Delivery Of Insoluble Drugs Research Articles

Local dermal delivery of cyclosporin A, a hydrophobic and high molecular weight drug, using dissolving microneedles

Dissolving microneedles (MN) containing cyclosporin A (CyA) were prepared for local delivery of CyA into the dermal layer. The efficacy of using MN to deliver CyA, an insoluble and high molecular weight drug, was observed and compared with oral administration of solubilized CyA.Microneedles containing CyA (CyA MN) were prepared using a closed, low-temperature molding process. The mechanical properties of CyA MN and phase separation were studied regarding the content of CyA. CyA MN were inserted into porcine skin for a predetermined time, and the dissolution and delivered amount of CyA were measured in vitro with an optical microscope and high-performance liquid chromatography (HPLC) analysis of the extracted CyA. A pharmacokinetic study of CyA MN was performed in vivo by administering 10% CyA MN, and the pharmacokinetic profile was compared with that of orally administered CyA.Pyramidal CyA MN (600 μm long, 250 μm wide) were prepared. CyA MN penetrated skin successfully with up to 50% CyA content. When 10% CyA MN were pressed into porcine skin for 60 min, 65% of MN length was dissolved and 34 ± 6.5 μg of CyA in MN was delivered into the skin. Under the same conditions with 10% CyA MN administered to rats, CyA MN showed Tmax of 8 h, Cmax of 15.9 ng/ml, and area under curve (AUC) of 686, compared to Tmax of 2 h, Cmax of 18.205 ng/ml, and AUC of 254 for oral administration of solubilized CyA.A therapeutic dose of CyA for treatment of psoriasis was delivered via MN into the skin layer without solubilization of CyA. Due to the hydrophobic properties and high molecular weight of CyA, the safety of CyA delivery was improved using dissolving microneedles because the slow systemic absorption and local treatment enabled CyA to remain in the skin for a longer time. Microneedles are an effective method with high bioavailability for local dermal delivery of insoluble drugs.

Hydrazone cross-linked micelles based on redox degradable block copolymer for enhanced stability and controlled drug release

In this work, an amphiphilic copolymer, PCL-SS-P(PEGMA-co-MAEBA), which contained a disulfide joint in backbone was designed and synthesized. The subsequent micelles that self-assembled from the copolymers were cross-linked by hydrazone, resulting in novel stimuli-responsive degradable micelles with a reversible cross-linked shell. By way of the hydrazone cross-linking of the micellar shell, SCMs owned a good stability against the extensive dilution by water or organic solvent. Doxorubicin (DOX) was used as the model drug for studying the in vitro release profiles of the SCMs. In normal physiological conditions at pH7.4, a quite slow speed was observed with DOX release (only 23% after 72h); when conditions were changed to pH5.0, the SCMs successfully de-crosslinked, DOX release was accelerated (62%). Moreover, drug release was further promoted and reached 87% when 10mM GSH was present, which was primarily due to the breakage of the disulfide joint. The intracellular uptake assay proved that DOX from DOX-loaded SCMs could be efficiently delivered into HepG2 cells after 12h incubation. MTT assays confirmed that DOX-loaded SCMs owned a high cytotoxicity against HepG2 cells. These redox-responsive, degradable SCMs could be a potential candidate for efficient insoluble anticancer drug delivery and therapy.

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol-dihydroartemisinin conjugate.

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol–dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG–DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs.

Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin

Novel catanionic lipid nanosystems (CLNs) incorporating curcumin (CCM) were developed, and improvements in pharmacokinetics and enhanced anti-lung cancer activity were observed. CCM was present in a lipid matrix surrounded by cationic, anionic and zwitterionic surfactants, forming the core-shell nanosystems. Compared with free CCM, the CCM-CLNs had much higher oral and intravenous bioavailabilities due to enhanced absorption and reduced clearance. The CCM-CLNs exhibited greater cytotoxicity in Lewis lung cancer (LLC) cells, which might have been due to increased antiproliferative, proapoptotic and anti-invasive activities and induction of cell cycle arrest. The CCM-CLNs increased the antitumor efficacy of CCM and decreased the tumor growth rate in tumor-bearing mice. This is the first report of induction of apoptosis in LLC cells by CCM through the PI3K/Akt/FoxO1/Bim signaling pathway. Catanionic lipid nanocarriers show promise for the therapeutic delivery of insoluble anti-tumor drugs.

Denatured globular protein and bile salt-coated nanoparticles for poorly water-soluble drugs: Penetration across the intestinal epithelial barrier into the circulation system and enhanced oral bioavailability

Oral drug delivery is the most preferred route for patients; however, the low solubility of drugs and the resultant poor absorption compromise the benefits of oral administration. On the other hand, for years, the overwhelmingly accepted mechanism for enhanced oral absorption using lipid nanocarriers was based on the process of lipid digestion and drug solubilization in the small intestine. Few reports indicated that other bypass pathways are involved in drug absorption in the gastrointestinal tract (GIT) for oral delivery of nanocarriers. Herein, we report a new nanoemulsion system with a denatured globular protein with a diameter of 30nm, soybean protein isolates (SPI), and bile salt as emulsifiers, aiming to enhance the absorption of insoluble drugs and explore other pathways for absorption. A BCS class II drug, fenofibrate (FB), was used as the model drug. The SPI and bile salt-coated Ns with a diameter of approximately 150nm were prepared via a high-pressure homogenizing procedure. Interestingly, the present Ns could be converted to solid dosage form using fluid-bed coating technology, maintaining a nanoscale size. Most importantly, in a model of in situ rat intestinal perfusion, Ns could penetrate across the intestinal epithelial barrier into the systemic circulation and then obtain biodistribution into other tissues. In addition, Ns significantly improved FB oral absorption, exhibited as a greater than 2- and 2.5-fold increase in Cmax and AUC0−t, respectively, compared to the suspension formulation. Overall, the present Ns are promising nanocarriers for the oral delivery of insoluble drugs, and the penetration of intact Ns across the GIT barrier into systemic circulation may be a new strategy for improved drug absorption with the use of nanocarriers.

Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen

A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10nm, 0.19±0.1, −12.4±0.1mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs.

Novel nanoparticles composed of chitosan and β-cyclodextrin derivatives as potential insoluble drug carrier

This research was aim to develop novel cyclodextrin/chitosan (CD/CS) nanocarriers for insoluble drug delivery through the mild ionic gelation method previously developed by our lab. A series of different β-cyclodextrin (β-CD) derivatives were incorporated into CS nanoparticles including hydroxypropyl-β-cyclodextrin (HP-β-CD), sulphobutylether-β-cyclodextrin (SB-β-CD), and 2,6-di-O-methy-β-cyclodextrin (DM-β-CD). Various process parameters for nanoparticle preparation and their effects on physicochemical properties of CD/CS nanoparticles were investigated, such as the type of CD derivatives, CD and CS concentrations, the mass ratio of CS to TPP (CS/TPP), and pH values. In the optimal condition, CD/CS nanoparticles were obtained in the size range of 215–276 nm and with the zeta potential from 30.22 mV to 35.79 mV. Moreover, the stability study showed that the incorporation of CD rendered the CD/CS nanocarriers more stable than CS nanoparticles in PBS buffer at pH 6.8. For their easy preparation and adjustable parameters in nanoparticle formation as well as the diversified hydrophobic core of CD derivatives, the novel CD/CS nanoparticles developed herein might represent an interesting and versatile drug delivery platform for a variety of poorly water-soluble drugs with different physicochemical properties.

An overview of recent patents on nanosuspension.

Pharmaceutical scientists involved in drug discovery and drug development are facing serious problems with newer poorly water soluble drugs with respect to their dissolution and bioavailability. Reducing the particle size of active pharmaceutical ingredient has been an efficient and reliable method for improving the bioavailability of insoluble drugs. Nanosuspension has emerged as an efficient and promising strategy for delivery of insoluble drugs due to its unique advantages such as ease of modification, process flexibility, targeting capabilities, altered pharmacokinetic profile leading to safety and efficacy. These unique features of nanosuspension have enabled its use in various dosage forms, including specialized delivery systems such as oral, parenteral, peroral, ocular and pulmonary routes. Currently, efforts are being directed to extend their applications in site-specific drug delivery. Large numbers of products based on nanosuspension are in the market and few are under clinical trials. The commercialization potential of nanosuspension based formulation for oral route is well established and products for other routes will enter the market within short span. Among the various techniques available, only wet milling technique has been successfully used for commercial production of nanosuspension. Nanosuspension based patents have extensive potential of reaching faster in the market as compared to other nanotechnology based formulations. This review covers various aspects of techniques of preparation, route of administration and commercialization of nanosuspension with main focus on the recent patents granted in the field.

Design of freeze-dried Soluplus/polyvinyl alcohol-based film for the oral delivery of an insoluble drug for the pediatric use

Spironolactone (SL) is a poorly water-soluble drug. Being poorly soluble affects its dissolution rate which in turn affects its oral bioavailability. This work aimed to prepare freeze-dried SL-Soluplus®/polyvinyl alcohol (PVA) oral thin film in an attempt to enhance the drug solubility on one hand and at the same time prepare a solid dosage form convenient for the pediatric use. SL-Soluplus®/PVA films were prepared using polyethylene glycol 400 (PEG 400) as a plasticizer applying the solvent-casting technique. The prepared films were evaluated for their thickness, tensile strength, and in vitro dissolution studies. Box–Behnken design (17 runs) was applied to optimize the effects of the formulation variables on the film properties. The optimized film formulation was freeze-dried after casting so as to enhance the drug dissolution. Moreover, the optimized freeze-dried film was re-characterized in vitro and evaluated in vivo in human volunteers to investigate its palatability and satisfaction. The results showed that the optimized formulation composed of 10% polymer concentration containing Soluplus®:PVA (0.33:0.66) and plasticized with 30% PEG 400 possessed the highest desirability value (0.836). Freeze-drying of the optimized formulation succeeded to improve SL in vitro dissolution due to the preparation of a more porous film compared to the non-freeze-dried one. In vivo evaluation of the optimized freeze-dried film showed high satisfaction among the participating volunteers concerning the ease of administration and sensation thereafter, where all the film specimens dissolved without the need for water and no film residues remained in the mouth following film dissolution. In conclusion, freeze-dried Soluplus®/PVA-based oral thin film proved to be a successful carrier for the oral delivery of insoluble drugs like SL for pediatrics.

ROS-induced biodegradable polythioketal nanoparticles for intracellular delivery of anti-cancer therapeutics

This study introduces biodegradable poly(1,4-phenyleneacetone dimethylene thioketal) (PPADT) nanoparticles as an intracellular delivery carrier for anti-cancer therapeutic applications. PPADT is synthesized through condensation polymerization of 2,2-dimethoxypropane and 1,4-benzenedimethanethiol. The synthesized PPADT is used to prepare polymeric nanoparticles encapsulated with Nile red or paclitaxel. The presence of reactive oxygen species (ROS) facilitates the polymer degradation via breakage of the thioketal bonds, resulting in disruption of the nanoparticle structure and release of the encapsulated molecules. Therapeutic effects of the paclitaxel-loaded PPADT nanoparticles are demonstrated using PC-3 prostate cancer cells, while no significant cytotoxic effects of placebo PPADT nanoparticles are observed. Our study suggests that ROS-sensitive biodegradable PPADT nanoparticles can be a new promising material for intracellular drug delivery of insoluble drugs.

Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded water-soluble amino acid-modified β-cyclodextrin platinum complexes

The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV–visible (UV–vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug.

Uniform iron oxide hollow spheres for high-performance delivery of insoluble anticancer drugs

As an intrinsic characteristic of many anticancer drugs, low solubility in physiological conditions limits the usage of these active ingredients in clinics. To overcome this bottleneck, we attempt to design and construct a high-performance magnetic-targeted delivery system based on uniform iron oxide hollow spheres. Via a facile one-pot solvothermal route, well-defined iron oxide hollow spheres were prepared with inexpensive inhesion. Compared with previously reported mesoporous Fe3O4 nanoparticles, our iron oxide hollow spheres have a larger void space giving the structures a higher storage capacity for guest molecules. In our present work, camptothecin (CPT) was selected as a model insoluble anticancer drug to confirm the efficiency of drug-loading and chemotherapy in vitro. Detailed anticancer efficacy was further investigated by using MTT assays and microscope imaging methods, indicating that these iron oxide hollow spheres are promising for insoluble drug delivery.

Nanostructure-based platforms-current prospective in ophthalmic drug delivery.

The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been attempted to increase the bioavailability and the duration of action of ocular drugs. This review provides an insight into various novel approaches; hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very recently in the delivery of insoluble drugs, prolonging the ocular residence time, minimize pre-corneal drug loss and, therefore, bioavailability and therapeutic efficacy of the drugs. Despite various scientific approaches, efficient ocular drug delivery remains a challenge for pharmaceutical scientists.

The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol

Objective: To explore the suitable application of MCM-41 (Mobil Composition of Matter number forty-one)-type and MCM-48-type mesoporous silica in the oral water insoluble drug delivery system.Methods: Cilostazol (CLT) as a model drug was loaded into synthesized MCM-48 (Mobil Composition of Matter number forty-eight) and commercial MCM-41 by three common methods. The obtained MCM-41, MCM-48 and CLT-loaded samples were characterized by means of nitrogen adsorption, thermogravimetric analysis, ultraviolet-visible spectrophotometry, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and powder X-ray diffractometer.Results: It was found that solvent evaporation method was preferred according to the drug loading efficiency and the maximum percent cumulative drug dissolution. MCM-48 with 3D cubic pore structure and MCM-41 with 2D long tubular structure are nearly spherical particles in 300–500 nm. Nevertheless, the silica carriers with similar large specific surface areas and concentrating pore size distributions (978.66 m2/g, 3.8 nm for MCM-41 and 1108.04 m2/g, 3.6 nm for MCM-48) exhibited different adsorption behaviors for CLT. The maximum percent cumulative drug release of the two CLT/silica solid dispersion (CLT-MCM-48 and CLT-MCM-41) was 63.41% and 85.78% within 60 min, respectively; while in the subsequent 12 h release experiment, almost 100% cumulative drug release were both obtained. In the pharmacokinetics aspect, the maximum plasma concentrations of CLT-MCM-48 reached 3.63 mg/L by 0.92 h. The AUC0–∞ values of the CLT-MCM-41 and CLT-MCM-48 were 1.14-fold and 1.73-fold, respectively, compared with the commercial preparation.Conclusion: Our findings suggest that MCM-41-type and MCM-48-type mesoporous silica have great promise as solid dispersion carriers for sustained and immediate release separately.

The Effect of N-Alkyl Substituents on the Usability of Imidazolium Cation-Based Ionic Liquids in Microemulsion Systems: A Technical Note

Ionic liquids (ILs) are predominantly hailed as green solvents, due to their non-volatile, recyclable and non-hazardous nature. Their wide-spectrum applications can be implemented into conventional fields like lubricants, battery electrolytes and synthetic reaction media as well as newer arenas including supramolecular chemistry, separation techniques, and nuclear fuel reprocessing (1–4). However, due to their tunable physicochemical properties, some recent reports have suggested novel pharmaceutical uses of ionic liquids, including their use as active pharmaceutical ingredient salts (5), antimicrobials (6), solubilizers (7), and drug delivery systems (8,9). ILs are known to enhance the solubility profile of poorly water-soluble drugs (7,10). Therefore, the use of IL-based drug carrier systems could be a rational approach for delivery of insoluble drugs. Microemulsions are thermodynamically stable, isotropic systems composed of a polar phase (usually water), a nonpolar phase (oils) and amphiphilic phase (surfactant or mixture of surfactants). These systems provide numerous advantages over conventional drug delivery vehicles including nanometer sized aggregations, long-term stability, biocompatibility, easy preparation, and high solubilization tendency (11). Nevertheless, drug delivery using microemulsions is yet to fully attain its true potential, considering that only type and content of oils and surfactants have been customized, in general, by formulators to achieve different desirable characteristics. Little efforts have been performed in the direction of modifying the polar phase of microemulsion systems. We attempted to use ILs as alternative polar dispersed phase (in place of water) in the microemulsion systems. Moniruzzaman et al., recently have prepared the IL-based microemulsion carrier for drug delivery of poorly hydrophilic drugs (12). The report describes the use of dimethylimidazolium dimethylphosphate for successful transdermal delivery of poorly soluble drugs. However, to the best of our knowledge, we are for the first time reporting the screening of room temperature ionic liquids from two different series of 1- and 3-alkyl substituted imidazolium bromides to be used as components of microemulsion vehicles. The current study explains the synthesis of some imidazolium cation-based ILs with varying carbon chain length. Also, preliminary in vivo toxicity of these compounds was assessed by hemolysis assay using human blood to establish the possibility of using the ILs safely, and investigating relationship between N-alkyl substituents and their toxicity. Further, their effect on the microemulsion phase behavior was studied by constructing their pseudoternary phase diagrams using isopropyl myristate (IPM) as oil phase and Span 80 and Tween 80 mixture as emulgent phase. Model microemulsion systems consisting of the above mentioned ingredients were prepared and characterized.

Targeted Delivery of Insoluble Cargo (Paclitaxel) by PEGylated Chitosan Nanoparticles Grafted with Arg-Gly-Asp (RGD)

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, we developed a tumor-targeting delivery system for insoluble drug (paclitaxel, PTX) by PEGylated O-carboxymethyl-chitosan (CMC) nanoparticles grafted with cyclic Arg-Gly-Asp (RGD) peptide. To improve the loading efficiency (LE), we combined O/W/O double emulsion method with temperature-programmed solidification technique and controlled PTX within the matrix network as in situ nanocrystallite form. Furthermore, these CMC nanoparticles were PEGylated, which could reduce recognition by the reticuloendothelial system (RES) and prolong the circulation time in blood. In addition, further graft of cyclic RGD peptide at the terminal of PEG chain endowed these nanoparticles with higher affinity to in vitro Lewis lung carcinoma (LLC) cells and in vivo tumor tissue. These outstanding properties enabled as-designed nanodevice to exhibit a greater tumor growth inhibition effect and much lower side effects over the commercial formulation Taxol.

Synthesis, Characterization and In Vitro Evaluation of Self-Assembled poly(ethylene glycol)-glycyrrhetinic Acid Conjugates

Glycyrrhetinic acid (GA) is a commonly used drug for the chemotherapy of Chronic Hepatitis B, allergic dermatitis, inflammation, etc. But some problems such as poor water-solubility, low bioavailability and short plasma halflife, have limited its use. In the present study, PEGylation derivatives of GA derivatives were synthesized and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, etc. The PEG-GA conjugates having a critical micelle concentration of 0.081-0.73 mg/mL were used to form nano-sized micelles, with mean diameters of 120.86 ± 31.74 nm. The physico-chemical properties of the PEG – GA conjugate were evaluated including stability, cellular toxicity, and drug release profile. All the conjugates synthesized showed good stabilities in acidic and neutral solutions, while the stability in alkaline solution and the enzymatic hydrolysis rate, were significantly affected by the linkage between the GA and PEG chain. The results demonstrate that, by PEGylation of GA derivatives, the greatly increased water solubility and desirable self-assembly abilities of PEG-GA were obtained. The novel conjugates have potential medical applications for intravenously delivery of insoluble drug delivery. Keywords: Glycyrrhetinic acid, in vitro evaluation, micelles, poly(etylene glycol), self assembly, antitumor activities, glycyrrhizic acid, drug delivery, nontoxic, biocompatible

Hybrid mesoporous gadolinium oxide nanorods: a platform for multimodal imaging and enhanced insoluble anticancer drug delivery with low systemic toxicity

We present a facile and scalable method to synthesize PEGylated Eu3+ doped mesoporous gadolinium oxide nanorods for multifunctional biomaterials. By incorporating a facile hydrothermal method, an in situ thermal decomposition process and a surface-modified procedure together, the resultant PEGylated Gd2O3:Eu nanorods reveal rod-like morphology, perfect photoluminescent/magnetic properties, as well as well-defined mesopores. Cell-cytotoxicity assays, hemolyticity against human red blood cells and post-injection histology analysis further demonstrate the excellent biocompatibility of the multifunctional nanorods, indicating the feasibility for their use in disease diagnosis and chemotherapy. The capability of nanorods as contrast agents for MR/X-ray/PL imaging is evaluated in detail through preliminary in vivo characterization. Moreover, to overcome the limitations of insoluble anticancer drugs in clinical applications, we further develop a simple but efficient method to prepare hydrophobic drug (Camptothecin) nanocrystallites in the inner voids of nanorods and testify their enhanced chemotherapy efficiency. Our findings indicate the enhanced chemotherapy efficiency of CPT nanocrystallite-loaded nanorods over traditional CPT-loaded nanoparticles. Due to these advantages, the well-designed PEGylated Gd2O3:Eu nanorods are promising for a simultaneous bioimaging and drug delivery system, which show further potential for clinical applications.

Iron Oxide Nanotubes for Magnetically Guided Delivery and pH‐Activated Release of Insoluble Anticancer Drugs

AbstractLow solubility in water is an intrinsic property of many drugs, which hinders the clinical use of those active ingredients. To break this bottleneck, we attempt to develop an iron oxide nanoparticle‐based multifunctional system. Firstly, we perform PEG coating and compare the feasibility of spherical and rod‐like iron oxide nanoparticles in a view of carcinoma cellular uptake; rod‐like nanoparticles attracted our interest since they could be quickly and massively internalized. For paclitaxel (PTX) loading, we next transform the nanorods into a tube structure by a hydrothermal method. The results show that drug crystals can be successfully loaded in the inner voids of these nanotubes (PMNTs) by controlling the crystallization process of PTX. The acquired nanocomplexes not only escape phagocytosis of macrophage cells by a PEG stealth effect, but also exhibit an increased cellular uptake with magnetic field exposure. In addition, this iron oxide‐based drug carrier possesses a low pH‐activated release profile, which would accelerate drug release in the carcinoma cells and minimize non‐specific drug release. Owing to these advantages, PMNTs promote the anticancer efficacy of PTX and clearly exhibit promising potential for using as high‐efficiency insoluble drug delivery system in clinical applications.

A novel nanomatrix system consisted of colloidal silica and pH-sensitive polymethylacrylate improves the oral bioavailability of fenofibrate

A novel solid particle system with a nanomatrix structure and without surfactant for the oral delivery of insoluble drugs was prepared. This used a combination of pH-sensitive polymethylacrylate and nano-porous silica, in order to improve the drug absorption using only pharmaceutical excipients and a relative simple process. The in vitro drug dissolution and in vivo oral bioavailability of this formulation, using fenofibrate as the model drug, were compared with other reference formulations such as a suspension, micronized formulation or self microemulsion drug delivery system (SMEDDS). The supersaturation stabilizing effect of different polymers was evaluated and the physicochemical characterization of the optimal formulation was conducted by SEM, TEM, surface area analysis, DSC, and XRD. The optimized formulation prepared with polymethylacrylate (Eudragit®L100-55) and silica (Sylysia®350) markedly improved the drug dissolution compared with other reference preparations and displayed a comparative oral bioavailability to the SMEDDS. Fenofibrate existed in a molecular or amorphous state in the nanomatrix, and this state was maintained for up to 1 year, without obvious changes in drug release and absorption. In conclusion, the nanomatrix formulation described here is a promising system to enhance the oral bioavailability of water-insoluble drugs.