug release is when drug solutes migrate from the initial position in the polymeric system to the polymer's outer surface and then to the release medium. It is directly related to the drug stability. There are many mechanisms by which the drug release can be controlled in a system: dissolution, diffusion, osmosis, partitioning, swelling, erosion, and targeting. Drug Stabilizers are compounds, usually polysaccharides, which are added to products to provide and preserve structure, stability, and viscosity. Broadly there are 3 methods for the nanocrystallizationi.e. Bottom up technique, Top down technique and combination technique.

Natural biomass-derived carbon dots as a potent solubilizer with high biocompatibility and enhanced antioxidant activity.

Numerous natural compounds exhibit low bioavailability due to suboptimal water solubility. The solubilization methods of the modern pharmaceutical industry in contemporary pharmaceutical research are restricted by low efficiency, sophisticated technological requirements, and latent adverse effects. There is a pressing need to elucidate and implement a novel solubilizer to ameliorate these challenges. This study identified natural biomass-derived carbon dots as a promising candidate. We report on natural fluorescent carbon dots derived from Aurantia Fructus Immatures (AFI-CDs), which have exhibited a remarkable solubilization effect, augmenting naringin (NA) solubility by a factor of 216.72. Subsequent analyses suggest that the solubilization mechanism is potentially contingent upon the oration of a nanostructured complex (NA-AFI-CDs) between AFI-CDs and NA, mediated by intermolecular non-covalent bonds. Concomitantly, the synthesized NA-AFI-CDs demonstrated high biocompatibility, exceptional stability, and dispersion. In addition, NA-AFI-CDs manifested superior free radical scavenging capacity. This research contributes foundational insights into the solubilization mechanism of naringin-utilizing AFI-CDs and proffers a novel strategy that circumvents the challenges associated with the low aqueous solubility of water-insoluble drugs in the field of modern pharmaceutical science.

Green Analytical UV-VIS Spectrophotometric Method Development of Valsartan by using Hydrotropic agent

The aim of the present research was to increase the solubility of valsartan in water by hydrotropic solubilisation. Hydrotopes are surface active, highly water soluble organic salt, which imparts solubility to insoluble or sparingly soluble organic compounds in water, which is when present at higher concentration. An analytical method was developed for the estimation of valsartan by UV-VIS spectrophotometry. Solvent 1% w/v sodium acetate solution was utilized and 247.2nm was the wavelength for measurement of absorbance. Effect of input variables on spectrum characteristics were studied for selection of critical parameters and developed method was validated as per ICH Q 2 R1 regulatory guidelines. Linearity of the drugs was ascertained over the conc range 4-48mcg/ml (microgram/ml). The accuracy was found within acceptable limit with nominal conc102.68 – 105.10 %; and the precision study was shown acceptable data as %SD varied from 1.88573 to 3.97617. The stability of the method was studied by minor variation in the wavelength, scan speed and acid, alkali and peroxide stress degradation study. The developed method is rigid, robust and efficient for the estimation of VST from the dosage form. The effort was made to develop green or eco-friendly analytical method utilising hydrotropic solvent for water insoluble drug valsartan.

Prediction of enhanced drug solubility related to clathrate compositions and operating conditions: Machine learning study

Although complexation technique has been documented as a promising strategy to enhance the dissolution rate and bioavailability of water-insoluble drugs, prediction of the enhanced drug solubility related to clathrate compositions and operating conditions is still a challenge. Herein, clathrate compositions (drug content (DC), drug molecular weight (M) and molar ratio (Ratio)), operating conditions (drug concentration (C), pH, pressure (P), temperature (T) and dissolution time (t)) under the different excipients (PEG, PVP, HPMC and cyclodextrin) as main solubilizers of the clathrates condition as input parameters were used to predict two indexes (drug dissolved percentage and dissolution efficiency) simultaneously through machine learning methodfor the first time. The results show that PVP as the main solubilizer of clathrates had higher prediction accuracy to the drug dissolved percentage, and HPMC as the main solubilizer of clathrates had higher prediction accuracy to the drug dissolution efficiency. In addition, the influence of various factors and interactions on the target variables were analyzed. This study affords achievable hints to the quantitative prediction of the drug solubility affected by various compositions and different operating conditions.

Oleogel-based drug delivery for the treatment of periodontitis: current strategies and future perspectives.

Periodontitis is the chronic inflammation of tooth-supporting tissues that leads to loss of tooth support if untreated. Conventional therapy for periodontitis (mechanical removal of microbial biofilm and oral hygiene enforcement) is augmented by anti-microbial and anti-inflammatory drugs. These drugs are frequently delivered locally into the periodontal pocket for maximum efficiency and minimum adverse effects. The potential of oleogels for periodontal drug delivery has been discussed and further, the future scope of oleogel-based drug delivery systems in dentistry. An oleogel-based local drug delivery system offers several advantages over other systems. Superior mechanical properties (firmness and compressibility), muco-adhesion, shear thinning, thixotropy, controlled drug release and the ability to incorporate water-insoluble drugs clearly distinguish and highlight the potential of oleogels as periodontal local drug delivery systems. Bigels can combine the qualities of both hydrogels and oleogels to provide a more promising option for drug delivery. However, there is limited evidence concerning oleogels as local drug delivery agents in periodontics. Further studies are needed to discern the clinical efficacy of oleogel-based drug delivery systems.

Formulation of multicomponent inclusion complex of cyclodextrin-amino acid with Chrysin: Physicochemical characterization, cell viability and apoptosis assessment in human primary glioblastoma cell line

Chrysin (CR) is a water-insoluble drug reported for different therapeutic effects. The microwave irradiation method was used in this study to create a multicomponent inclusion complex (CR-MC) containing CR (drug) and carrier hydroxyl propyl beta cyclodextrin (HP β CD) and L-arginine (LA). The prepared inclusion complex (CR-MC) was evaluated for dissolution study and results were compared with chrysin physical mixture (CR-PM). Further, the samples were assessed for infra-red (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM) and molecular docking. Finally, the cell viability, reactive oxygen species and flow cytometer studies were also assessed to check the potential of the prepared inclusion complex on the human primary glioblastoma cell line (U87-MG cell). The phase solubility findings revealed a stability constant (773 mol L−1) as well as a complexation efficiency of 0.027. The dissolution study displayed a significant increase in CR release from CR-MC (99.03 ± 0.39%) > CR-PM (70.58 ± 1.16%) > pure CR (35.29 ± 1.55%). NMR and IR spectral data revealed no interaction between CR and carriers. SEM and DSC study results revealed the conversion into amorphous form. The molecular docking results illustrated a high docking score, which supports the findings of complex formation. The cell viability, reactive oxygen species, and flow cytometry studies results showed enhanced activity from CR-MC against the tested human primary glioblastoma cell line. From the results it has been observed that chrysin solubility significantly increased after complexation and there in vitro activity also enhanced against cancer cell line.

Unforeseen consequences of synergizing PEGylated rapamycin and quercetin in angiogenesis and metastasis inhibition: Turning failure into benefit

Cancer continues to be a significant health hazard to the patient’s body around the globe, with more than 19 million incidents in 2020 worldwide, according to the world health organization, and it is expected to surpass 30 million in 2040. The advancement of nanomedicine focuses on enhancing the anticancer drugs that suffer from poor water solubility, unspecific cytotoxicity, and unfavorable pharmacokinetic properties. The most promising nanocarriers would be biodegradable and biocompatible, making the anticancer drugs soluble, preventing their aggregation, and enabling site-specific targeting. Herein, we formulated a rational design of two anticancer drugs (PEGylated rapamycin and quercetin) in a single micellar nanosystem, the ideal nanocarrier for water-insoluble drugs. After encapsulation, cytotoxicity and cellular uptake were increased. The quercetin loaded PEGylated rapamycin micelles (QRPM) exhibited significantly higher in vitro cytotoxicity in breast cancer cells than free drugs, mainly because of higher cellular uptake achieved via micelles. Moreover, the pharmacodynamic investigations indicated that QRPM significantly inhibited tumor growth compared to free drugs and PEGylated rapamycin micelles. Generally, QRPM could dramatically enhance the antitumor activity. They might be a promising drug delivery platform for anti-angiogenesis, -migration, and -invasion therapy as the nanosystem dramatically inhibited them compared with free drugs.

Dopamine-functionalized pectin-based Pickering emulsion as an oral drug delivery system

Pickering emulsions can be utilized to improve the usage efficiency of water-insoluble drugs as oral drug delivery systems. The present study showed a series of dopamine-functionalized pectin-based Pickering emulsions for anti-inflammatory medication. The dopamine functionalization induced significant differences in wettability, zeta potential, particle size, and PDI value compared with the oxidized pectin. The resultant Pickering emulsions consequently had excellent stability and could be stored for 30 days. Moreover, the morphology of the dried Pickering emulsions was all nano-scale spherical particles. Indomethacin (IND) was used as a water-insoluble drug model. The resultant Pickering emulsion-based drug delivery system showed persistent release of IND for more than 12 h, high pH-responsiveness, and biocompatibility. All the results manifested the excellent potential of dopamine-functionalized pectin-based Pickering emulsions in drug delivery applications. The present work also provided a new approach to preparing Pickering emulsions from modified anionic polysaccharides for delivering the water-insoluble drugs.

Bile Acid Salt as a Vehicle for Solubilization and Electrodeposition of Drugs and Functional Biomolecules for Surface Modification of Materials

This investigation addresses the need in biocompatible biosurfactants for electrophoretic deposition (EPD) of biomaterials. It is motivated by unique multifunctional properties of bile acid salts. Sodium cholate CHOLNa is a primary bile acid salt, which can solubilize and disperse different functional biomaterials. The EPD mechanism of pure EPD involves electrophoresis (EP) of CHOL− micelles, their discharge and gelation of cholic acid (CHOLH) to form anodic CHOLH films. The EPD strategy for immobilization of different functional biomolecules is based on the formation and EP of mixed micelles. Curcumin(CCM), hydrocortisone (HCS), and indomethacin (IDM) are used as model electrically neutral water insoluble drugs for EPD of composite films. CHOLNa acts as a solubilizing agent, which forms mixed micelles with the electrically neutral drugs for their EPD and formation of composite films. The pH-dependent charge of various functional biomolecules and charge reversal at isoelectric points prevents their deposition. This problem is addressed by the use CHOLH for co-deposition with bovine serum albumin (BSA) and hemoglobin (Hb), which are used as model proteins for EPD of CHOLH-BSA and CHOLH-Hb films. Another challenge is related to EPD of functional biomolecules with pH-independent charge, such as heparin (HP). The feasibility of deposition of CHOLH-HP films is demonstrated. The deposition mechanisms, film composition, and films morphologies are discussed. The approach developed in this investigation offers advantages of the use of biosurfactants as charging and gel-forming agents and mild EPD conditions for fabrication of films for drug delivery, biosensors, and surface modification of biomedical implants.

Zeolitic Imidazolate Framework-8 (ZIF-8) as a Drug Delivery Vehicle for the Transport and Release of Telomerase Inhibitor BIBR 1532.

Telomerase is constitutively overexpressed in the majority of human cancers and telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy. BIBR 1532 is a well-known synthetic telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of telomerase. However, water insolubility of BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive drug delivery vehicle for improved transport, release and anti-tumor effects of BIBR 1532. Herein, ZIF-8 and BIBR 1532@ZIF-8 were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of BIBR 1532 in ZIF-8 coupled with an improved stability of BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of BIBR 1532 with more accumulation in the nucleus. BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of cancer cells as compared with free BIBR 1532. A more potent inhibition on hTERT mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in BIBR 1532@ZIF-8-treated cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.

Pharmacokinetic studies of hyperoside-2-hydroxypropyl-β-cyclodextrin inclusion complex and ameliorated DSS-induced colitis in mice.

An inclusion complex formation with cyclodextrin is a promising method to improve the bioavailability of water-insoluble drugs. The pharmacokinetic characteristics of Hyperoside-2-hydroxypropyl-β-cyclodextrin inclusion complex in rats were evaluated. Compared with Hyperoside, the results showed that maximum plasma concentration and AUC0-t indexes of Hyperoside inclusion complex in rat plasma were increased, the value of half-life time was prolonged, and the value of apparent clearance was decreased, which proved that Hyperoside complexed with 2-hydroxypropyl-β-cyclodextrin could improve its bioavailability and increase its blood concentration. Secondly, the therapeutic effect of Hyperoside before and after complexing was further compared through the dextran sodium sulfate-induced colitis in mice. The experimental results showed that under the same dose, the Hyperoside inclusion complex had a better therapeutic effect, which could significantly increase the body weight of mice, improve the disease activity index, alleviate colon shortening, improve pathological colon changes, and have a better protective effect on colitis mice. According to 16S rDNA sequencing analyses, Hyperoside-2-hydroxypropyl-β-cyclodextrin may have an anti-inflammatory effect by increasing the abundance of beneficial bacteria (e.g. Firmicuria) and decreasing the proportion of harmful bacteria (e.g. Bacteroidetes) to balance the colon's microbiota.