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Background: This study aimed to evaluate the effects of hydrophobic and hydrophilic Film-Forming Gels (FFGs) on the controlled delivery of drugs with different levels of hydrophobicity. Methods: This evaluation was carried out by employing zein and polyvinylpyrrolidone as hydrophobic and hydrophilic film-forming agents, respectively, in combination with hydroxypropyl methylcellulose functionalized as a hydrogel basement at a ratio that had been optimized to achieve the fastest drying time. Free curcumin or terbinafine hydrochloride was subsequently dispersed into blank FFGs to produce the final FFG formulations. Results: Although the extreme hydrophobicity of curcumin strongly limited its topical permeability compared to that of terbinafine hydrochloride, zein FFGs clearly resulted in a favourable sustained release system for highly hydrophobic drugs, such as curcumin. Moreover, polyvinylpyrrolidone would be highly effective for the sustained release of a less hydrophobic drug, such as terbinafine hydrochloride. Analyses of the wettability, surface morphology, chemical interactions and crystallinity of FFGs also helped to elucidate the mechanisms of their drug release profiles. Conclusion: This fundamental finding is beneficial for further design studies on FFGs as sustained drug delivery systems for topical drugs with a wide range of hydrophobicities.

Aspirin has emerged as a promising intervention in cancer in the past decade. However, there are existing controversies regarding the anticancer properties of aspirin as its mechanism of action has not been clearly defined. In addition, the risk of bleeding in the gastrointestinal tract from aspirin is another consideration that requires medical and pharmaceutical scientists to work together to develop more potent and safe aspirin therapy in cancer. This review presents the most recent studies of aspirin with regard to its role in cancer prevention and treatment demonstrated by highlighted clinical trials, mechanisms of action as well as approaches to develop aspirin therapy best beneficial to cancer patients. Hence, this review provides readers with an overview of aspirin research in cancer that covers not only the unique features of aspirin, which differentiate aspirin from other non-steroidal anti-inflammatory drugs (NSAIDs), but also strategies that can be used in the development of drug delivery systems carrying aspirin for cancer management. These studies convey optimistic messages on the continuing efforts of the scientist on the way of developing an effective therapy for patients with a low response to current cancer treatments.

Solid dispersions offer many advantages for oral drug delivery of poorly water-soluble drugs over other systems, including an increase in drug solubility and drug dissolution. An improvement in drug absorption and the higher bioavailability of active pharmaceutical ingredients in the gastrointestinal tract have been reported in various studies. In certain circumstances, a rapid pharmacological effect is required for patients. Fastdissolving solid dispersions provide an ideal formulation in such cases. This report will provide an overview of current studies on fast-dissolving solid dispersions, including not only solid dispersion powders with fast dissolution rates but also specific dose form for the controlled release of poorly water-soluble drugs. Specifically, the applications of fast-dissolving solid dispersions will be described in every specific case. Moreover, pharmaceutical approaches and the utilization of polymers will be summarized. The classification and analysis of fastdissolving solid dispersions could provide insight into strategies and potential applications in future drug delivery developments.

Mucoadhesive formulations have been demonstrated to result in efficient drug delivery systems with advantages over existing systems such as increased local retention and sustained drug release via adhesiveness to mucosal tissues. The controlled release of colon-targeted, orally administered drugs has recently attracted a number of studies investigating mucoadhesive systems. Consequently, substantial designs, from mucoadhesive cores to shells of particles, have been studied with promising applications. This review will provide an overview of specific strategies for developing mucoadhesive systems for colon-targeted oral delivery with controlled drug release, including mucoadhesive matrices, cross-linked mucoadhesive microparticles, coatings and mucoadhesive nanoparticles. The understanding of the basic principle of these designs and advanced formulations throughout will lead to the development of products with efficient drug delivery at the colon for therapies for different diseases.

Aims: The purpose of this study was to investigate and compare the formation of polymeric and Ocimum gratissimum seed films containing solid lipid particles for controlled drug release. Methods: The hot homogeneous method was selected to form solid lipid particles containing sodium fusidate to load the drug into the film. The in vitro drug release and drug permeability of the films were tested with dialysis tubes and the Franz diffusion cell method, respectively. The mucoadhesive time and swelling and erosion rates were also studied. Results: The solid lipid particles showed the ability to form Ocimum gratissimum seed and polymeric films for use in drug delivery. Although the polymeric matrix yielded excellent swelling and erosion rates, leading to a faster drug release rate and drug permeation than that of the Ocimum gratissimum seed film, the mucoadhesive time of the polymer film was worse than that of the seed film. Conclusion: Therefore, the characteristics of the individual systems may be further studied in a combined system to take full advantage of both in the desired film.

It has been well established that solid dispersions have a high potential to increase the release rate of poorly water-soluble drugs, resulting in high drug bioavailability. Solid dispersions have been vigorously investigated with various practical approaches in recent decades. Improvements in wettability, molecular interactions and drugs being held in an amorphous state in solid dispersions are the main mechanisms underlying the high drug release rate. Moreover, the synergistic effect of incorporating nanotechnology in solid dispersions is expected to lead to an advanced drug delivery system for poorly water-soluble drugs. However, to date, there is still a lack of reviews providing outlooks on the nano-sized solid dispersions that have been substantially investigated for improving the bioavailability of poorly water-soluble drugs. In the current review, we aim to overview key advantages and approaches for producing nano-sized solid dispersions. The classification of key strategies in developing nano-sized solid dispersions will advance the creation of even more efficient solid dispersions, which will translate into clinical studies.

Background: Natural materials have been encouraged in controlled drug release and improved drug bioavailability. Objective: This study aimed to develop a modification process for the use of a natural material, Ocimum gratissimum seeds (OGS), in Orally Disintegrating Tablets (ODTs). Methods: The OGS was investigated with four different modification processes including only milling, swelling, swelling/milling, and swelling/milling/incubation. The ODTs containing the modified OGS as a disintegrant were prepared by the wet granulation method. Furthermore, an evaluation to assess parameters of tablets, such as weight variation, hardness, friability, wetting time, disintegration time, drug content, and dissolution studies, was performed. Results: The modification of OGS using the swelling/ milling process resulted in a completion of OGS modification, leading to an ideal wetting time, disintegrating time, and dissolution rate. The OGS concentrations also affected the wetting and disintegrating time with the optimal range of ODTs from 15% to 20%. On the other hand, the modification with the incubation processes varied by temperature and time increased the wetting time and disintegrating time. Conclusions: The modified OGS demonstrated that it is a potential material with the advantages of cost-effectiveness, non-toxicity and easy manufacture in the preparation of ODTs.

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.

Improving drug bioavailability in the pharmaceutical field is a challenge that has attracted substantial interest worldwide. The controlled release of a drug can be achieved with a variety of strategies and novel materials in the field. In addition to the vast development of innovative materials for improving therapeutic effects and reducing side effects, the exploration of remarkable existing materials could encourage the discovery of diverse approaches for adapted drug delivery systems. Recently, superdisintegrants have been proposed for drug delivery systems as alternative approaches to maximize the efficiency of therapy. Although superdisintegrants are well known and used in solid dosage forms, studies on strategies for the development of drug delivery systems using superdisintegrants are lacking. Therefore, this study reviews the use of superdisintegrants in controlled drug release dosage formulations. This overview of superdisintegrants covers developed strategies, types (including synthetic and natural materials), dosage forms and techniques and will help to improve drug delivery systems.

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.

Background: Natural nanostructure materials have been involved in antitumor drug delivery systems due to their biocompatibility, biodegradation, and bioactive properties. Methods: These materials have contributed to advanced drug delivery systems in the roles of both bioactive compounds and delivery nanocarriers. Fucoidan, a valuable ocean material used in drug delivery systems, has been exploited in research on cancer and a variety of other diseases. Results: Although the uniqueness, structure, properties, and health benefits of fucoidan have been mentioned in various prominent reviews, current developments and designs of fucoidan-based formulations still need to be assessed to further develop an effective anticancer therapy. In this review, current important formulations using fucoidan as a functional material and as an anticancer agent will be discussed. This article will also provide a brief principle of the methods that incorporate functional nanostructure materials in formulations exploiting fucoidan. Conclusion: Current research and future perspectives on the use of fucoidan in anticancer therapy will advance innovative and important products for clinical uses.

This study aims to develop mucoadhesive tablets containing solid lipid particles for controlled release pattern through buccal delivery. The buccal tablets containing drug-loaded solid lipid particles (SLPs) were fabricated using the ultrasonication method and lyophilisation with the incorporation of bioadhesive excipients. The role of stearic acid in the lipid phase and the effects of different surfactant contents were thoroughly evaluated. The stearic acid in formulations showed its impacts on particle formation and release characteristics. Although liquid surfactants could create SLPs of nano-size, the dissolution profile resulted in low drug release. The combination of a solid surfactant and a liquid surfactant resulted in better tablet formation and an improvement in the dissolution rate of prednisolone in both immediate release and sustained release. Furthermore, an adaptable pH surface, long mucoadhesion time, and satisfactory permeation resulted in suitable conditions for buccal tablet design without causing any irritations. The success of this work could contribute to a new strategy for improving the bioavailability of poorly water-soluble drugs by buccal delivery.

Although zein is a natural protein derived from corn, it has attracted much interest in pharmaceutical and biomedical sciences. Recent remarkable investigations on the use of zein in controlled drug delivery have contributed both important knowledge and potential applications of various products, particularly in the delivery of poorly water-soluble drugs. Zein has also been approved by the Food and Drug Administration for oral delivery. Substantial research has been performed to demonstrate the roles and promise of materials containing zein for pharmaceutical applications. Significant efforts have focused on the biodegradable and hydrophobic properties of zein and on technology using zein as a nanocarrier specifically for nanomedicine. However, important issues concerning the use of zein in technical advances and in the development of poorly water-soluble drugs must be addressed in order to use zein in translational research. This review aims to focus on the classification of potential approaches for using zein in the controlled release of poorly water-soluble drugs and to discuss recommended techniques for creating high-quality products from zein.

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.

The aim of this study was to investigate the impact of different chain length fatty acids on physicochemical properties and cancer targeting of fattigation-platform nanoparticles (NPs). Two different types of fatty acids (short chain, 2-hydroxybutyric acid, C4; long chain, oleic acid, C18:1) were successfully conjugated to human serum albumin (HSA) via simple 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling reaction. These conjugates readily formed HSA-C4 and HSA-C18:1 NPs which showed good stability in serum and desirable biocompatibility with normal cell line (HEK293T). Doxorubicin hydrochloride (DOX) was efficiently loaded into NPs by incubation process via electrostatic interaction. The structure, morphology, and texture of DOX-loaded NPs were characterized by Transmission electron microscopy (TEM) equipped with Energy-dispersive X-ray spectroscopy (EDS). The initial burst release of DOX-loaded NPs was controlled by the presence and chain length of fatty acids. In vitro cytotoxicity studies with three cancer cell lines (A549, HT-29, and PANC-1) suggested that fattigation-platform NPs have distinctive cytotoxic effects compared to Doxil®. Confocal microscopy and flow cytometry exhibited that the cellular uptake of DOX-loaded NPs was varied by the different chain lengths of fatty acids. It was evident that the chain length of fatty acids in the fattigation-platform NPs could play a vital role in varying physicochemical properties and cancer cell targeting of NPs.

BACKGROUND: The mucoadhesive polymers play an important role in targeted and controlled drug delivery. OBJECTIVES: This study aimed to investigate the drug release behaviour and interpret the role of mucoadhesive polymers involved in the coating layer of mucoadhesive tablets for the sustained release of a poorly water-soluble drug. METHODS: A solid dispersion of prednisolone and zein was used in the core tablets created with two mucoadhesive polymers, which included Carbopol 940 and hydroxypropyl methylcellulose K4M. In addition, the properties of a single-layer coating, created from the combination of zein and Kollicoat MAE 100P to delay release through the upper parts of the gastrointestinal tract, were investigated in the presence of the above mucoadhesive polymers; these properties included drug dissolution, mucoadhesion, surface morphology, swelling and erosion. RESULTS: The mucoadhesive polymer concentrations and types were integrated not only into the core tablets through a swelling/erosion mechanism but also into the surface polymer coatings for controlled drug release. HPMC was preferred in the formulations due to the ability to form pores on the surface coating, allowing water uptake so that the coating could control drug release for a later stage via a swelling/erosion mechanism. CONCLUSION: The proposed mechanism determined in this project could be beneficial in the selection of polymers for applications targeting the colon with coated mucoadhesive tablets. [Figure: see text]

Background: Mucoadhesive polymers play a critical role in controlled-release tablets for buccal drug delivery. Objective: This research aimed to investigate the characterization and mechanisms of solid lipid particle-based tablets with different mucoadhesive polymers for buccal delivery. Methods: Prednisolone (PSL)-loaded solid lipid particles (SLPs) were conventionally prepared by ultrasonication. The freeze-drying method was used to convert the SLP suspension into a solid dosage form for buccal delivery by using mucoadhesive polymers. Results: All formulations showed over 80% drug release after 6 h, which followed immediate and sustained release patterns depending on the SLP type. However, the different polymers in the formulations resulted in different mucoadhesion times and drug release and drug permeability profiles. HPMC 4000 showed higher drug permeation (3327 μg vs. 2589 μg after 6 h) but a shorter mucoadhesion time than Carbopol (197 min vs. 361 min). In addition, surface morphology, swelling and erosion, particle size and zeta potential were also noted for the different mechanisms for buccal tablet design with different controlled release profiles. Conclusion: The results of this work indicate a good strategy for the selection of mucoadhesive polymers for SLP-based tablets in improving the bioavailability of poorly water-soluble drugs.

The objective of this study was to achieve an optimal formulation of hydrophilic-hydrophobic conjugates for nano-sized solid dispersions (SDs) with enhanced dissolution of multiple drugs in different gastrointestinal (GI) tract environments. A new conjugate powder with an optimized process was used to fabricate SDs that contained three poorly water-soluble drugs that were also poorly soluble in different dissolution media. The self-assembled nanoparticle formation, drug crystallinity and SD molecular interactions were investigated by measuring the particle size during dissolution testing and physicochemical property analysis (powder X-ray diffraction and Fourier transform infrared spectroscopy). Drug release studies indicated that SD containing conjugated powder significantly improved the dissolution rates of these poorly water-soluble drugs in the GI tract. In addition, particle size analysis showed nano-sized particles in the dissolution media in the early stage with a tendency to reduce smaller particles over time. Physicochemical characterizations demonstrated almost amorphous drug states and hydrogen bonding interactions between the drugs and conjugates in the SD. This study optimized a promising material for SD, and the material was shown to have a promising performance under various pH medium conditions with poorly water-soluble drugs.

Background: The aim of this study was to develop and compare polymeric micelles of fucoidan, a sulfated polysaccharide, and hydrophobic drugs such as paclitaxel and curcumin. Paclitaxel and curcumin are both known for their medicinal properties, including anticancer efficacy. However, their very low water solubility, absorption and rapid metabolism leads to reduced bioavailability. To redress these problems and enhance anti-cancer therapeutics using fucoidan, polymeric micelles were synthesized from conjugates of fucoidan and hydrophobic drugs. Methods: The chemical conjugation of fucoidan and hydrophobic drugs has been achieved by utilizing reactive functional groups on the molecules, such as carboxylic groups and hydroxyl groups. Results: The micelles revealed a homogeneous spherical morphology, size, negative surface charge. Fourier transform infrared spectroscopy was used to investigate the physicochemical properties of the polymeric micelles, which form a self-assembled polymeric micelle in aqueous medium. The results of the in vitro release of curcumin and fucoidan showed that their release rates were higher at a pH of 4.5 than at a pH of 7.4. In contrast, the paclitaxel conjugate had a similar release profile at pH of 4.5 and pH of 7.4. Conclusion: In the present work, we also found an effective drug delivery system that had the ability to release two types of anticancer drugs, fucoidan and hydrophobic drugs, in the tumour environment.

Albumin is the most abundant protein in blood, and is the most frequently identified protein in the protein corona of nanoparticles (NPs). Thus, albumin plays an important role in modulating NPs' physicochemical properties and bioavailability. In this study, the effect of bovine serum albumin (BSA) on gelatin-oleic nanoparticles' (GONs) physicochemical properties and cellular uptake were evaluated. Coumarin-6 was used as indicator to track the cellular uptake of GONs. The binding of BSA onto the GON surface increased the size, slightly reduced the negative net charge of the GON, and improved GON stability. The presence of BSA in cell culture media reduced the cellular uptake of BSA-uncoated GONs on human embryonic kidney cells 293 (HEK 293) and human adenocarcinoma alveolar basal epithelial cells (A549) in the media without FBS addition. Pre-coated BSA corona decreased cellular uptake of GONs in A549 cells in the media, with and without supplemented with 10% fetal bovine serum (FBS) but drastically increased cellular uptake on HEK 293 cells. BSA could be used to modulate protein corona as an endogenous ligand in NP design simply by mixing or incubating BSA with NPs before in vivo administration to inhibit or induce cellular uptake in specific cell types.

The aims of this work were to design pH-independent controlled release (CR) tablet containing nanonizing solid dispersion (SD) adsorbed on hydrophilic silica (Aeroperl® 300/30). Valsartan (VAL) was chosen to simultaneously modulate solubility and release rate due to its poor water solubility in low pH condition and short elimination half-life. Based on extensive equilibrium solubility and compatibility studies, poloxamer 407 was selected as a SD carrier. The melted mixtures of drug and poloxamer 407 were adsorbed onto hydrophilic fumed silica (Aeroperl® 300/30). Ternary SD system changed crystalline drug into an amorphous state and had intermolecular hydrogen bonding as confirmed by FT-IR with poloxamer 407. The dissolution rate of SD system was markedly enhanced as compared with pure VAL or commercial Diovan® tablet in simulated gastric fluid (pH 1.2). Interestingly, the particle size of SD system was gradually nanonized for 2 hr, ranging from 600 nm to 150 nm during dissolution process. The SD-loaded CR (SD-CR) tablets using hydroxypropylmethylcellulose (HPMC 4000) showed pH-independent zero-order release and good stability at accelerated conditions for six months. The SD-CR tablet showed minimized inter-subject variation of maximum plasma concentration as compared with commercial Diovan® tablets in healthy human volunteers.

Sprouted grains, which is a natural polysaccharide, is the subject of increasing scientific interest due to many benefits for human health. The aim of the present work was to develop sprouted rice (SR) as a safe and useful material for application in dissolution enhancement of anticancer poorly water-soluble drugs such as curcumin by solid dispersions (SDs). SDs were prepared with pure SR and modified sprouted rice (MSR) by the melting method. The dissolution rate, drug crystallinity changes, molecular interactions and wettability were characterized and compared between the formulations. The use of MSR could result in a promising system for improving the dissolution rate of poorly water-soluble drugs. MSR could induce a greater amorphous state and improved wettability of drugs for dissolution enhancement compared to SR. Although both SR and MSR showed hydrogen bonding interaction, insignificant differences between SR and MSR were observed. We found that the crystallinity, interactions and wettability of the drug were significantly affected and modulated by MSR.

Background Efficient colon-specific drug delivery has been demonstrated recently in the treatment of various diseases, including Crohn's disease, ulcerative colitis (inflammatory bowel disease), and colorectal cancer. Methods Of all strategies, the conjugation of a model drug to a carrier (with or without spacers) has been recognized as promising for targeting the colon. Results This is because the conjugation method releases large amounts of the drug while reducing the amount of the drug released in the stomach and small intestine. Conclusion This review focuses on the design of linkage conjugates that carry out specific delivery to the colon. The types of conjugation for application in colorectal cancer therapy will be discussed as well.

Poorly water-soluble drugs, which commonly face the issue of poor absorption and low bioavailability, have been under ongoing research of many formulation scientists for the past few decades. Solid dispersion is one of the most effective strategies in concerns for improving bioavailability of poorly water-soluble drugs. Either application of solid dispersions in dissolution enhancement of poorly water-soluble drugs or the use of swellable polymers in controlled drug release has been reported in pharmaceutical designs widely. However, a review of strategies of using swellable polymers in solid dispersion to take a full advantage of these polymers as a current perspective in facilitating drug bioavailability enhancement is still missing. In this review, we aim to provide a summary of techniques used to formulate a swellable polymer in solid dispersion especially a description of a suitable fabrication method in design of a controlled release solid dispersion.

Gene therapy has a strong potential in neuroscience by suppressing or replacing abnormalities in genetic materials. The employment of nano-gene carrier for neurological disorders is comparatively young and restricted since the aim to effectively deliver therapeutic agents into the central nervous system (CNS) commonly has confronted difficulties of several natural occurring barriers in the body and unfavorable characteristics of pharmaceutical agents. Two major anatomical and biochemical barriers are blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), which significantly prevent permeation of most drugs and genes to brain parenchyma. In this concern, nanotechnology emerges as an innovative method for transporting therapeutics to the CNS. Diverse nano-systems have been closely investigated, some of which have demonstrated initial success for in vivo studies. The perspectives of nanotechnology for gene therapy would be a promising field to be further explored in the near future.

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. Conclusion: Discussing natural materials and their potential applications in film coating would benefit the optimization of processes and strategies for future utilization.

Targeted exosomal delivery systems for precision nanomedicine attract wide interest across areas of molecular cell biology, pharmaceutical sciences, and nanoengineering. Exosomes are naturally derived 50-150 nm nanovesicles that play important roles in cell-to-cell and/or cell-to-tissue communications and cross-species communication. Exosomes are also a promising class of novel drug delivery vehicles owing to their ability to shield their payload from chemical and enzymatic degradations as well as to evade recognition by and subsequent removal by the immune system. Combined with a new class of affinity ligands known as aptamers or chemical antibodies, molecularly targeted exosomes are poised to become the next generation of smartly engineered nanovesicles for precision medicine. Here, recent advances in targeted exosomal delivery systems engineered by aptamer for future strategies to promote human health using this class of human-derived nanovesicles are summarized.

Background:: An increase in poorly water-soluble drugs makes the design of drug delivery systems challenging. Methods:: Currently, a number of prospective solid dispersions have been investigated with potential applications for delivering a variety of poorly water-soluble drugs. A number of traditional solid dispersions and modifiedsolid dispersions offer attractive advantages in the fabrication, design and development of those drugs for effective therapeutics. Results:: Although traditional solid dispersions can produce a higher release rate, resulting in higher bioavailability compared to conventional dosage forms, this method is not always a promising approach. Modified-solid dispersion has demonstrated both the ability of its polymers to transform drug crystals into amorphous forms and molecular interactivity, thereby improving drug dissolution rate and bioavailability, especially with tough drugs. However, the classification of modified-solid dispersion, which guides the selection of the right strategy in solid dispersion preparation, remains ill-defined. Conclusions:: This review focused on effective strategies in using additives in solid dispersion for improving drug bioavailability.

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 &deg, C, and then dried under vacuum at 40 &deg, 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&ndash, 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 &deg, 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.

This study aimed to originally investigate the roles of a surfactant in hydrophilic-hydrophobic polymer blend solid dispersions (SDs) to enhance drug dissolution. Different formulations of SDs containing a hydrophilic polymer, a hydrophobic polymer or a hydrophilic-hydrophobic blend were prepared with/without surfactant, and the crystal changes, wettability, and molecular interactions were investigated. The wettability was investigated by analysing the contact angle. Powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy were used to study the physicochemical properties of the SDs. This study showed that the surfactant improved the wettability of hydrophilic-hydrophobic blend SDs. Moreover, the incorporation of the surfactant led to the minimization of drug crystals in SDs. In particular, the surfactant showed an effectiveness in drug crystalline changes with hydrophobic polymers compared to hydrophilic polymers. The maximization of reducing drug crystals was observed in an optimized blending ratio of hydrophilic-hydrophobic polymers. This result indicated that the surfactant played a key role in assisting a hydrophilic-hydrophobic polymer blend, which has been demonstrated as a dominant strategy for SDs, to enhance the dissolution rate of a poorly water-soluble drug.

Background: Recently, several strategies have been proposed for skin cancer therapy by transdermal delivery, and particularly the use of nanotechnology. Methods: This process disrupts the stratum corneum to deliver a drug through the skin, allowing it to accumulate at the tumor site. Results: Nanogels are drug delivery systems that can be applied to many diseases. Nanogel engineering has been widely studied for use in drug delivery, particularly in cancer theranostics. This review summarizes specific strategies for using nanogels to treat skin cancer, a topic that is limited in recent literature. Conclusion: Advanced techniques for effective skin cancer therapy based on the nanogel’s penetration and cellular uptake abilities will be discussed. Moreover, techniques for penetrating the skin, as well as drug release, permeation studies, and microscopic observations, will also be discussed.

Although solid dispersions have been reported as an efficient drug delivery system, the design of specific dosage forms for pharmaceutical therapy is necessary to improve the solubility and bioavailability of poorly water-soluble drugs. Solid dispersions can be incorporated in general solid dosage forms such as powders, granules, capsules and tablets, but only to enhance solubility and the dissolution rate. However, further development of solid dispersions will be required in certain circumstances for further in vivo drug improvement of those solid dosage forms. In the current review, specific designs of solid dosage forms for controlled drug release will be reported. Moreover, methods and strategies for incorporating these solid dispersions into controlled drug release forms will also be discussed. Overall, the outlook of current studies will provide potential approaches for the further improvement of solid dispersions, especially for clinical developments in pharmaceutical therapy.

In the current study, we developed interpolymer-complex structures composed of hydroxypropyl methylcellulose (HPMC) and chitosan knitted with d-α-tocopherol polyethylene glycol succinate (TPGS) to establish oral nanoparticle delivery systems that could keep the drug dose from releasing into the gastrointestinal tract for at least 6 h. Two kinds of nanoparticle formations based on the so-called conjugate-by-conjugate strategy were introduced in the study. In the first conjugate-by-conjugate structured nanoparticle formation, TPGS was conjugated with an HPMC-chitosan conjugate, followed by the drug loading process. In the second approach, the drug was loaded with TPGS directly and subsequently conjugated with the HPMC-chitosan conjugate. Beneficially, polyvinyl alcohol could act not only as a stabilizing agent but also as a crosslinking agent for the nanoparticles. This study created newly modified structures of HPMC and chitosan, altering their physicochemical properties that could then retard drug release. The nanoparticles were cytotoxic towards MDA-MB-231 breast cancer cells when docetaxel was loaded in the nanoparticles, particularly the nanoparticles produced in the second approach, demonstrating their ability to kill cancerous cells and their potential for further applications in cancer therapy. Additionally, when Caco-2 cells were used as an absorption model in a transport study, the nanoparticles in the second approach showed their capacity to increase drug permeability across the monolayers of Caco-2 cells compared to the free-drug solution. This study also illustrated the enhanced uptake of the nanoparticles by the Caco-2 cells, implying enhanced absorption through the intestine. Therefore, these oral nanoparticles can be considered for delivery systems of agents that are sensitive to the gastrointestinal tract so that they can be transported across the epithelial cells to the bloodstream to deliver the loading cargo at an optimal concentration.

Most pH-sensitive polymer coating studies for potential colonic delivery systems apply multiple layers to protect the active agent from degradation and early release in the stomach and small intestine. This study designed a single-coat pH-sensitive layer for colon-specific delivery with a potential biopolymer, namely, zein. The tablets were coated with a pH-sensitive film combining zein and Kollicoat® MAE 100P. A scanning electron microscope (SEM) was used to study the surface characteristics of the coating layers, and Fourier transform infrared spectroscopy (FTIR) was used to investigate the molecular interactions between these coating materials. The delivery system showed its potential to prevent the release of drug in gastric and small intestinal simulated media for the delayed release of drug at the expected pH of the colon. The SEM pictures of the coated tablets showed the uniformity of the coating film, although there were some small pores on the surface. The FTIR spectra confirmed that no chemical interaction occurred between two coating materials. The percentage of zein in the coating solution along with the amount of coating were important factors that should be carefully considered during the preparation of the coated tablets to achieve the purpose of this study. This strategy provides a promising design that can effectively carry drugs to the targeted site and also reduce the preparation time.

The aim of this study was to investigate hydrophilic-hydrophobic conjugates as new carriers for nano-sized solid dispersions (SDs). The amphiphilic conjugates were prepared via an esterification reaction between hydroxypropyl methylcellulose (HPMC) and zein. Four formulations of conjugates were investigated with different ratios of zein to HPMC (1:5, 1:10, 1:20, and 1:40). Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy and particle size analyses were performed to characterize and optimize the formulation for SD. Isradipine and prednisolone were chosen as poorly water-soluble drugs for SD using the conjugate as a carrier. Dissolution tests, particle size analyses, powder X-ray diffraction and FTIR were conducted to determine the dissolution enhancement and its mechanism. The conjugate formed small particles as a self-assembled carrier. Although the SD with isradipine or prednisolone showed a small increase in particle size, the dissolution rate of those drugs in SD increased significantly compared to pure drugs. The interaction between the drug and conjugate was attributed to the formation of small particles and changes to the drug crystallinity. This study demonstrated that the hydrophilic-hydrophobic conjugate is a promising material for SD, with the potential of reducing drug particles to nano size in addition to promoting drug amorphousness or molecular interactions.

Although fucoidan (FU) shows potential bioactivity against various diseases, it has also been demonstrated to be an excellent material for nanodelivery. FU can be utilized to prepare nanoparticles for drug loading or to stabilize nanoparticles and is often incorporated into nanostructure materials to extend or maximize its role in theranostics applications. This review discusses strategies involving FU and other material combinations used as nanostructures for biomedical applications with a focus on chitosan-FU mixtures for oral delivery and FU-based surface functionalization for targeting and theranostics. The ability of FU to form different nanostructures is also reviewed. Moreover, various types and mechanisms of combinations involving FU-based nanostructures are discussed. A discussion of the current outlook and future studies provides ideas for more efficacious methods for FU-based nanoparticles and could enable their utilization in clinical trials.

Solubilizing adjuvants are commonly used to dissolve insoluble drugs by simply adding in a formulation. In this study, gelatin and oleic acid sodium salt (OAS), a generally recognized as safe-listed material were chosen and conjugated to develop a natural solubilizing adjuvant using the fattigation platform technology to enhance solubility and dissolution rate of poorly water-soluble drugs according to self-assembly and nanonization principle when simply mixed with poorly water-soluble drugs. We synthesized the gelatin and OAS conjugates (GOC) at three different ratios (1:1, 1:3, 1:5; GOC 1, GOC 2, and GOC 3, respectively) via the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction using a spray dryer. This amphiphilic micronized GOC was self-assembled into nanoparticles. The synthesis of new amphiphilic conjugates was identified through Fourier transform-infrared (FT-IR) spectroscopy. The powder properties of the GOCs, such as angle of repose, bulk density, and tapped density were varied with the oleic acid bonding ratio. Then, GOCs were utilized to investigate the enhanced solubility and release rate of various poorly water-soluble drugs such as cilostazol (CSZ), coenzyme Q10, ticagrelor, telmisartan, aprepitant and itraconazole as model drugs. Based on the solubility studies by concentration and type of GOCs, 3% GOC 2 was selected. When this GOC was mixed with these model drugs by the physical mixing, wetting and hot melting methoods, the solubility was highly enhanced compared to the pure control drug, ranging from 20 to 150,000 times. In case of CSZ, all formulations were significantly improved release rate compared to the of CSZ alone and the reference tablet, cilostan® (Korea United Pharm) in simulated intestinal fluid containing 0.2% sodium lauryl sulfate. Differential scanning calorimetry and powder X-ray diffraction were conducted to confirm the crystal polymorphic structure of CSZ, and as a result they changed to diminutive peak intensity compared to CSZ alone. Field-emission scanning electron microscopy indicated that GOC was round with a reduced size of about 100 nm. The reduction of drug particles via nanonization and self-assembly of amphiphilic GOC in an aqueous media could be a key factor to improve poor water solubility by providing a favorable dispersion of drug molecules in an amphiphilic network.

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.

The improvement of mucoadhesive buccal formulations has attracted profound interest in recent years. Drug permeability and controlled drug release via this route of administration are still a concern for effective therapy, although various strategies have been proposed. Advanced developments in nanotechnology have been investigated with promising clinical applications. The incorporation of nanoparticles in dosage forms for buccal delivery not only ensures efficient delivery but also reduces side effects to biological systems. Many approaches have been suggested to load and deliver nanoparticles containing drugs to the buccal mucosa both in topical and systemic administrations. This paper describes recent advanced concepts to include nanoparticles in dosage forms with improving drug delivery or targeting. The classification and discussion of these technologies are aimed at providing an overview of current strategies for applying controlled drug delivery. All remarkable findings will encourage innovative nanoparticle-delivered dosage forms for buccal delivery in clinical applications.

In recent years, various oral dosage forms using biomaterials have been developed to deliver drugs to the colon for therapy due to the advantages of local treatment and its ideal location for drug delivery. To achieve site-specific delivery, the complete drug should be released in the colon, while the drug must be protected or their delivery minimized in the stomach and small intestine. The use of natural or synthetic polymers has been reported for these purposes. The roles of zein in drug delivery have been identified with various types of formulations for improving bioavailability, controlled drug release and targeted delivery. Although zein has been demonstrated as a potential material for pharmaceutical applications, a review of zein in the gastrointestinal tract for stabilizing drug- and colon-specific delivery is still missing. In the present review, we aim to provide typical strategies for using zein in formulations to minimize drug release/ensure drug protection in the upper part of the gastrointestinal tract. Furthermore, effective fabrications or modifications for drug release in the colon will be highlighted. This primary resource of related methods of using zein in the gastrointestinal tract will advance technologies for using it as a natural polymer for drug delivery.

Despite several studies on film-forming systems with the advantages of both the film and the hydrogel, there are still no effective systems for fast film formation with a high level of control over permeability. In this study, a film-forming system for the delivery of nanomedicine, termed a film-forming nanogel (FFN), was produced and investigated for the first time to meet this need. The objective of this research was to study a new generation of film-forming hydrogels (FFHs) loaded with curcumin nanoparticles (CUR-GNPs) for transdermal applications. FFHs were prepared by employing zein and HPMC 4000 as film-forming polymers. Meanwhile, CUR-GNPs were obtained by sonoprecipitation. The film-forming time, particle characteristics and FFN drug release profile were assessed. The optimized FFH had a smooth surface and a fast drying time of 6 min and 4.5 min in vitro and ex vivo, respectively. Additionally, high, sustained drug permeation from the FFN was observed after 24 h. The FFH containing CUR-GNPs showed potential for application in transdermal drug delivery with a fast film-forming time, uniform particle dispersion and high, sustained drug permeation.

Nanoconjugations have been demonstrated to be a dominant strategy for drug delivery and biomedical applications. In this review, we intend to describe several strategies for drug formulation, especially to improve the bioavailability of poorly water-soluble molecules for future application in the therapy of numerous diseases. The context of current studies will give readers an overview of the conjugation strategies for fabricating nanoparticles, which have expanded from conjugated materials to the surface conjugation of nanovehicles. Moreover, nanoconjugates for theranostics are also discussed and highlighted. Overall, these state-of-the-art conjugation methods and these techniques and applications for nanoparticulate systems of poorly water-soluble drugs will inspire scientists to explore and discover more productive techniques and methodologies for drug development.

Despite many available approaches for transdermal drug delivery, patient compliance and drug targeting at the desired concentration are still concerns for effective therapies. Precise and efficient film-forming systems provide great potential for controlling drug delivery through the skin with the combined advantages of films and hydrogels. The associated disadvantages of both systems (films and hydrogels) will be overcome in film-forming systems. Different strategies have been designed to control drug release through the skin, including changes to film-forming polymers, plasticizers, additives or even model drugs in formulations. In the current review, we aim to discuss the recent advances in film-forming systems to provide the principles and review the methods of these systems as applied to controlled drug release. Advances in the design of film-forming systems open a new generation of these systems.

Background More than 60% of the active pharmaceutical ingredients, which are classified as Biopharmaceutics Classification System class II. The limited solubility of these drug may lead to low therapeutic effects. Methods Nanoprecipitation presents some advantages because it is a straightforward method with low-cost equipment that is easy to scale up. Results However, there are two technical issues of concern related to this method. First, the two solvents used for this approach must be miscible; concomitantly, the drug has to be soluble enough in a solvent but not in the antisolvent. Second, the particle growth needs to be adjusted by surfactant addition. Conclusion In this review, nanoprecipitation methods and solvent removal techniques for poorly water soluble drugs will be discussed.

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

The aim was to design a pH-sensitive pulsatile drug delivery system that allows for an on-off pulsed release of a drug using polyacrylic acid (PAA) blended with ethyl cellulose (EC) in different ratios. PAA, a polyelectrolyte polymer, exhibits a highly coiled conformation at low pH but a highly extended structure at high pH. Fumaric acid, which is an internal acidifying agent, was incorporated into the hydroxypropyl methylcellulose-based core tablets to create an acidic microenvironmental pH (pH(M)). The concentration of fumaric acid inside the core tablet and the ratio of PAA/EC in the coating layer were very crucial in modulating drug release behaviors. When the fumaric acid was retained in the core tablet, it gave a more acidic pH(M), so that the PAA was kept in a highly coiled state in the coated film, which hindered drug release ("off" release pattern). Interestingly, the release profiles of the drug and fumaric acid from coated tablets showed the on-off pulsed pattern upon dissolution. Imaging analyses using scanning electron microscopy, near-infrared imaging, confocal laser scanning microscopy, and Fourier transform infrared spectroscopy confirmed this on-off release behavior of the drug and fumaric acid from coated tablets.