The Use of Natural Materials in Film Coating for Controlled Oral Drug Release.

BACKGROUND: Although synthetic materials have been used in film coating processes for drug delivery for many years, substantial studies on natural materials have also been conducted because of their biodegradable and unique properties. METHODS: Because of the ability to form and modify films for controlled oral drug delivery, increasing attention has been shown to these materials in the design of film coating systems in recent research. RESULTS: This review aims to provide an overview of natural materials focusing on film coating for oral delivery, specifically in terms of their classification and their combinations in film coating formulations for adjusting the desired properties for controlled drug delivery. CONCLUSIONS: Discussing natural materials and their potential applications in film coating would benefit the optimization of processes and strategies for future utilization.

Design of Zein Conjugation and Surface Modification for Targeting Drug Delivery.

Various strategies for the use of zein for controlled drug release have been investigated and reported in the literature, especially engineering strategies for using zein conjugates to enhance oral bioavailability and targeted delivery, which has attracted interest in recent research. Although still limited, the ability to fabricate self-assembling nanoparticles loaded with molecules of interest offering functional groups for potential conjugation could yield zein-based conjugates with promise as materials for drug delivery. In the current review, recent studies on zein-based conjugates with outstanding features are discussed based on the various types of conjugation. The key physicochemical characterization methods for the chemical conjugation and identification of zein are also summarized. Further opportunities to develop zein-based materials through conjugation will provide promising alternative formulations for a number of drug candidates.

Investigation of Crystallization and Salt Formation of Poorly Water-Soluble Telmisartan for Enhanced Solubility.

The crystal changes and salt formation of poorly water-soluble telmisartan (TEL) in various solvents were investigated for enhanced solubility, stability and crystallinity. Polymorphic behaviors of TEL were characterized by dispersing in distilled water, acetone, acetonitrile, DMSO, or ethanol using Method I: without heat and then dried under vacuum at room temperature; and Method II: with heat below boiling temperature, cooled at 5 °C, and then dried under vacuum at 40 °C. For salt formation (Method III), the following four powdered mixtures were prepared by dispersing in solution of hydrochloric acid (HCl) (pH 1.2), TEL/HCl; in simulated gastric fluid (pH 1.2 buffer), TEL/simulated gastric fluid (SGF); in intestinal fluid (pH 6.8 buffer), TEL/simulated intestinal fluid (SIF); or in NaOH (pH 6.8), TEL/NaOH, respectively, and then dried under a vacuum at room temperature. The structures of powdered mixtures were then studied using a field emission scanning electron microscope (FESEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), FTIR, ¹H nuclear magnetic resonance (¹H-NMR), and LC⁻MS. The solubility of TEL in powdered forms was performed in pH 6.8, pH 1.2, and distilled water. No polymorphic behaviors of TEL were observed in various solvents as characterized by FESEM, DSC, PXRD, and FTIR. However, the structural changes of powdered mixtures obtained from Method III were observed due to the formation of salt form. Moreover, the solubility of salt form (TEL/HCl) was highly increased as compared with pure TEL. There were no significant changes of TEL/HCl compared with TEL in the content assay, PXRD, DSC, and FTIR during stressed storage conditions at 40 °C/75% relative humidity (RH) for 4 weeks under the closed package condition. Therefore, the present study suggests the new approach for the enhanced stability and solubility of a poorly water-soluble drug via salt form.

Fattigation-platform nanoparticles using apo-transferrin stearic acid as a core for receptor-oriented cancer targeting.

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.

Biodistribution and in vivo performance of fattigation-platform theranostic nanoparticles.

This study was aimed at characterizing superparamagnetic nanoparticles surface-functionalized with gelatin-oleic acid (GOAS-MNPs) and loaded with paclitaxel by assessing the pharmacokinetics and biodistribution of paclitaxel in tissues and the in vivo efficacy of antitumor activity after the administration of the drug. Initially, instrumental analysis was performed to examine the particle size distribution, surface charge, and morphology of the paclitaxel-loaded GOAS-MNPs. Furthermore, we evaluated their magnetic properties and performed T2-weighted magnetic resonance imaging (MRI) on cells. We intravenously administered Taxol® and paclitaxel-loaded GOAS-MNPs and compared the pharmacokinetics, biodistribution, and antitumor efficacies of the two formulations. Determination of the pharmacokinetics and the biodistribution of paclitaxel-loaded NPs showed that this formulation increased the systemic circulation time of paclitaxel and regulated its transport to tissues. The in vivo antitumor efficacy of the paclitaxel-loaded NPs was better than that of Taxol® at the same dose. Furthermore, the paclitaxel-loaded GOAS-MNPs were found to be effective as contrast agents for enhanced MRI in cancer cells. Thus, GOAS-MNPs could be an effective diagnostic system for cancer and for the delivery of paclitaxel with better therapeutic effects and a significant reduction in toxicity.

Fattigation-platform theranostic nanoparticles for cancer therapy.

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 T2-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.

Microemulsion-Based Mucoadhesive Buccal Wafers: Wafer Formation, In Vitro Release, and Ex Vivo Evaluation.

Microemulsion has the potentials to enhance dissolution as well as facilitate absorption and permeation of poorly water-soluble drugs through biological membranes. However, its application to govern a controlled release buccal delivery for local treatment has not been discovered. The aim of this study is to develop microemulsion-based mucoadhesive wafers for buccal delivery based on an incorporation of the microemulsion with mucoadhesive agents and mannitol. Ratio of oil to surfactant to water in the microemulsion significantly impacted quality of the wafers. Furthermore, the combination of carbopol and mannitol played a key role in forming the desired buccal wafers. The addition of an extra 50% of water to the formulation was suitable for wafer formation by freeze-drying, which affected the appearance and distribution of carbopol in the wafers. The amount of carbopol was critical for the enhancement of mucoadhesive properties and the sustained drug release patterns. Release study presented a significant improvement of the drug release profile following sustained release for 6 h. Ex vivo mucoadhesive studies provided decisive evidence to the increased retention time of wafers along with the increased carbopol content. The success of this study indicates an encouraging strategy to formulate a controlled drug delivery system by incorporating microemulsions into mucoadhesive wafers.

Sonication-Assisted Nanoprecipitation in Drug Delivery.

Sonication-assisted nanoprecipitation provides an effective tool for nanomedicine engineering in therapeutic improvement. In the scope of this review, original works in interdisciplinary areas of using sonication with precipitation method for nanoparticulate drug delivery systems and its applications in management of different diseases are discussed. The use of sonication-assisted nanoprecipitation has been proved to improve drug bioavailability, which attracts tremendous interests as an effective strategy for drug delivery. However, many challenges still remain. To overcome these barriers, different approaches such as precipitation method, rational design, optimization and modification have been investigated. Accordingly, current knowledge of sonication-assisted nanoprecipitation proposes a broad perspective and optimization for the applications of nanotechnology in drug delivery.

Strategies of Engineering Nanoparticles for Treating Neurodegenerative Disorders.

BACKGROUND: Neurodegenerative disorders (NDs) are typically referred to Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis and prion disease. These are commonly debilitating and, unfortunately, have few therapeutic options. OBJECTIVE: In this review, we describe some emerging advances in nanoengineering strategies for the treatment of NDs. One of the main difficulties in fighting against NDs is to overcome the shielding of blood-brain barrier (BBB), which greatly limits the penetration of various therapeutic drugs, which sometimes leads to severe side effects. Nanotechnology, by engineering materials of a size scale usually within 1-100 nm, fortunately offers an alternative approach for novel, promising and innovative solutions. Nanoparticles are capable of not only penetrating the BBB but also releasing active ingredients at a specific site due to its surface functionalization. Therefore, nanoengineered delivery systems potentially facilitate the targeted delivery of neuronal therapeutic drugs and genes to the central nervous system. Furthermore, recently developed nanomaterials are considered as therapeutic agents themselves since they exhibit important roles in promoting the protection of healthy neurons or the regeneration of neurons to repair damaged tissues. CONCLUSION: There have been a variety of innovative approaches to designing therapeutic nanoparticles for NDs, and each has been associated with certain pros and cons.

Hydrophilic-hydrophobic polymer blend for modulation of crystalline changes and molecular interactions in solid dispersion.

This research study aimed to develop a new strategy for using a polymer blend in solid dispersion (SD) for dissolution enhancement of poorly water-soluble drugs. SDs with different blends of hydrophilic-hydrophobic polymers (zein/hydroxypropyl methylcellulose - zein/HPMC) were prepared using spray drying to modulate the drug crystal and polymer-drug interactions in SDs. Physicochemical characterizations, including power X-ray diffraction and Fourier transform infrared spectroscopy, were performed to elucidate the roles of the blends in SDs. Although hydrophobic polymers played a key role in changing the model drug from a crystal to an amorphous state, the dissolution rate was limited due to the wetting property. Fortunately, the hydrophilic-hydrophobic blend not only reduced the drug crystallinity but also resulted in a hydrogen bonding interaction between the drugs and the polymer for a dissolution rate improvement. This work may contribute to a new generation of solid dispersion using a blend of hydrophilic-hydrophobic polymers for an effective dissolution enhancement of poorly water-soluble drugs.

An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice.

The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH6.8 at 37±0.5°C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug.

Design of Fucoidan Functionalized - Iron Oxide Nanoparticles for Biomedical Applications.

This research aims to develop an iron oxide nanoparticle drug delivery system utilizing a recent material discovered from ocean, fucoidan. The material has drawn much interest due to many biomedical functions that have been proven for human health. One interesting point herein is that fucoidan is not only a sulfated polysaccharide, a polymer for stabilization of iron oxide nanoparticles, but plays a role of an anticancer agent also. Various approaches were investigated to optimize the high loading efficiency and explain the mechanism of nanoparticle formations. Fucoidan was functionalized on iron oxide nanoparticles by a direct coating or via amine groups. Also, a hydrophobic part of oleic acid was conjugated to the amine groups for a more favorable loading of poorly water-soluble anticancer drugs. This study proposed a novel system and an efficient method to functionalize fucoidan on iron oxide nanoparticle systems which will lead to a facilitation of a double strength treatment of cancer.

Nano-Precipitation: Preparation and Application in the Field of Pharmacy.

Over the last 30 years, nanoparticle-based medicine has received tremendous attention due to its advances with smart therapeutics and less toxicity. Few nanomedicine products have been approved for commercial use in the clinic (such as Doxil(®), Ambraxane(®)..). Nanomedicine research is still at its early stage and the preparation of nanoparticles must be carefully considered. Systems involving further increased supersaturation, either via solvent evaporation, temperature reduction or anti-solvent mixture, were suggested to be capable of inducing nanoprecipitation (NPT). Since this technique is straight-forward, fast and easy to duplicate in practice, it is highly preferred and recommended. In this review, the process of NTP was described and discussed in detail. Factors that affect the encapsulation efficiency, the nanoparticle size, the morphology and the stability of nanoparticles prepared by NTP were described. This process is one of the most preferable processes for preparing solid nano-protein due to their elegant techniques that preserve the bioactivity of proteins. Although the production of nanoparticles by this process has not been applied in the pharmaceutical industry due to the organic solvent issue, the production equipment for large-scale has been marketed.

Nanoparticulate Drug Delivery to Colorectal Cancer: Formulation Strategies and Surface Engineering.

The evolution of polymer-based nanoparticle as a drug delivery carrier has greatly contributed to the development of advanced nano and micro-medicine in the past few decades. The polymer-based nanoparticles of biodegradable and biocompatible polymers such as poly (lactide-co-glycolide) and chitosan which have been approved by Food & Drug Administration and/or European Medicine Agency can particularly facilitate the maintaining of specific properties for a real transition from laboratory to the clinical oral and parental administration. This review presents an overview of the strategies of preparing polymeric nanoparticles and using them for targeting colorectal cancer. Theranostics and surface engineering aspects of nanoparticle design in colonic cancer delivery are also highlighted.

Perspectives of Engineered Marine Derived Polymers for Biomedical Nanoparticles.

Marine environment exhibits an enormous diversity of organisms which contains an abundant source of polysaccharides. As polymer matrix carriers, marine-based polymers possess several valuable properties including high stability, non-toxicity, hydrophilicity, biodegradability, with low production cost. Despite notable biological activities of these natural polymers, there are certain limitations in exploring their functions in applications of nano-sized drug delivery systems. The review aims to demonstrate exceptional characteristics of marine-based polymers including fucoidan, alginate, carrageenan, hyaluronic acid, chondroitin sulfate, and chitosan as well as provide perspectives of current publications on their nanoparticle formulations for biomedical applications.

Design of sustained release tablet containing fucoidan.

The study introduced a new therapeutic agent, fucoidan, which can offer potential medical treatments including anti-inflammatory and anti-coagulant activities, as well as anti-proliferative effects on cancer cells. Fucoidan was included in sustained release formulations expected for an effective plasma drug concentration for approximately 24 h. The matrices based on the two polymers hydroxypropyl methycellulose (HPMC) and polyethylene oxide (PEO) were prepared with various ratios between the polymers and fucoidan. The dissolution profiles of various matrix tablets performed in enzyme-free simulated intestinal fluid (pH 6.8) for 24 h indicated a higher potential of PEO-based matrix tablets in sustaining release of fucoidan. The swelling and erosion of the tablets were also characterized to elucidate the difference among those dissolution profiles.

Modulation of particle size and molecular interactions by sonoprecipitation method for enhancing dissolution rate of poorly water-soluble drug.

Aim of present work was to originally elucidate the roles of ultrasonication method for modulating the size and molecular interactions in controlling release of poorly water-soluble drug. Curcumin was chosen as a model drug. Three types of polymers were investigated as carriers for preparation of polymeric nanoparticles under various ultrasonication conditions and polymer-drug ratios. Changes in drug crystallinity, particle size, and molecular interactions which would be factors enhancing drug dissolution rate were evaluated. Amorphous form of curcumin, size reduction of nanoparticles and interaction between drug and polymer in formulations were attributed to improved drug dissolution rate. Particle size was strongly affected by polymer type, polymer-drug ratio and ultrasonication conditions. Interestingly, control of those factors caused differences in molecular interactions of the hydroxyl groups and then, highly affected particle size of the nanoparticles. It was obvious that there was a reciprocal influence between the drug-polymer interactions and particle size of the nanoparticles. This relation could be modulated by polymers and ultrasonication processes for enhancing drug dissolution rate.

Amorphous isradipine nanosuspension by the sonoprecipitation method.

The aims of this study are to increase and explain the mechanism of dissolution enhancement of isradipine using the sonoprecipitation method for stable nanosuspensions. There have been still few of published researches on formulation of isradipine using nanoparticle engineering. Nanosuspension systems were prepared upon various factors including amplitude and the time length of ultrasonication. The dissolution test was performed according to the USP paddle method in intestinal fluid (pH 6.8). The crystalline structure of drug, the molecular interaction, morphology and size of nanosuspension were also investigated to determine the mechanism of dissolution enhancement. The sonoprecipitation method with use of HPMC 6 showed its potential in enhancement of the drug release rate. Stable nanosuspension was significantly depended on amplitude and time of ultrasonication since these factors affected on the size of nanoparticles. The synergistic effects of reduction of drug crystallinity and particle size could increase the dissolution rate of isradipine by providing a stable nanosuspension. This work may contribute to a new strategy for improvement dissolution rate of isradipine.

Polymer conjugate-based nanomaterials for drug delivery.

The structure of polymeric amphiphiles with both hydrophilic and hydrophobic groups forming self-assembled nanoparticles have attracted increasing attention in studies of delivery systems of therapeutic agents. An amphiphilic carrier for self-assembly in an aqueous solution is preferable because of its structure with a hydrophobic core and hydrophilic outer shell, which can be applied to many biotechnological and pharmaceutical fields with numerous types of drugs. An amphiphilic carrier for self-assembly also represents the most appealing delivery system owing to its exceptional advantages in selectively delivering drugs to tumor cells and thus, reduction of side effects. This paper reviews two types of self-assembled nanoparticles/micelles of conjugated polymeric amphiphiles: (1) self-assembled micelles/nanoparticles of amphiphilic conjugates followed by drug loading and (2) self-assembled micelles/nanoparticles of polymer-drug conjugates where a conjugation reaction occurs between the polymer and drug. The development of the research has been addressed in this review with up-to-date references. In conclusion, the challenges and remaining difficulties for the future development are discussed.

Biodistribution and pharmacokinetics in rats and antitumor effect in various types of tumor-bearing mice of novel self-assembled gelatin-oleic acid nanoparticles containing paclitaxel.

The aim of this study was to investigate the pharmacokinetics and biodistribution in Sprague-Dawley rats, anti-tumor activity and acute toxicity in different tumor-bearing mice of novel biocompatible nanoparticles. Paclitaxel (PTX) was selected as a model drug and loaded on different tumor types and at various doses. The nanoparticles were prepared using a newly synthesized gelatin-oleic acid conjugate via self-assembly in an aqueous solution. The nanoparticles were further functionalized using folic acid (FA) as a targeting ligand for cancer. The in vivo effects of the nanoparticles were compared with the commercially available Taxol (a solution form of PTX) as a reference dosage form. The in vivo studies confirmed that nanoparticles showed improved therapeutic effects on tumors and significantly reduced the toxic effects associated with Taxol, even at the 50% lethal dose (LD50). The in vivo pharmacokinetic parameters and biodistribution of the nanoparticles containing PTX also indicated slower clearance, longer blood circulation and higher tumor selectivity. Furthermore, the functionalized nanoparticles with FA were more effective than the non-functionalized nanoparticles. Thus, the suitable properties of gelatin-oleic nanoparticles (GON) as a drug carrier and the effective targeting ligand could synergistically maximize the in vivo anti-tumor efficacy resulting in delayed tumor volume growth and hence, providing versatile strategies in cancer therapy and drug delivery.