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Fucoidan is well known to have various biological functions and is often investigated for pharmaceutical applications. Several studies have been conducted on clinical applications of fucoidan in recent years, especially regarding its oral drug delivery. Although fucoidan has shown promising results in various dosage forms, its potential applications as a dietary supplement have been demonstrated, and recent studies show that oral administration of fucoidan is preferred. However, the focus on the oral delivery of fucoidan in recent studies has caused its potency in therapy to be understudied. This review aims to provide results on the promising fucoidan activity by oral administration with in vivo studies. In addition to using it as an active ingredient, the utilization of fucoidan as an excipient in oral drug delivery systems will be discussed. An overview of fucoidan administration by oral delivery in recent promising studies will provide a direction for further investigations in clinical applications, particularly for fucoidan, which has a broad spectrum of bioactive properties., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The freeze-drying process has been particularly attractive for preparing tablets for controlled drug release. Although traditional methods, such as granulation or direct compression methods, have been used in various studies to produce tablets with controlled release, freeze-drying processes have been utilized in certain circumstances due to their distinct advantages. However, overall, further development of these strategies, which started with early studies on orally disintegrating tablets, is still necessary. In this review, the incorporation of different formulations into freeze-dried tablets will be discussed. Moreover, the use of excipients, freeze-drying conditions, formulation reconstitution and tablet structure for optimizing the performance of freeze-dried tablets will be reported, including strategies with nanoformulations and natural materials. Generally, this discussion with potential approaches will benefit further development of freeze-dried tablets containing drugs in the pharmaceutical industry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Extracellular vesicles have an excellent ability to transfer their contents to cells. Extracellular vesicles can also be engineered to deliver therapeutic molecules to target cells. Although a number of studies have exploited synthesized nanoparticles in the treatment of neurological disease in the past few years, extracellular vesicles have been investigated and shown tremendous promise for clinical applications because they are safe and have strong targeting specificity. Different types of extracellular vesicles have been studied and modified for delivering therapeutic factors in neurological disease, including extracellular vesicles loaded with natural therapeutic factors and therapeutic molecules. In this review, we discuss delivery systems using extracellular vesicles containing molecules of interest and then focus on main strategies used for EV loading and surface modification. Discussing these important issues will support and facilitate the design and development of promising techniques and products for neurological therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The long history of discovery and recently encouraging studies of the anti-cancer effect of aspirin promise a closer step to widely used aspirin-based medication in cancer therapy. To resolve the poor water-solubility of aspirin and low encapsulation efficiency of exosomes for further developing a new delivery of aspirin as anti-cancer treatment, our nanoamorphous exosomal delivery platform was established. In this study, the anti-tumour effects of nanoamorphous aspirin-loaded exosomes with exosomes derived from breast and colorectal cancer cells, were comprehensively studied using both in vitro and in vivo models. These exosomes displayed enhanced cellular uptake via both clathrin-dependent and -independent endocytosis pathways, and significantly improved cytotoxicity of aspirin to breast and colorectal cancer cells, accompanied by the enhanced apoptosis and autophagy. Remarkably, this nanoamorphous exosomal platform endowed aspirin with the unprecedented cancer stem cell eradication capacity. Further animal study demonstrated that this developed exosomal system was able to efficiently deliver aspirin to in vivo tumours. The active targeting of these exosomes to tumour was further improved by conjugating an aptamer specifically targeting EpCAM protein. Hence, this nanoamorphous structured exosome system effectively transformed aspirin into a potential cancer stem cell killer with distinguished properties for clinical translation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite their great potential, the nano-sized extracellular vesicles are yet to become effective delivery systems for poorly water-soluble drugs. Here, we present a novel platform of exosomes as a drug delivery system by engineering of a poorly water-soluble drug into a poloxamer-based molecular nanostructured dispersion composed of a hydrophilic and a hydrophobic moiety for an enhanced anticancer efficacy. For the first time, aspirin was loaded into exosomes as an anticancer agent via a one-step fabrication combining the nano-matrix formation of the nanostructured dispersion and exosomes loading. Our approach could transform crystalline aspirin to a nanoamorphous form in the nano-matrix structured exosomes, leading to increased drug encapsulation efficiency for exosomes, improved dissolution and strongly enhanced cytotoxicity of aspirin to cancer cells. Interestingly, cytotoxicity of aspirin to both breast and colorectal cancer cells could be strongly enhanced by the nanoamorphous aspirin-loaded exosomes, and this cytotoxic effect was more pronounced to parental cells of the exosomes, reminiscent of homing effect. Hence, this study has pioneered a novel nanoplatform of nanoamorphous exosomal delivery system to transform an anti-inflammatory drug into a potent anti-cancer agent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The combination of gene therapy and chemotherapy has recently received considerable attention for cancer treatment. However, low transfection efficiency and poor endosomal escape of genes from nanocarriers strongly limit the success of the clinical use of small interfering RNA (siRNA). In this study, a novel pH-responsive, surface-modified single-walled carbon nanotube (SWCNT) was designed for the codelivery of doxorubicin (DOX) and survivin siRNA. Polyethylenimine (PEI) was covalently conjugated with betaine, and the resulting PEI-betaine (PB) was further synthesized with the oxidized SWCNT to form SWCNT-PB (SPB), which exhibits an excellent pH-responsive lysosomal escape of siRNA. SPB was modified with the targeting and penetrating peptide BR2 (SPBB), thereby achieving considerably higher uptake of siRNA than SWCNT-PEI (SP) or SPB. Furthermore, SPBB-siRNA presented substantially lower survivin expression and higher apoptotic index than Lipofectamine 2000. DOX and survivin siRNA were adsorbed onto SPB to form DOX-SPBB-siRNA, and siRNA/DOX was released into the cytoplasm and nuclei of adenocarcinomic human alveolar basal epithelial (A549) cells without lysosomal retention. Compared with SPBB-siRNA or DOX-SPBB treatment alone, DOX-SPBB-siRNA significantly reduced tumor volume in A549 cell-bearing nude mice, demonstrating the synergistic effects of DOX and survivin siRNA. Pathological analysis also indicated the potential therapeutic effects of DOX-SPBB-siRNA on tumors without distinct damages to normal tissues. In conclusion, the novel functionalized SWCNT loaded with DOX and survivin siRNA was successfully synthesized, and the nanocomplex exhibited effective antitumor effects both in vitro and in vivo, thereby providing an alternative strategy for the codelivery of antitumor drugs and genes.

The concept of click chemistry (CC), first introduced by K.B. Sharpless, has been widely adopted for use in drug discovery, novel drug delivery systems (DDS), polymer chemistry, and material sciences. In this review, we outline novel aspects of CC related to drug discovery and drug delivery, with a brief overview of molecular mechanisms underlying each click reaction commonly used by researchers, and the main patents that paved the way for further diverse medicinal applications. We also describe recent progress in drug discovery and polymeric and carbon material-based drug delivery for potential pharmaceutical applications and advancements based on the CC approach, and discuss some intrinsic limitations of this popular conjugation reaction. The use of CC is likely to significantly advance drug discovery and bioconjugation development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pharmaceutical dosage forms address diverse key components but satisfying unmet patient needs to enhance patient adherence is a major challenge. The desired design of patient-centered drug products should be based on characteristics of various components, such as patients, disease, routes of administration, drug delivery technologies and active pharmaceutical ingredients. Understanding of targeting patients and their physiological and biological environments is pivotal for developing suitable patient-centered drug products. In this review, key components of an ideal drug delivery system were considered. Then, stepwise approaches for designing patient-centered drug products were suggested. Finally, various case studies are also presented and considered to develop models of patient-centered drug products.

This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The objective of this study was to develop a novel solid self-nanoemulsifying drug delivery system (SNEDDS) using a membrane emulsification technique involving Shirasu porous glass (SPG) which produced very small and uniform emulsion droplets, resulting in enhanced solubility, dissolution and oral bioavailability of poorly water-soluble cilostazol. The effects of carriers on the drug solubility were assessed, and pseudo-ternary phase diagrams were plotted. Among the liquid SNEDDS formulations tested, the liquid SNEDDS composed of peceol (oil), Tween 20 (surfactant) and Labrasol (cosurfactant) at a weight ratio of 15/55/30, produced the smallest emulsion droplet size. The cilostazol-loaded liquid SNEDDS formulation was suspended in the distilled water and subjected to SPG membrane emulsification. Calcium silicate was added as a solid carrier in this liquid SNEDDS, completely suspended and spray-dried, leading to the production of a cilostazol-loaded solid SNEDDS. The emulsion droplet size, solubility and dissolution of the emulsified solid SNEDDS were assessed as compared to the solid SNEDDS prepared without emulsification. Moreover, the physicochemical characteristics and pharmacokinetics in rats were evaluated with the emulsified solid SNEDDS. The emulsified solid SNEDDS provided significantly smaller and more uniform nanoemulsions than did the non-emulsified solid SNEDDS. The emulsified solid SNEDDS showed significantly higher drug solubility and dissolution as compared to the non-emulsified solid SNEDDS. The crystalline drug in it was converted into the amorphous state. Moreover, in rats, it gave significantly higher initial plasma concentrations and AUC compared to the drug powder, suggesting its improved oral bioavailability of cilostazol. Thus, this novel solid SNEDDS developed using a membrane emulsification technique represents a potentially powerful oral delivery system for cilostazol., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The present study aimed to evaluate the gastrointestinal mucosa irritation of three platycodin formulations. Platycodin-loaded core pellets were prepared via extrusion-spheronization method and coated with Eudragit(®) L100-55 (L100) or Eudragit(®) S100 (S100) for pH-dependent release. The release of platycodin D from coated pellets exhibited pH dependent release profiles. The pharmacokinetic study in rats showed that Tmax of the coated pellets were prolonged as compared to that of un-coated pellets. The S100-coated pellets possess a lower Cmax and decreased AUC0-24h as compared to the L100-coated and uncoated pellets. Hematoxylin-eosin staining and nuclear factor Kappa B (NF-κB) measurement were carried out to observe the gastrointestinal mucosa irritations. The results revealed that the irritations of platycodin on the upper gastrointestinal mucosa are dose-dependent. However, no obvious irritation effect on the gastrointestinal tissues of rats was detected after oral administration of the coated pellets. In addition, the amount of NF-κB in the stomach of rats treated with the uncoated pellets was about fivefold higher as compared to that of the coated pellets. In summary, the L100-coated platycodin pellets exhibited higher oral bioavailability and less gastrointestinal mucosa irritations as compared to the other two formulations.

The intention of this study was to compare the physicochemical properties, stability and bioavailability of a clopidogrel napadisilate (CN)-loaded solid dispersion (SD) and solid self-microemulsifying drug delivery system (solid SMEDDS). SD was prepared by a surface attached method using different ratios of Cremophor RH60 (surfactant) and HPMC (polymer), optimized based on their drug solubility. Liquid SMEDDS was composed of oil (peceol), a surfactant (Cremophor RH60) and a co-surfactant (Transcutol HP). A pseudo-ternary phase diagram was constructed to identify the emulsifying domain, and the optimized liquid SMEDDS was spray dried with an inert solid carrier (silicon dioxide), producing the solid SMEDDS. The physicochemical properties, solubility, dissolution, stability and pharmacokinetics were assessed and compared to clopidogrel napadisilate (CN) and bisulfate (CB) powders. In solid SMEDDS, liquid SMEDDS was absorbed or coated inside the pores of silicon dioxide. In SD, hydrophilic polymer and surfactants were adhered onto drug surface. The drug was in crystalline and molecularly dispersed form in SD and solid SMEDDS, respectively. Solid SMEDDS and SD greatly increased the solubility of CN but gave lower drug solubility compared to CB powder. These preparations significantly improved the dissolution of CN, but the latter more increased than the former. Stability under accelerated condition showed that they were more stable compared to CB powder, and SD was more stable than solid SMEDDS. They significantly increased the oral bioavailability of CN powder. Furthermore, SD showed significantly improved oral bioavailability compared to solid SMEDDS and CB powder. Thus, SD with excellent stability and bioavailability is recommended as an alternative for the clopidogrel-based oral formulation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Many new drugs have been discovered in pharmaceutical industry and exposed their surprised potential therapeutic effects. Unfortunately, these drugs possess low absorption and bioavailability since their solubility limitation in water. Solid dispersion (SD) is the current technique gaining so many attractions from scientists due to its effect on improving solubility and dissolution rate of poorly water-soluble drugs. A number of patents including the most recent inventions have been undertaken in this review to address various respects of this strategy in solubilization of poorly watersoluble drugs including type of carriers, preparation methods and view of technologies used to detect SD properties and mechanisms with the aim to accomplish a SD not only effective on enhanced bioavailability but also overcome difficulties associated with stability and production. Future prospects are as well discussed with an only hope that many developments and researches in this field will be successfully reached and contributed to commercial use for treatment as much as possible.

In this work, a novel, biocompatible conjugates of gelatin and oleic acid (GOC) were synthesized by a novel aqueous solvent-based method that overcame challenges of completely contrary solubility between gelatin and oleic acid (OA). The GO nanoparticles (GONs) and Paclitaxel encapsulated nanoparticles (PTX-GON) were prepared by self-assembly in water. These nanoparticles (NPs) were then conjugated with folic acid (FA) for targeting cervical cancer cells (Hela cells) and were characterized for their various physicochemical and pharmaceutical properties. Fourier transform infrared spectroscopy (FT-IR) and 1H NMR studies indicated the successful synthesis of GOC which showed low critical aggregation concentration in water (0.015 mg/ml). All NPs were stable in human blood serum and their mean diameters were below 300 nm suitable for passive targeting. Powder X-ray diffraction (PXRD) diffractograms showed the reduction in drug crystallinity and hence, leading to the solubility enhancement of PTX. The release of PTX from both PTX-GON and FA conjugated PTX-GON (PTX-FA-GON) was controlled for a long time. The cytotoxicity results demonstrated great advantages of PTX-FA-GON and PTX-GON over the conventional dosage form of pacliaxel (Taxol). These results, therefore, indicate that GOC is a promising material to prepare drug encapsulated NP as a controlled delivery system and PTX-FA-GON is a potential targeted delivery system for cancer therapy.

The aim of this study was to develop novel mucoadhesive pellets containing valsartan (VAL) with enhanced oral bioavailability. Two types of VAL loaded core pellets were prepared by an extrusion/spheronization method, and further dry-coated with a mixture of hydroxypropylmethylcellulose (HPMC) and carbomer (CB) at different ratios. The effects of the pellet core composition, HPMC:CB ratio and coating level on the drug release from the coated pellets were investigated. The physicochemical properties of the core and coated pellets were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). In addition, the in vitro and in vivo mucoadhesion properties as well as the bioavailability of the coated pellets in rats were evaluated by using VAL suspension and core pellets as control preparations. The results of the release study demonstrated that the two types of core pellets, especially the pellets formulated with a solubilizer and a pH modulator gave considerably faster drug release than the VAL powder. However, the core and coated pellets exhibited similar release profiles indicating that the dry powder-coating did not retard the drug release. Strong molecular interactions were observed between the drug and the carriers in FT-IR analysis. The coated pellets displayed distinct mucoadhesive property in vitro and delayed gastrointestinal (GI) transit in vivo. Furthermore, the coated pellets exhibit significantly higher AUC(0-12h) and C(max), as compared to the core pellets and drug suspension. It was concluded that the mucoadhesive pellets could render poorly water soluble drugs like VAL with a rapid drug release, delayed GI transit and enhanced oral bioavailability., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Circadian rhythms regulate most body functions and are important factors to consider when administering drugs. The existence of circadian rhythms in nature and their influences on human biological systems have given rise to the concept of chronotherapy, which is the science of delivering drugs in a synchronized manner with the rhythm-dependent circadian variation inherent in the human body. The safety and efficacy of a drug can be improved by matching the peak plasma concentration during a 24 h period of the rhythms. An on-off pulsed (pulsatile or time-controlled) release drug-delivery system offers rapid and transient release; stepwise release; and the sustained release of a certain amount of drug within a short time period after a predetermined off-release period according to the circadian rhythm of disease states. These systems deliver the drug at the right time and at an appropriate dosage and are the best approach for chronotherapy. These systems show promise for the optimal therapy of chronic diseases such as asthma, hypertension, myocardial infarction and arthritis, which show a circadian dependency. Various technologies have been adopted to mimic circadian rhythms in physiological functions and diseases. This review focuses on the basic concept of circadian rhythm, chronotherapy and recent advances in the development of on-off pulsed oral drug-delivery systems for optimal therapy.

The 40th annual international conference of the Korean Society of Pharmaceutical Sciences and Technology on Pharmaceutical Technology, Biopharmaceutics and Drug Delivery was held on 2-3 December 2010 in Jeju Special Self-Governing Providence, Korea, to celebrate its 40th anniversary. A comprehensive review of a wide spectrum of recent topics on pharmaceutical technology, biopharmaceutics and drug delivery was presented. Invited lectures and poster presentations over 2 days were divided into six parallel sessions covering areas such as biotechnology, biopharmaceutics, drug delivery, formulation/manufacture, regulatory science and frontier science. Among these, there were two sessions related to regulatory science and biopharmaceutics that were co-sponsored by the Korea Food and Drug Administration. In fact, this conference provided an opportunity for many investigators to discuss their research, collect new information and to promote the advancement of knowledge in each pharmaceutical area. This conference report summarizes the keynote podium presentations provided by many distinguished speakers, including Gordon L Amidon of the University of Michigan.

The main objective of this study was to prepare a solid form of lipid-based self-emulsifying drug delivery system (SEDDS) by spray drying liquid SEDDS with an inert solid carrier Aerosil 200 to improve the oral bioavailability of poorly water-soluble drug dexibuprofen. The liquid SEDDS was a system that consisted of dexibuprofen, Labrasol, Capryol 90 and Labrafil M 1944 CS. The particle size analysis revealed no difference in the z-average particle diameter of the reconstituted emulsion between liquid and solid SEDDS. The solid SEDDS was characterized by SEM, DSC and XRD studies. In vivo results of solid SEDDS and dexibuprofen powder in rats at the dose of 10mg/kg showed that the initial plasma concentrations of drug in solid SEDDS were significantly higher than those of dexibuprofen powder (P<0.05). The solid SEDDS gave significantly higher AUC and Cmax than did dexibuprofen powder (P<0.05). In particular, the AUC of solid SEDDS was about twofold higher than that of dexibuprofen powder. Our results suggested that this solid SEDDS could be used as an effective oral solid dosage form to improve the bioavailability of poorly water-soluble drug dexibuprofen.

Enhanced delivery of bifidobacteria and fecal changes were compared following multiple oral administrations of protected bifidobacteria-loaded alginate poly-l-lysine microparticles (bap-microparticles) and unprotected bifidobacteria cultures over a period of 1 month to healthy human volunteers as preliminary in vivo studies. When bap-microparticles were orally administered, enhanced delivery of bifidobacteria was achieved. The viability of the bifidobacteria was significantly increased approximately 11.5-30 times (1.06-1.48 log cycles) during the ingestion period when compared with the bifidobacteria culture group (p < 0.05). However, other gut microflora such as bifidobacteria, enterobacteriaceae, lactic acid bacteria, and staphylococci in feces were not significantly different between the two groups. Encapsulated bifidobacteria resulted in more frequent defecation and decreased fecal viscosity.

[Display omitted] Industrial-scale pharmaceutical applications still face many challenges in overcoming the low absorption and bioavailability of poorly water-soluble drugs. Hot-melt extrusion has emerged as a promising approach with continuous processing on an industrial scale for the preparation of drug delivery systems. Many reviews have mentioned the potential applications, processes, principles and advantages and disadvantages of hot-melt extrusion in the pharmaceutical industry. However, a focus on the recent progress of hot-melt extrusion, which investigates the impacts of processes and formulations of solid dispersions of poorly water-soluble drugs, is missing. In this review, various factors, including polymers, drug properties, additives and surfactants, in solid dispersion SD formulations by hot-melt extrusion will be discussed. Moreover, the effects of the hot-melt extrusion process on the physicochemical properties of solid dispersions will be mentioned. The utilization of molecular interactions in hot-melt extrusion to improve drug stability will also be described. Overall, this summary of recent studies on solid dispersion by hot-melt extrusion will provide perspectives and effectiveness for the development of formulations containing poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

Background: Drug release from a solid form of self-emulsifying drug delivery system (SEDDS) has greatly been limited due to strong adsorption and physical interaction with carriers. To facilitate drug release process in the stomach, an acid-soluble powderizing carrier, Fujicalin® was evaluated together with different disintegrants and hydrophilic lubricants. Method: Immediate-release self-emulsifying tablets (IR-SETs) of ibuprofen (IBU) was prepared with solidified SEDDS of IBU, various disintegrants, and lubricants, and drug release was evaluated to develop IR-SET that can release IBU with a similar IBU release rate to that obtained with liquid SEDDS. Results: The liquid SEDDS consisted of Capryol 90, Cremophor EL, Labrasol, and IBU at a ratio of 3:4:3:3, and was solidified with various adsorbents. The powderized SEDDS was tabletted by a direct compression. Fujicalin®-based SEDDS tablets demonstrated remarkably higher dissolution rate of IBU compared with Neusilin® and Neosyl®-based SEDDS tablets. The IR-SET formula of IBU prepared with Fujicalin® as an adsorbent, Polyplasdone® as a disintegrant, and sodium bicarbonate as a co-disintegrant showed over 90% of initially loaded dose of IBU released within 5 min in a stimulated gastric juice (pH 1.2), exhibiting almost equivalent rate of IBU release to that shown by liquid SEDDS. The particle size analysis revealed no significant differences in droplet sizes of the microemulsions formed from liquid (116 nm) and IR-SET (110 nm). Conclusion: The novel IR-SET can be promising as a fast-releasing SEDDS tablet of IBU for fast onset of action. [ABSTRACT FROM AUTHOR]

Abstract: To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q10 (CoQ10), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ10 was formulated. The solubility of CoQ10 was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ10 was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and 10% (v/v) Capryol 90 of each excipient showed minimum mean droplet size (about 240nm) and optimal drug release profile in water. The pharmacokinetic study in rats for the optimized formulation was performed and compared to powder formulation. SEDDS have significantly increased the C max and area under the curve (AUC) of CoQ10 compared to powder (P <0.05). Thus, this self-micro emulsifying drug delivery system should be an effective oral dosage form for improving oral bioavailability of lipophilic drug, CoQ10. [Copyright &y& Elsevier]

Abstract: Recently, we synthesized novel amphiphilic gelatin–oleic acid (GO) conjugate to prepare self-assembled nanoparticles for drug delivery. The aim of this study was to investigate pharmaceutical potentialities of self-assembled GO nanoparticles for solubility enhancement and modified release of poorly water-soluble drugs. Three poorly water-soluble model drugs with different pH-dependent solubility (valsartan and aceclofenac, insoluble at pH 1.2; telmisartan, insoluble at pH 6.8) were chosen to investigate the potential contributions of self-assembled GO nanoparticles to solubility enhancement and controlled release. The particle size of the drug-loaded nanoparticles was 200–250nm. Zeta potential was calculated, and instrumental analysis such as powder X-ray diffraction (PXRD) and Fourier transform infrared (FT-IR) spectroscopy were used to investigate the physicochemical properties of the drug-loaded nanoparticles. Compared to the drug alone, the drug-loaded nanoparticles showed enhanced solubility. Furthermore, the release profiles of the model drugs were modified in a controlled manner. The current self-assembled GO nanoparticles can provide a versatile potential in drug delivery and tumor targeting. [Copyright &y& Elsevier]

Abstract: The present study aimed to develop the intranasal delivery system of fexofenadine for the prolonged drug release via the preparation of mucoadhesive liposome. By using thin layer film hydration method, liposome of fexofenadine was prepared with DPPC/DPPG, resulting in the small lipid vesicles (359±5.5 nm) with narrow size distribution (PI<0.1). Subsequently, the surface of anionic liposome was coated by chitosan and in vitro characteristics of liposomes were evaluated along with the pharmacokinetic studies in rats. Chitosan coated liposomes were stable for 6-month storage at 4°C without any significant size change and drug leakage. Furthermore, it exhibited strong mucoadhesive properties in mucin adsorption test, which was 3-fold higher than uncoated liposomes. Compared to the oral delivery of powder formulation, the intranasal delivery of fexofenadine significantly (p <0.05) increased systemic exposure of fexofenadine in rats. Particularly, the intranasal administration of chitosan coated liposome exhibited approximately 5 fold enhancement of AUC with more sustained drug release in rats compared to the oral delivery. In conclusion, intranasal administration of chitosan coated liposome appeared to be effective to enhance the bioavailability as well as prolonged exposure of fexofenadine in rats. [Copyright &y& Elsevier]

A major hurdle in cancer treatment is the precise targeting of drugs to the cancer site. As many cancer cells overexpress the transferrin receptor (TfR), the transferrin (Tf)-TfR interaction is widely exploited to target cancer cells. In this study, novel amphiphilic apo-Tf stearic acid (TfS) conjugates were prepared and characterized by Fourier transform infrared (FTIR) spectroscopy, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and trinitrobenzenesulfonic acid (TNBS) assay. The prepared TfS conjugates were readily self-assembled in water to form nanoparticles (NPs), consisting of TfS as a core of NPs, whose sizes and zeta potentials were determined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and a particle size analyzer. Hydrophilic water-soluble doxorubicin (DOX) was chosen as a model drug. DOX-loaded TfS NPs (NP + DOX), prepared by the adsorption of DOX on the NP surface via the incubation method, were analyzed for their cell targeting and killing efficiencies in TfR-overexpressing A549 and HCT116 cell lines by MTT assay, confocal microscopy, and fluorescence assisted cell sorting (flow cytometry). The data showed that NP + DOX exhibited improved cancer cell targeting and killing properties compared to that reported for free DOX. Further, the cytotoxic efficiency of NP + DOX was comparable to that of PEGylated liposomal product, Doxil ® , while its cellular uptake was higher than that of Doxil ® . Thus, this novel receptor-based TfS NP drug delivery system has great potential to target TfR-overexpressing cancer cells without off-target effects. [ABSTRACT FROM AUTHOR]

A new conceptual nanoparticle consisting of a silica-coated iron oxide magnetic core and a fattigation-based biocompatible shell with oleic acid and hydrophilic protein (gelatin). The prepared particle can be a useful theranostics platform material for diagnostic imaging and as a drug delivery system. Oleic acid and gelatin were conjugated on the silica-coated magnetic nanoparticle surface to provide three primary functionalities: 1) enhancing biocompatibility and solubility in aqueous solution and providing the ability to incorporate hydrophobic chemical drugs into the shell for delivery, 2) improving treatment-response magnetic monitoring as a diagnostic agent with low nanotoxicity, and 3) increasing anticancer efficacy owing to the controlled release of the incorporated drug in cells and in an animal model. We prepared magnetic-silica nanoparticles with super-paramagnetic properties, which are utilized as a T 2 -weighted magnetic resonance imaging agent. After formation of an oleic acid-gelatin shell, the prepared materials exhibited high loading capacity for a hydrophobic anticancer drug (paclitaxel). Our particle platform system exhibited higher therapeutic efficacy and lower toxicological effects in vitro and in an in vivo cancer model than a clinically available chemo-drug (Taxol®). Our findings strongly suggest that this nanoparticle system can serve as a platform for cancer therapy by the incorporation of chemical drugs. [ABSTRACT FROM AUTHOR]

Abstract: Superparamagnetic iron oxide (SPIO) nanoparticles have been intensively investigated as MRI probes due to the noninvasive detection of in vivo pathological changes. In the study, a nanosized system for SPIO delivery to a tumor was prepared to overcome the common challenges of SPIO nanoparticles such as insufficient uptake of SPIO by specific cells due to instability, short half-life by macrophage, and low efficiency of internalization. SPIO with ca. 6nm sizes as a MRI probe and PLA–PEG (5K–2K) as a biocompatible stable system were prepared. The hydrophobic modified SPIO were loaded into the core of micelles and showed a stable dispersion with 140–170nm particle sizes. The SPIO loading micelles showed higher relaxivity coefficients and increases of T 2 relaxation in vivo MR imaging. This SPIO delivery system with high stability and sensitivity can be a promising imaging formulation as MRI T 2 probes for tumor detection. [Copyright &y& Elsevier]

Abstract: In order to compare the effects of hydrophilic and hydrophobic solid carrier on the formation of solid self-microemulsifying drug delivery system (SMEDDS), two solid SMEDDS formulations were prepared by spray-drying the solutions containing liquid SMEDDS and solid carriers. Colloidal silica and dextran were used as a hydrophobic and a hydrophilic carrier, respectively. The liquid SMEDDS, composed of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2% w/v flurbiprofen, gave a z-average diameter of about 100nm. Colloidal silica produced an excellent conventional solid SMEDDS in which the liquid SMEDDS was absorbed onto its surfaces. It gave a microemulsion droplet size similar to that of the liquid SMEDDS (about 100nm) which was smaller than the other solid SMEDDS formulation. In the solid SMEDDS prepared with dextran, liquid SMEDDS was not absorbed onto the surfaces of carrier but formed a kind of nano-sized microcapsule with carrier. However, the drug was in an amorphous state in two solid SMEDDS formulations. Similarly, they greatly improved the dissolution rate and oral bioavailability of flurbiprofen in rats due to the fast spontaneous emulsion formation and the decreased droplet size. Thus, except appearance, hydrophilic carrier (dextran) and hydrophobic carrier (colloidal silica) hardly affected the formation of solid SMEDDS such as crystalline properties, dissolution and oral bioavailability. [Copyright &y& Elsevier]

Abstract: Sustained release (SR) tablets containing solid dispersions (SD) granules of a poorly water-soluble drug were prepared to investigate the controlled pH-independent release of the drug. Losartan potassium (LST), an anti-hypertensive agent was chosen as a model drug because of its pH-dependent solubility and short elimination half-life. Poloxamer 188 was used as an SD carrier. A free-flowing SD granule was prepared by adsorbing the melt of the drug and poloxamer 188 onto the surface of an adsorbent, Aerosil 300 (fumed silicon dioxide), followed by direct compression with polyethylene oxide (PEO, 5×106) to obtain an SD-loaded SR (SD-SR) matrix tablet. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) revealed partially amorphous structures of the drug in the SD granules. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) images indicated adsorption of SD granules onto the surface of the adsorbent. The SD granules dissolved completely within 10min, a dissolution rate much higher than that of pure LST. Moreover, pH-independent sustained release of LST from the SD-SR tablet was achieved for 2h in gastric fluid (pH 1.2) and for 10h in intestinal fluid (pH 6.8). A combination of SD techniques using surface adsorption and SR concepts is a promising approach to control the release rate of poorly water-soluble drugs in a pH-independent manner. [Copyright &y& Elsevier]

Nanoparticle-protein interactions under conditions mimicking physiology determine how nanoparticles (NPs) will behave inside blood vessels and, therefore, the overall outcome of the drug-delivery system. Here, for the first time, we explore the effects of bio-mimicking shear stress and protein corona conditions on novel active targeting of clickable fattigation nanoparticles (NPs) for cancer therapy. Active targeting dibenzocyclooctyne-functionalized biocompatible gelatin-oleic NPs (GON-DBCOs) via a bioorthogonal click reaction were prepared by the desolvation method for delivery of docetaxel (DTX) to lung and breast cancer models. The effect of shear stress (5 dyne/cm2) and human serum albumin (HSA) protein corona on the cellular behavior of NPs was explored under a dynamic microfluidic system in lung (A549) and breast (MCF-7) cancer cell lines. The developed drug-loaded NPs had a particle size of 300 nm, a narrow size distribution, positive zeta potential, high encapsulation efficacy (72.4%), and spherical morphology. The particle size of the protein corona-coated NPs increased to 341 nm with a negative zeta potential. The inhibitory dose (IC 50) increased approximately 3- and 42-fold in A549 and MCF-7 cells, respectively, under dynamic microfluidic conditions compared to static conditions. Cellular uptake was significantly decreased in the presence of shear stress and a protein corona, compared with static conditions, in both lung (A549, **p < 0.01) and breast (MCF-7, *p < 0.05) cancer cell lines. Clathrin-and energy-dependent pathways were found to be involved in the cellular uptake of NPs. This study could serve as a vital tool for the evaluation of NPs under aggressive bio-mimicking conditions comprising shear stress and a protein corona to predict the in vivo performance of NPs and support the preclinical and clinical translation of NP drug delivery systems. Schematic representation of cellular behavior of active targeted nanoparticles in presence of shear stress and protein corona (yellow arrows indicate blood flow shear stress). Unlabelled Image • Protein corona and shear stress mimics the physiological microenvironment. • Docetaxel-loaded gelatin-oleic nanoparticle (GON) actively target the cancer cells by bioorthogonal click chemistry under physiological bio-mimetic conditions. • Observations of this work potentially provide guidance on designing and evaluating nanoparticles for greater clinical relevance. [ABSTRACT FROM AUTHOR]