Poor Water Soluble Drugs Research Articles

Formulation and Evaluation of Nano-particles Loaded with Salvia miltiorriza by Homogenization Method

Aims: The aim of the present study is to formulate and evaluate the Salvia miltorrhizaloaded Nano-structured lipid carriers(SM-NLC) in order to enhance the aqueous solubility and bioavailability as the efficacy of Salvia miltiorriza extract has been restricted due to less solubility and low bioavailability. Introduction: Salvia miltiorrhiza is a well-known Chinese herb that belongs to the family Labiatae. The herb has been widely used to treat various kinds of ailments, and its main phytochemical constituents are Tanshinone I, Tanshinone II, Miltirone, and Salvionolic acid, which are mainly found in the extract of roots. These Phytochemical constituents are responsible for several pharmacological activities such as anti-oxidant, anti-microbial, anti-hyperlipidemic, anti-inflammatory, cardiovascular diseases etc. Objective: Nano-lipid carriers are useful in enhancing the solubility of poor water-soluble drugs. The faulty lattice arrangement of Nano-lipid carriers (NLC) provides better entrapment, thus providing more space for the drug to incorporate in the lattice structure of NLC, improving the stability of the formulation and preventing the drug leakage from the matrix. Methods: SM-NLCs were prepared by using oleic acid and stearic acid as liquid and solid lipids, respectively and tween 80 as the surfactant by high-speed homogenization method. The optimization of SM- NLC was performed by applying the Box-Behnken experimental design. The independent variables were chosen as the amount of lipids, surfactant concentration, and sonication time, whereas dependent variables were opted as particle size and entrapment efficiency. The influence of different proportions of the lipids (Stearic acid and Oleic acid) and the surfactant (Tween 80) was analysed on the dependent variables. The optimized formulation was evaluated for Particle size (241.7nm±3), Polydispersity index (.249 ±0.05), Zeta Potential (-14.6±5), and entrapment efficiency (82.49%). Scanning Electron Microscopy (SEM) was performed to identify the surface morphology, and the entrapment of the drug into the nanostructured matrix was verified by Differential Scanning Calorimetry. The interaction between the formulations was confirmed by performing FTIR. The dialysis bag method was performed to calculate the in vitro drug release from the optimized formulation. Additionally, a stability study was performed for 1 month of duration. Result: The SM NLCs were successfully formulated based on the Box-Behnken design. Particle size, PDI, zeta potential, and EE demonstrated less than a 5% difference compared to the predicted value. The formulations did not show any possible interactions with the lipids. The optimized formulations were found stable after one month of stability studies. Conclusion: The above results confirmed that Salvia miltiorrhiza could be effectively formulated in the form of a nanostructured-lipid carrier system. The formulation and evaluation of nanoparticles have been performed successfully using the homogenization method.

Amino-functionalised mesoporous silica nanoparticles for the delivery of isoniazid and its metal complexes

The effective delivery of poor water-soluble anti-tubercular drugs such as isoniazid to their target sites is a major factor that has made it difficult for tuberculosis to be eradicated. Isoniazid derivatives and nano-particulate drug delivery systems are explored as one way to address this limitation. This study investigated the use of amino-functionalised mesoporous silica nanoparticles (MCM-41) as nano-carriers for the delivery of isoniazid-based metal complexes, Cu–INH and Fe–INH. The Sol-gel method was used to synthesise the nano-carriers, which produced a series of well-ordered nano-carriers. Their physicochemical properties were modified through surface functionalisation with amino groups via post-grafting synthesis. The isoniazid-based metal complexes were incorporated into the nano-carriers using rotary evaporation. The nano-carriers were characterised using X-ray diffraction (XRD), Zeta potential, Fourier Transmission Infra-red (FT-IR), Brunaeur Emmett Teller (BET), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Thermogravimetric analysis (TGA). These characterisation techniques confirmed the successful surface functionalisation of the nano-carriers with amino groups and their encapsulation with INH, Cu–INH and Fe–INH. The amino-functionalised nano-carriers were observed to have the highest drug loading capacities and entrapment efficiencies within the range of 7.85%–19.31 % and 39.26%–96.53 %, respectively. The release rates of INH, Cu–INH, and Fe–INH from the nano-carriers were also studied in Phosphate Buffer Solution (PBS) with pH of 7.4 and 5.4 using ultraviolet–visible spectroscopy. The cumulative release rates of INH, Cu–INH, and Fe–INH from their nano-carriers depended on their release media's textural properties and environmental conditions. Amino functionalised nano-carriers had high release rates, with A-MCM-41+Cu–INH having the highest of 37.09 % in PBS at 5.4 after 24 h. The cumulative data obtained was fitted into Zero order, First order, Hixson Crowell, Higuchi, Korsmeyer-Peppas and Weibull models. The Hixson Crowell, Korsmeyer-Peppas, and Weibull models fitted well with correlation coefficients (R2) of 0.9813, 0.9769 and 0.9802, respectively, for MCM-41+INH in PBS of pH 5.4.

Improving the Solubility and Bioavailability of Progesterone Cocrystals with Selected Carboxylic Acids.

Progesterone (PROG) is a natural steroid hormone with low solubility and high permeability that belongs to biopharmaceutics classification system class II. In this study, novel pharmaceutical cocrystals of PROG were successfully prepared by solvent evaporation or a liquid-assisted grinding process aimed at enhancing its solubility and bioavailability. The cocrystal formers selected based on crystal engineering principles were carboxylic acids, namely, 4-formylbenzeneboronic acid (BBA), isophthalic acid (IPA), and 3-nitrophthalic acid (NPA). The cocrystal structures were characterized using multiple techniques. Single-crystal X-ray diffraction results showed that the carbonyl group, acting as a hydrogen bond acceptor, was pivotal in the cocrystal network formation, with C-H···O interactions further stabilizing the crystals. The cocrystals exhibited improved solubility and dissolution profiles in vitro, with no significant changes in hygroscopicity. The parallel artificial membrane permeability assay (PAMPA) models indicated that the cocrystals retained PROG's high permeability. Pharmacokinetic studies in Sprague-Dawley rats revealed that all cocrystals increased PROG exposure, with AUC(0~∞) values for PROG-BBA, PROG-IPA, and PROG-NPA being 742.59, 1201.72 and 442.67 h·ng·mL-1, respectively. These values are substantially higher compared to free PROG, which had an AUC(0~∞) of 301.48 h·ng·mL-1. Notably, PROG-IPA provided the highest AUC improvement, indicating a significant enhancement in bioavailability. Collectively, the study concludes that the cocrystal approach is a valuable strategy for optimizing the physicochemical properties and oral bioavailability of PROG, with potential implications for the development of other poor water-soluble drugs.

Preparation of Ketoconazole-loaded Nanoemulsions for Ophthalmic Delivery: Characterization and In-vitro Antifungal Activity Evaluation

Background: Nanoemulsions (N.E.s) capable of ocular bioavailability elevation can be used for poor water-soluble drugs such as ketoconazole (K.Z.). The current investigation was designed for the purpose of overcoming this issue by developing K.Z. containing N.E.s for ophthalmic drug delivery with appropriate therapeutic efficiency. Methods: The preparation of ketoconazole N.E.s was performed by the low-energy technique. According to the phase diagram, three stable formulations were selected for more physicochemical analyses, including particle size, polydispersity index, pH, refractive index and viscosity. Finally, drug release patterns and in-vitro antifungal activity were assessed for the final selected formulation. Results: The developed N.E. formulations with droplet sizes less than 20 nm showed appropriate physicochemical characteristics for ocular delivery. The selected formulation released 100% of the encapsulated drug during 24 h. Moreover, antifungal assessments showed that prepared N.E. had acceptable in-vitro antifungal activity. Conclusions: Based on our findings, it can be concluded that N.E.s could be applied as effective carriers for the ophthalmic delivery of ketoconazole.

Formulation and characterization of glipizide solid dosage form with enhanced solubility.

Glipizide, a poor water-soluble drug belongs to BCS class II. The proposed work aimed to enhance the solubility of glipizide by preparing solid dispersions, using polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). Solvent evaporation method was used for the preparation of glipizide solid dispersions. Solid dispersions were prepared in four different drug-to-polymer ratios i.e. 1:1, 1:2, 1:3 and 1:4. Mainly effect of three polymers (PVP K30, PVP K90 and PEG 6000) was evaluated on the solubility and dissolution of glipizide. The in-vitro dissolution of all prepared formulations was performed under pH 6.8 at 37°C using USP type II apparatus. In-vitro dissolution results revealed that the formulations having high concentrations of the polymer showed enhanced solubility. Enhancements in the solubility and rate of dissolution of the drug were noted in solid dispersion formulations compared to the physical blends and pure drug. Solid dispersions containing polyvinyl pyrrolidone exhibited a more favorable pattern of drug release compared to the corresponding solid dispersions with PEG. An increase in the maximum solubility of the drug within the solid dispersion systems was observed in all instances. Two solid dispersion formulations were optimized and formulated into immediate-release tablets, which passed all the pharmacopoeial and non-pharmacopoeial tests. Fourier transformed Infrared (FTIR) spectroscopy X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) were used to indicate drug: polymer interactions in solid state. Analysis of the solid dispersion samples through characterization tests indicated the compatibility between the drug and the polymer.

An innovative carrier for the formulation of amorphous solid dispersion by hot-melt extrusion with no further downstream processes: a case study with indomethacin.

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding.

Electrospherization of genistein@DNA core-shell nanospheres as a drug delivery system and theoretical study of the release mechanism

Encapsulation of poor water-soluble drug was considered as one of the widely used approaches to overcome such obstacle. The goal of this research was in situ encapsulate the hydrophobic genistein (GEN) during the electrospherization (Es) of deoxyribonucleic acid (DNA) nanospheres as a delivery system with appropriate drug release properties. The prepared nanospheres (free GEN sample; Es DNA and GEN loaded DNA; Es GEN@DNA) were characterized using uv–visible spectroscopy (UV–vis), transmission electron microscope (TEM), zeta potential, Fourier transform infrared spectroscopy (FTIR), x-ray diffraction analysis (XRD), and stability test. In addition, the drug encapsulation % was studied, the drug release efficiency was recorded and theoretically visualized to understand the mechanism and kinetics of GEN drug release. The results revealed that GEN was successfully encapsulated during the DNA electrospherization as a core (GEN)/shell (DNA) like structure with a wonderful stability against time. The UV–vis patterns and their deconvolutions introduced that the emerged peak around 372–500 nm of Es GEN@DNA nanospheres has an area under curve larger than that of the free GEN sample. Zeta potential value decreased from −17.4 to −14.3 mV. In addition, TEM images confirmed the formation of a core/shell structure with average size 109.2 nm. XRD pattern of Es GEN@DNA revealed that GEN lost its crystalline phase, which indicated the incorporation of the drug. On the other hand, %Encapsulation of GEN within DNA nanospheres was found to be 89.62%. Es GEN@DNA release profile explored that the well entrapped GEN within the DNA nanospheres could be a promising for sustained drug release. Besides, the dilemma of using a fractal or fractional kinetics model was overcame by introducing a general fractional kinetic equation that involves a time-dependent rate coefficient, which introduced that the solution of the fractional kinetic model can fit the release data profiles.

Enhancement of bioavailability of herbal drugs for treating viral therapy using SNEDDS as the delivery system

SNEDDS were developed with the objective of treating low bioavailability of drugs for antiviral drugs due to its low solubility. The scientist has increased their interest in improving bioavailability and absorption of poorly-water soluble drugs using Self-Emulsifying lipid technology. SNEDDS was an isocratic mixture contains an Oil, Surfactant, Co-surfactant, and Drug in accurate amount. The SNEDDS was primarily prepared as liquid-SNEDDS, but S-SNEDDS was more stable as compared to L-SNEDDS. As viral infection was major threat for people due to its limited efficacy and Serious adverse effects. The most damaging viral diseases was treated with help of SNEDDS as delivery system. They were a leading cause of morbidity and mortality. The plant and plant source were major source from which the extracted metabolites used for synthesis of drug through metabolic pathway. The phytochemicals and extracts were better and safe alternative for synthetic drugs. The phytochemicals like Curcumin, Myricetin, Apigenin etc. used as drug for treating antivirals using SNEDDS. This technique was used for quantitative and qualitative analysis. Also, the ternary phase diagram gives dramatic representation of Oil, surfactant and Co-surfactant which shows its concentration. Some characterization techniques were Droplet size, Zeta potential, XRD, DSC, FTIR, and TGA. Also, QbD provides a platform for systemic production of drug formulations. QbD was used for its better bioavailability.

A novel solid formulation of rivaroxaban eutectic using a hot melt extruder with improved thermal stability and dissolution profile

The current work aims to enhance the solubility, dissolution rate and stability of the poor water-soluble drug rivaroxaban (RXB) by preparing the amorphous solid dispersion (ASD) of its eutectic with...

Model Informed-Development of Amorphous Systems (MI-DAS) - an in-silico polymer selection tool for ASD development

Forming amorphous solid dispersions (ASDs) is one method for improving the solubility and subsequent absorption of poorly-water soluble drugs. An ASD is a matrix of a poorly water-soluble compound with a hydrophilic polymer carrier, which stabilises the drug in its amorphous form. The choice of polymer is often made based on previous success and precedence in other ASD products, and not on the suitability for the drug in development. A bespoke in-silico polymer selection tool (PST) has been developed which selects polymers based on their structural complementarity with the drug. Here, we demonstrate how use of the PST in early development of the Tacrolimus ASD would have identified a more optimal polymer with better API miscibility.

Comprehensive Characterization and In vitro Evaluation of a Novel POQCL Drug Delivery System

Aim: Formulation and evaluation of the POQCL drug delivery system. Background: One of the major barriers in the formulation of dosage forms is the poor solubility of the drug. BCS class IV drugs are having a problem with pharmacokinetics or reaching the site of action. Poor water-soluble drugs of BCS class IV obstruct drug bioavailability and decrease their pharmaceutical development. An attempt has been made in this work to deliver the BCS class IV drug into a novel carrier dosage form i.e., liposomes using a novel lipid. Objective: Formulation of the POQCL drug delivery system. Characterization by average particle size, surface morphological analysis, % drug entrapment, drug loading, in vitro study of drug release, and kinetic models of drug release of the prepared POQCL formulation. Methods: POQCL was prepared by emulsification-evaporation technique with some modifications and evaluation was done by average particle size, surface morphological analysis, drug entrapment percentage, drug loading, in vitro study of drug release, and kinetic models of drug release. Results: The average size of particle and surface morphology of prepared POQCL were found to be 76.89 nm and spherical in shape. The percentage yield was found to be 62.5% for the POQCL formulation. The percentages of drug entrapment efficiency and loading capacity were found to be 90% and 47.36% respectively. The drug in vitro release outcomes were 24.27% within the 2 hours and 75.18% within 12 hours and followed the zero-order drug release kinetic model for the POQCL formulation. Conclusion: In this research study, we found that pilu oil is a useful novel lipid source in the formulation of liposome drug delivery for the encapsulation of BCS class IV drugs. POQCL formulation showed optimum average particle size with enhanced entrapment efficiency and drug loading as well as a sustained release of drug was found. In the future, the prepared liposomes of pilu oil may be considered as the choice of drug delivery system for BCS class IV drugs.

Solubility Enhancement of Lansoprazole by using Solid Dispersion Technique

In the existing study focused on the solubility enhancement of lansoprazole by using solid dispersion technique. Lansoprazole is proton pump inhibitor (PPI). Lansoprazole is used for the treatment of gastric ulcer. Lansoprazole is the Class II Drug of Biopharmaceutical Classification system. By using novel solid dispersion methods to enhance the oral solubility of poor water-soluble drug. Lansoprazole has the low solubility and high permeability. Hence to enhance the solubility of lansoprazole we prepared the Lansoprazole solid dispersion (SD) with PVP K30, Poly Ethylene Glycol 6000 (PEG 6000) and Poloxamer 407. Lansoprazoledissolving tablet were formulated using various superdisintegrants like Crospovidone and Sodium Starch Glycolate by Direct compression. The prepared the tablet is evaluated at various parameters like weight variation, hardness, friability, disintegration time, drug content uniformity and In-vitro dissolution. The In-vitro Drug release study of solid dispersions SD6 show the high drug release around 98.93%. Overall, in the all formulations F12 which contains 6%, 3.75% and 10% of Crospovidone, SSG and MCC release the 98.93% drug is the best formulation.

Formic acid-aided sample preparation method for sensitive and simultaneous analysis of eight nitrosamines in poorly-water soluble pharmaceutical drugs using liquid chromatography–ultraviolet detection

There has been a growing concern over the contamination of pharmaceutical products with nitrosamines (NAs) such as N-nitrosodimethylamine (NDMA). To quantify NA levels in drugs using reversed-phase liquid chromatography (LC), the sample solution should achieve a high drug concentration to detect trace NAs, and an appropriate amount of hydrophilic NAs should be retained. However, these are difficult to achieve, and no suitable method has yet been developed. The present study was the first to develop a sample preparation method to achieve this by combining drugs with formic acid (FA), followed by the removal of active pharmaceutical ingredients (APIs) from samples via crystallization. This method was successfully applied for the sensitive quantification of eight NAs in poorly water-soluble acidic atorvastatin (ATS) and basic itraconazole (ITC) via LC–ultraviolet (LC-UV) detection. The removal rate of ITC via recrystallization exceeded 99.96 %, whereas most NAs remained as solutes. Assuming that the enhancement in ITC solubility directly translates to heightened analytical sensitivity, a > 100-fold increase in sensitivity was attained compared to conventional methodologies. This sample preparation method would be applicable to other poorly water-soluble drugs, contributing to the control of NA content in various formulations to realize the safe delivery of pharmaceuticals to patients.

Preparation and Characterization of Carvedilol Solid Dispersion by Kneading Method

Solid dispersion using hydrophilic carrier is one of the approaches that has a potential to increase solubility, dissolution rate and consequently the oral bioavailability of poorly-water soluble drugs. In this study, class II drug "Carvedilol" (CVD) was used because of its poor solubility, it serves as a model drug that contributes to irregular dissolution and limited bioavailability. CVD: PVP K30 solid dispersion formulations SD1, SD2 and SD3 were prepared by kneading method at different weight ratios ,1:1; 1:2 and 1:4 respectively and evaluated for drug content, solubility and dissolution rate. Kneading method enhances the stability of drugs and suitable for processing thermolabile substances. The optimum solid dispersion ratio was characterized also for drug-carrier interaction by FTIR spectroscopy, and crystallinity by SEM and PXRD and compared with physical mixture and pure drug powder.
 The results showed that the solubility of carvedilol increased by increasing the proportion of PVP K30 used in the dispersion of the drug. On the other hand, dissolution study revealed a significant enhancement in the dissolution rate of the drug using solid dispersion compared to pure drug and physical mixture. X-ray diffraction of the solid dispersion suggest that the drug's transformation from crystalline to amorphous form may be responsible for the observed improvement in dissolving rate. The carvedilol solid dispersion improved the solubility and dissolution, which depend on the carrier concentration ratio. The dissolution of drugs increased with an increase in carrier content. The studies of PXRD, SEM, and FTIR revealed the amorphous nature of the drug in solid dispersion. The solid dispersion by kneading approach using PVP K30 as a carrier is a potential method for improving CVD's solubility and dissolution rate.

The effect of polymeric binder type and concentration on flow and dissolution properties of SMEDDS loaded mesoporous silica-based granules

Self-microemulsifying drug delivery systems (SMEDDS) are lipid-based formulations, designed to improve the solubility of poorly-water soluble drugs. Mesoporous silica is frequently used for SMEDDS solidification by various techniques. One of them is wet granulation, which enables achieving both high SMEDDS load and good flow properties. This study investigated the effect of six polymeric binders’ addition to granulation dispersion (GD) (povidone K30, povidone K90, copovidone, Pharmacoat® 603, Pharmacoat® 615 and Methocel™ K100 Premium LV) on characteristics of produced SMEDDS granules, prepared by wet granulation. By incorporation of polymer in GD, it was possible to produce mesoporous silica-based free-flowing granules, with preserved self-microemulsifying properties, responsible for improved in vitro release of carvedilol. The incorporation of higher molecular weight binders resulted in slower in vitro release, while high binder concentration was related to faster drug release. The highest release rate was achieved with povidone K30 at 7.45 % binder concentration, as corresponding granules exhibited complete drug release already in 5 min. Granulation method (manual vs. high-shear) influenced the release rate of carvedilol as it was released slower from SMEDDS granules prepared using the granulator.Finally, SMEDDS tablet formulation was optimized to achieve maximum granule content and adequate tablet hardness. Increased granule content found to negatively influence tablet hardness, as maximum granule content of 25 % was needed to obtain appropriate hardness. Such tablets exhibited short disintegration time, so this final prototype can be considered as orodispersible tablet.

Formulation and evaluation of topical piroxicam microemulgel for arthritis

Background: Piroxicam is an anti-inflammatory, analgesic, and antipyretic drug. Piroxicam is widely used in the management of chronic pain. The objective of this work was to develop and analyze topical Piroxicam microemulgel to improve drug solubility, enhance permeation, reduce GIT side effects reduce the frequency of the drug. Method: The Piroxicam microemulgel was prepared by drawing the pseudo ternary phase picture and water titration procedure. Formulation was prepared by using isopropyl myristate as an oil, Tween 80 as an surfactant, n-butanol as Co-surfactant and water. It was converted to gel by using 1% Carbopol 940 and few drops of ethanolamine. The prepared formulation was characterized for thermodynamic stability, pH, droplet size, viscosity, FTIR,DSC, electrical conductivity, dye solubility drug content, and in-vitro release using a Franz diffusion cell. Result: Microemulgel formulation was thermodynamically stable on visual inspection after being treated with a freeze-thaw cycle and centrifugation. pH of formulation was 6.5. The mean droplet size for ME gel was 100±0.472nm. The viscosity of the microemulgel was 90.4±0.01 cps which showed Newtonian flow. FTIR and DSC studies showed that microemulgel was compatible with its excipients. Electrical conductivity and dye solubility testing confirmed that the microemulgel was O/W. Piroxicam microemulsion gel showed 89.89% drug content and the release rate of piroxicam was 98±8.63% after 48h. It followed the Korsmeyer Pappas model which means it was a hydrogel-based system. Conclusion: Microemulsion gel formulation obtained remarkably inflated skin retention for piroxicam over the piroxicam gel. It might act as a promising vehicle for the topical delivery of poor water-soluble drugs.

Formulation and evaluation of topical piroxicam microemulgel for arthritis

Background: Piroxicam is an anti-inflammatory, analgesic, and antipyretic drug. Piroxicam is widely used in the management of chronic pain. The objective of this work was to develop and analyze topical Piroxicam microemulgel to improve drug solubility, enhance permeation, reduce GIT side effects reduce the frequency of the drug. Method: The Piroxicam microemulgel was prepared by drawing the pseudo ternary phase picture and water titration procedure. Formulation was prepared by using isopropyl myristate as an oil, Tween 80 as an surfactant, n-butanol as Co-surfactant and water. It was converted to gel by using 1% Carbopol 940 and few drops of ethanolamine. The prepared formulation was characterized for thermodynamic stability, pH, droplet size, viscosity, FTIR,DSC, electrical conductivity, dye solubility drug content, and in-vitro release using a Franz diffusion cell. Result: Microemulgel formulation was thermodynamically stable on visual inspection after being treated with a freeze-thaw cycle and centrifugation. pH of formulation was 6.5. The mean droplet size for ME gel was 100±0.472nm. The viscosity of the microemulgel was 90.4±0.01 cps which showed Newtonian flow. FTIR and DSC studies showed that microemulgel was compatible with its excipients. Electrical conductivity and dye solubility testing confirmed that the microemulgel was O/W. Piroxicam microemulsion gel showed 89.89% drug content and the release rate of piroxicam was 98±8.63% after 48h. It followed the Korsmeyer Pappas model which means it was a hydrogel-based system. Conclusion: Microemulsion gel formulation obtained remarkably inflated skin retention for piroxicam over the piroxicam gel. It might act as a promising vehicle for the topical delivery of poor water-soluble drugs.

Heparin - Pluronic F127 nanogel with optimal component ratio for drug delivery applications

This study aimed to synthesize a nanogel system based copolymers of Heparin (Hep) and Pluronic F127 (F127) with optimal Hep:F127 ratio for delivering poor water soluble drug and Platinum-based drugss. Firstly, Hep-F127 conjugates were formed via disulfide bridges of cystamine molecules. The obtained Hep-F127 systems were then proved and characterized using Proton nuclear magnetic resonance (1H-NMR), Dynamic Light Scattering (DLS)) methods. Cisplatin (CPT) was used as the Pt drug model, meanwhile Paclitaxel (PTX) was used as poor water-soluble drug model. The encapsulation ability for CPT and PTX was investigated and compared to choose the optimal Hep-F127 ratio. This Hep-F127 nanogel system is expected to be a good carrier for delivering drugs with different properties.

GPP-TSAIII nanocomposite hydrogel-based photothermal ablation facilitates melanoma therapy

ABSTRACT Background Photothermal therapy (PTT) is a promising cancer treatment, but its application is limited by low photoconversion efficiency. In this study, we aimed to develop a novel graphene oxide (GO)-based nanocomposite hydrogel to improve the bioavailability of timosaponin AIII (TSAIII) while maximizing PTT efficacy and enhancing the antitumor effect. Methods GO was modified via physical cross-linking with polyvinyl alcohol. The pore structure of the gel was adjusted by repeated freeze-thawing and the addition of polyethylene glycol 2000 to obtain a nanocomposite hydrogel (GPP). The GPP loaded with TSAIII constituted a GPP-TSAIII drug delivery system, and its efficacy was evaluated by in vitro cytotoxicity, apoptosis, migration, and uptake analyses, and in vivo antitumor studies. Results The encapsulation rate of GPP-TSAIII was 66.36 ± 3.97%, with slower in vitro release and higher tumor cell uptake (6.4-fold) compared to TSAIII. GPP-TSAIII in combination with PTT showed better bioavailability and antitumor effects in vivo than did TSAIII, with a 1.9-fold higher tumor suppression rate than the TSAIII group. Conclusions GPP is a potential vehicle for delivery of TSAIII-like poor water-soluble anticancer drugs. The innovative PTT co-delivery system may serve as a safe and effective melanoma treatment platform for further anticancer translational purposes.

Enhancing the oral bioavailability of poorly water-soluble amisupiride with solid nanodispersion

The limited oral bioavailability remains an essential challenge of poorly water-soluble amisupride (AMS). Herein, we designed a solid nanodispersion system of AMS (AMS-SN) by dispersing AMS into a polymeric matrix composed of Solutol HS-15, polyvinylpolypyrrolidone (PVPP), and poly (maleic anhydride-alt-1-octadecene) (PMHC18) to improve the oral bioavailability of AMS. AMS existed in the AMS-SN system in amorphous or molecular state. Moreover, AMS-SN could transform into nanometer-sized particles upon their exposure in the gastrointestinal fluids. Compared to the AMS suspension, the absorption of AMS in the duodenum, jejunum and ileum increased significantly by 8.02, 32.18 and 9.11-fold by the AMS-SN formulation, respectively. Particularly, the AMS-SN system produced an 8.58-fold enhancement of oral bioavailability of AMS. Therefore, solid nanodispersion provides a feasible pharmaceutical platform for oral delivery of poorly water-soluble drugs (PWSDs).