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Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age‐appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children‐centric formulation design for new chemical entities, or to repurpose/reformulate off‐patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age‐appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product. [ABSTRACT FROM AUTHOR]

Paper‐based electronics are emerging as a new class of technology with broad areas of application. Despite several efforts to fabricate new types of flexible electronic devices by screen printing of conductive paste, many of them are often nonbiodegradable, toxic, and expensive, limiting their practical use in bioresorbable paper‐based electronics. To address this need, a highly conductive and biodegradable bimodal conductive paste is developed using cost‐effective zinc‐based micro and nanoparticles with a facile low‐temperature sintering process compatible with paper substrates. The two‐step sintering process involves the removal of the insulating zinc oxide layer by spray coating acetic acid followed by a heat press sintering process to ensure the formation of highly packed and continuous metallic traces. The required conditions for the heat press sintering process are systematically studied using electrical, optical, and mechanical characterization techniques. The results of these investigations revealed an ultra‐packed microstructure with high electrical conductivity (0.5 × 105 S m−1) and low oxide content that is obtained with a heat press sintering setting of 220 °C for 60 s. Finally, as a proof of concept, the conductive paste with an optimized sintering process is used to fabricate a wearable wireless heater for remote‐controlled release of therapeutics. The controlled delivery of the system is validated in the practical and on‐demand delivery of antibiotics for eradicating commonly found bacteria such as Staphylococcus aureus in dermal wound infections. The biocompatibility of all the materials and manufacturing process is validated by NIH/3T3 fibroblast cells via MTT assay and live/dead staining. [ABSTRACT FROM AUTHOR]

Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease‐related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice. [ABSTRACT FROM AUTHOR]

Recently, neurological disorders have led to a growing global burden of fatalities and disabilities. The limited capacity for natural self‐regeneration poses a significant challenge in repairing nervous system injuries, which is closely related to the complex microenvironment and nonregenerative nature of neurons. Metal–organic frameworks (MOFs), with their distinctive structure and properties including high surface area, porosity, tunability, stimuli‐responsive behavior, biocompatibility, and biodegradability, stand as an auspicious platform for devising therapeutic strategies aiming at nerve regeneration and repair. By taking advantage of these characteristics, researchers have the opportunity to explore innovative methods including endogenous stimulation, magnetic response therapy, phototherapy, ultrasound therapy, and drug delivery systems for the treatment of neurological diseases. Moreover, MOFs‐based stem cell therapy also is developed to inhibit neuroinflammation and oxidative stress, promote axon growth, regulate stem cell differentiation, promote nerve regeneration, and finally restore the function of injured nerves. In this paper, the preparation strategy and biological characteristics of MOFs, highlighting their applications in repairing nerve injuries and treating neural stem cells is presented. Finally, an outlook on the future development and challenges in the field of neuroscience concerning MOFs is provided. [ABSTRACT FROM AUTHOR]

Noise‐induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is a potential therapeutic strategy. In this paper, a novel natural biomaterials‐derived multifunctional delivery system using silk fibroin‐polydopamine (PDA)‐composited inverse opal microcarriers (PDA@SFMCs) is presented for inner ear drug delivery and NIHL therapy. Due to their large specific surface area and interpenetrating nanochannels, PDA@SFMCs can rapidly load active biomolecules making them a convenient medium for the storage and delivery of such molecules. In addition, surface modification of PDA enables the microcarriers to remain in the round window niche, thus facilitating the precise local and directed delivery of loaded drugs. Based on these features, it is demonstrated here that n‐acetylcysteine‐loaded silk microcarriers have satisfactory antioxidant properties on cells and can successfully prevent NIHL in guinea pigs. These results indicate that the natural multifunctional silk microcarriers are promising agents for local inner ear drug delivery in the clinic. [ABSTRACT FROM AUTHOR]

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier‐based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency. [ABSTRACT FROM AUTHOR]

Metal nanoparticles having magnetic properties are exciting for application in the directed transport of anticancer drugs encapsulated in them. To ensure drug‐loading capacity and controlled release, surface modification with host molecules is a fascinating choice. In this paper, we report the synthesis and surface modification of magnetic cobalt metal nanoparticles with oligosaccharide host molecules (β‐cyclodextrin) tethered on the surface. A β‐cyclodextrin‐folate derivative is synthesized and characterized using Infrared‐, Nuclear Magnetic Resonance‐, and Matrix‐Assisted Laser Deposition Ionization‐Time of Flight mass spectrometry. The size of the cobalt nanoparticles carrying the host molecule on the surface is ~10 nm. The nanoparticles are characterized using X‐Ray Diffraction, Transmission Electron Microscopy, particle size analyzer, Energy‐Dispersive X‐ray, and X‐ray Photoelectron Spectroscopy. The bare magnetic nanoparticles also show a strong saturation magnetization of 142.21 emu g−1. The chemotherapeutic drug 5‐fluorouracil is loaded on the surface‐modified cobalt nanoparticles through host: guest complexation mode and its controlled release is measured in‐vitro. The slow release is spread over more than 14 days, and a complete release of the loaded therapeutic cargo is not reached. The release is pH‐dependent and changes with acidic levels of the medium. The anticancer activity of the drug‐loaded nanocarrier on MDA‐MB‐231 (breast cancer) cells is investigated. The mechanism of cell death is studied, and the cells are found inhibited in the synthesis phase. Flow cytometric analysis shows that 79.70 % of the empty nanocarrier‐treated and 74.86 % 5‐fluorouracil‐loaded nanocarrier‐treated MDA‐MB‐231 cells were in the early apoptosis phase. This new combination nanocarrier is intriguing owing to its structural and magnetic properties, and the action on cell lines. [ABSTRACT FROM AUTHOR]

This paper focuses on the development of hollow starch nanoparticles (HSNPs) as promising carriers for poorly soluble drugs. A new and efficient method is presented, based on an in situ gas‐foaming/salt‐leaching process within individual starch nanoparticles prepared by a solvent displacement technique. Characterization using dynamic light scattering, transmission electron microscopy, and nitrogen adsorption/desorption analysis confirmed the successful preparation of HSNPs. Solid dispersion systems with piroxicam (PRX) as a model drug were formulated to evaluate HSNPs' potential as poorly water‐soluble drug carriers. Solid‐state properties, dissolution behavior and stability of PRX‐HSNPs solid dispersions were investigated. In vitro dissolution studies revealed that using hydrophilic HSNPs as carriers significantly improved the release of PRX. Solid‐state characterization showed that the main reason for the improved dissolution was the adsorption of PRX on the outer and inner surfaces of the HSNPs in an amorphous state. Stability studies demonstrated that the amorphous nature of loaded PRX remained unaffected even after 12 weeks of storage at 75 % relative humidity. Accordingly, the proposed HSNPs offer a promising alternative for the delivery of poorly water‐soluble drugs. In addition, the synthesis strategy demonstrated for HSNPs is easy, efficient and could be extended to the preparation of other hollow polymeric nanoparticles. [ABSTRACT FROM AUTHOR]

Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels. [ABSTRACT FROM AUTHOR]

Biomolecule‐incorporated metal‐organic frameworks (b‐MOFs) exhibit enhanced bioavailability and biocompatibility, making them an ideal option for use as drug delivery vehicles. While b‐MOFs possess outstanding drug loading and release capabilities, their microscale crystal sizes restrict their applicability as nanocarriers and drug delivery systems. To overcome this limitation, this paper presents a microwave‐irradiation‐based technique for the synthesis of porous adenine‐incorporated Zn‐based MOFs with particle sizes of approximately 200 nm as paclitaxel nanocarriers. The nanomaterial demonstrated a substantial paclitaxel loading capacity of 637 mg g−1. Moreover, it effectively increased the solubility of paclitaxel by 2.5‐fold compared to that of the free form. Thus, the nano MOF is a promising delivery vehicle for paclitaxel. Notably, the paclitaxel‐loaded nano MOF exhibited higher toxicity toward cancer cells than the free drug, further highlighting its potential as an effective anticancer agent. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) has been widely accepted in keratocyte carcinoma and an increasing number of literatures concerning PDT in skin cancer is published. But a detailed examination of publication patterns of PDT in skin cancer has not yet been carried out. Methods: Bibliographies were retrieved from Web of Science Core Collection restricted the publication date from January 1, 1985 to December 31, 2021. The search terms were photodynamic therapy and skin cancer. Visualization analysis and statistical analysis were performed by VOSviewer (Version 1.6.13), R software (Version 4.1.2) and Scimago Graphica (Version 1.0.15). Results: 3248 documents were selected for analysis. The results showed that the number of annual publications related to PDT in skin cancer was gradually increased and would continue to increase in the future. The results illustrated that "melanoma", "nanoparticles", "drug‐delivery", "mechanism", "delivery" and "in‐vitro" are newly occurred topics. The most prolific country was the United States and the most productive institution was the University of Sao Paulo in Brazil. German researcher Szeimies RM published the most papers related to PDT in skin cancer. British Journal of Dermatology was the most popular journal in this field. Conclusion: The topic that PDT in skin cancer is a heated issue. Our study revealed the bibliometric result of the field, which might provide the prospects for further research. We recommend future investigations focusing on PDT in treating melanoma, innovation of photosensitizer, improvement of drug delivery and the mechanism of PDT in skin cancer. [ABSTRACT FROM AUTHOR]

Background: Ferritin, a ubiquitously distributed iron storage protein, can specifically target tumor cells through transferrin receptor 1. Due to its rearrangeable nanocage structure, ferritin can be loaded with anticancer drugs. Combined with amino acid modifications on the outer- and/or inner-spaces of the nanocage, ferritins can be further coupled with antigens, antibodies, and nucleotide sequences. Since ferritin is naturally presented in the human body, when used in vivo, ferritin exhibits good biocompatibility, and no immunogenic response occurs. These makes ferritin an ideal nanocarrier which shows broad application prospects in cancer therapy. Methods: In this study, to find articles, a search was made in PubMed with the keywords ferritin, drug delivery, drug delivery, and cancer treatment. Results: According to the investigation, some studies suggest that ferritin can be loaded with drugs and targeted for delivery to tumor tissue. Therefore, ferritin nanocarriers loaded with drugs can be used in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and immunotherapy. Importantly, the specific targeting of ferritin nanocarriers to tumor cells increases the effectiveness of related therapies and reduces side effects. Conclusions: We conclude in this paper that the superior properties of ferritin nanocarriers as an emerging drug delivery system make them a promising cancer treatment strategy. In the future, it is worth conducting clinical trials to further investigate the safety and efficacy of ferritin nanocarriers in patients. [ABSTRACT FROM AUTHOR]

While autoregulative adaptation is a common feature of living tissues, only a few feedback-controlled adaptive biomaterials are available so far. This paper herein reports a new polymer hydrogel platform designed to release anti-inflammatory molecules in response to the inflammatory activation of human blood. In this system, anti-inflammatory peptide drugs, targeting either the complement cascade, a complement receptor, or cyclophilin A, are conjugated to the hydrogel by a peptide sequence that is cleaved by elastase released from activated granulocytes. As a proof of concept, the adaptive drug delivery from the gel triggered by activated granulocytes and the effect of the released drug on the respective inflammatory pathways are demonstrated. Adjusting the gel functionalization degree is shown to allow for tuning the drug release profiles to effective doses within a micromolar range. Feedback-controlled delivery of covalently conjugated drugs from a hydrogel matrix is concluded to provide valuable safety features suitable to equip medical devices with highly active anti-inflammatory agents without suppressing the general immunosurveillance. [ABSTRACT FROM AUTHOR]

Hydroxyapatite/tricalcium phosphate (HA/β‐TCP) has been widely studied as a drug carrier, but the drug loading and release rate of the composites with different morphology significantly vary. In this paper, needle‐shaped, rod‐shaped, and ordered porous HA/β‐TCP composite was prepared by chemical co‐precipitation method, and ibuprofen (IBU) was used as a drug model to study the sustained‐release properties of IBU in vitro. The results showed that morphology of the HA/β‐TCP composite had a significant effect on the drug loading of IBU. The IBU loading of the ordered porous composite was as high as 101.3 mg/g, which was 2.2 times and 3.46 times higher than that of the rod‐shaped and needle‐shaped composite to IBU, respectively. The drug release test of IBU showed that the release rate of the ordered porous HA/β‐TCP to IBU was slower than that of the rod‐shaped and needle‐shaped composite in the initial 10 h, and reached the drug release equilibrium after the subsequent 30 h. The cumulative release of the ordered porous HA/β‐TCP composite to IBU reached 83.79 %, which was significantly smaller than that of the needle‐shaped and the rod‐shaped, showing better slow‐release performance for IBU. The ordered porous HA/β‐TCP composite have great application potential in quantitative drug delivery systems. [ABSTRACT FROM AUTHOR]

This paper deals with the development of polymeric nanocarriers based on amphiphilic copolymers of N‐vinyl‐2‐pyrrolidone and acrylic acid of various molecular weights synthesized through the AIBN‐initiated radical copolymerization of N‐vinyl‐2‐pyrrolidone and acrylic acid in the presence of n‐octadecyl mercaptan. The structure of the copolymers is characterized by 1Н NMR, 13С NMR, IR and MALDI‐TOF MS spectroscopy. It is shown that the length of the hydrophilic block defines the size of the nanoaggregates while impacting the steric stabilization efficiency and the probability of the interchain hydrogen bond formation. The hydrogen bonds formation between the residues of N‐vinyl‐2‐pyrrolidone and acrylic acid is in agreement with the reduction of the ζ‐potential of the nanoaggregates and the critical aggregation concentrations upon increasing the molecular weight. The presence of acrylic acid residues in the amphiphilic macromolecules leads to a higher affinity for doxorubicin and slow partial release of doxorubicin bonded with the aggregates' corona, which is helpful for reducing its cardiac toxicity. Nanoaggregates with a paclitaxel‐loaded hydrophobic core are obtained, showing the possibility of dual loading. The amphiphilic copolymers of N‐vinyl‐2‐pyrrolidone and acrylic acid containing an n‐octadecyl thio end group are thus promising candidates for combination cancer therapy with immobilized anti‐cancer drugs, paclitaxel, and doxorubicin. [ABSTRACT FROM AUTHOR]

The incidence and lethal rate of cancers are rapidly rising recently, however current treatments of cancers, such as surgical resection, radiotherapy, chemotherapy and targeted therapy, usually require long treatment period and have more side effects and high recurrence rate. Enzyme‐powered micro/nanomotors (EMNMs), with powerful self‐propulsion, enhanced permeability and good biocompatibility, have shown great potential in crossing biological barrier and targeted drug transportation for cancer treatment; moreover, advanced approaches based on EMNMs such as photothermal therapy and starvation therapy have also been widely explored in cancer treatment. Although there are several review works discussing the progress of micro/nanomotors for biomedical applications, there is not one review paper with the focus on the cancer treatment based on EMNMs. Therefore, in this review, we try to concisely and timely summarize the recent progress of cancer treatment based on enzyme‐driven micro/nanomotors, such as brain tumors, bladder cancer, breast cancer and others. Finally, the challenges and outlook of cancer therapy based on EMNMs are discussed, hoping to provide fundamental guidance for the future development. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Inspired by the adaptation of cells to the surrounding environment, the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite. The construction of endogenous membrane biomimetic nanocarriers (EMBNs) not only retains the structure of membrane surface protein, but also has the properties of nanoparticles (NPs), also provides the ability of natural interaction between nanomaterials and organisms, thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application. In this paper, the construction methods of EMBNs are reviewed, focusing on a simple method to prepare membrane proteins. Secondly, EMBNs were classified according a variety of cell membranes. Finally, the unique advantages of EMBNs in nanomedicine are introduced, including improving biocompatibility, homologous targeting ability, prolonging blood circulation time and immune escape ability. In nanomedicine, such as targeted delivery, phototherapy, immunotherapy and tumor imaging, multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs. [ABSTRACT FROM AUTHOR]

The stimuli‐responsiveness of injectable hydrogel has been drastically developed for the controlled release of drugs and has achieved encouraging curative effects in a variety of diseases including wounds, cardiovascular diseases, and tumors. The gelation, swelling, and degradation of such hydrogels respond to endogenous biochemical factors (such as pH, reactive oxygen species, glutathione, enzymes, glucose) and/or to exogenous physical stimulations (like light, magnetism, electricity, and ultrasound), thereby accurately releasing loaded drugs in response to specifically pathological status and as desired for treatment plan, and thus improving therapeutic efficacy effectively. This paper gives a detailed introduction of recent progresses in responsive injectable hydrogels and focuses on the design strategy of various stimuli‐sensitivities and their resultant alteration of gel dissociation and drug liberation behavior. Their application in disease treatment is also discussed. [ABSTRACT FROM AUTHOR]

Micromotors have opened novel avenues for drug delivery due to their capacity for self‐propelling. Attempts in this field trend towards ameliorating their functions to promote their clinical applications. In this paper, an ingenious suction‐cup‐inspired micromotor is presented with adhesive properties for drug delivery in the stomach. The micromotors are fabricated by using hydrogel replicating the structure of suction‐cup‐like microparticles, which derive from self‐assembly of colloidal crystals under rapid solvent extraction, followed by loading magnesium (Mg) in the bottom spherical surface. The Mg‐loaded micromotors can realize spontaneous movement due to the continual generation of hydrogen bubbles in gastric juice. The combination of unique suction‐cup‐like structure with excellent motion performance makes the micromotor an ideal carrier for drug delivery as they can efficiently adhere to the tissue. Moreover, benefiting from the porous structure, the hydrogel micromotors exhibit a high volume‐surface ratio, which enables efficient drug loading. It is demonstrated that the suction‐cup‐inspired micromotors can adhere efficiently to the ulcer‐region in the stomach and release drugs due to their distinctive architecture and spontaneous motion, exhibiting desirable curative effect of gastric ulcer. Thus, the suction‐cup‐inspired micromotors with adhesive properties are expected to advance the development of micromotor in clinical applications. [ABSTRACT FROM AUTHOR]

Stimulus‐sensitive drug delivery materials are of vital significance to modern therapeutic technology. In particular, glucose‐responsive hydrogels capable of biomimetic release of hypoglycemic drugs according to glucose concentrations are one of the current research hotspots. In this paper, an injectable, glucose‐induced disintegrated natural‐polysaccharide‐based hydrogel with good self‐healing ability and biocompatibility is reported. The glucose‐responsiveness of the hydrogel stems from the reversible phenylborate ester bonds. The glucose‐triggered disintegration and insulin release are demonstrated in the hydrogel in a physiological environment. The two polymers produced by the disintegration of the hydrogel have good biocompatibility and biodegradability. Therefore, the hydrogel is considered to result in the development of smart insulin delivery systems. [ABSTRACT FROM AUTHOR]

The main purpose herein is to provide an up‐to‐date review on noninvasive biomimetic, bioinspired, and bioengineered drug delivery system (DDS). Noninvasive DDS is an ever‐growing field critical for the applicability of drugs. It offers noninvasive administration routes with improved controlled, targeted, and triggered drug delivery. Noninvasive DDS employ many approaches and strategies, such as, nano‐ and microparticles, lipid‐based systems, sonophoresis, electrophoresis and iontophoresis, penetration enhancers, microneedles, and gels. The last decade seen a surge in research papers employing the paradigms of biomimicry, bioinspiration, and bioengineering. However, since the use of these terms in noninvasive DDS field is often inconsistent and unclear, some generalized perspectives are provided on the possible usage of these terms in future publications. Additionally, a critical discussion on the novelty and origins of these paradigms is provided. The advantages and disadvantages of each of the noninvasive routes and their current main limitations are summarized. The main aspects of indicated fields are discussed: The unique physiology of the related tissues, the main hurdles for mass transport, the various DDS tested, and materials selection. Finally, the basic concepts and therapeutic effects of these DDS are discussed and future venues for noninvasive biomimetic, bioinspired, and bioengineered DDS research are proposed. [ABSTRACT FROM AUTHOR]

This paper reports the use of a self‐assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l‐DOPA. Based on a two‐component combination of an l‐glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self‐healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l‐DOPA. These drug‐loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug‐loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically‐active drugs—a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood–brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3H‐labeled l‐DOPA out‐performed a simple intranasal l‐DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally‐delivered l‐DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions. [ABSTRACT FROM AUTHOR]

Liposomes are versatile three-dimensional, biomaterial- based frameworks that can spatially enclose a variety of organic and inorganic biomaterials for advanced targeted-delivery applications. Implementation of external-stimulicontrolled release of their cargo will significantly augment their wide application for liposomal drug delivery. This paper presents the synthesis of a carbohydrate-derived lipid, capable of changing its conformation depending on the presence of Zn2+: an active state in the presence of Zn2+ ions and back to an inactive state in the absence of Zn2+ or when exposed to Na2EDTA, a metal chelator with high affinity for Zn2+ ions. This is the first report of a lipid triggered by the presence of a metal chelator. Total internal reflection fluorescence microscopy and a single-liposome study showed that it indeed was possible for the lipid to be incorporated into the bilayer of stable liposomes that remained leakage-free for the fluorescent cargo of the liposomes. On addition of EDTA to the liposomes, their fluorescent cargo could be released as a result of the membrane-incorporated lipids undergoing a conformational change. [ABSTRACT FROM AUTHOR]

In this paper, graphene oxide/ magnetite (GO/Fe3O4) nanocomposite was synthesized as a carrier and MRI contrast agent. X‐ray diffraction (XRD) indicated that the crystalline structure of Fe3O4 nanoparticles and Furrier transform infrared spectroscopy (FT‐IR) provided evidence for the presence of Fe3O4 and GO in the nanocomposite. The surface morphology of the nanocomposite was studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The magnetic properties of the synthesized nanocomposite was studied by a vibrating sample magnetometer (VSM). The drug loading and encapsulation efficiency of the curcumin were 22 and 96 %, respectively. The comparison between drug release from GO/Fe3O4 in neutral and acidic pH was shown high release in neutral conditions. MTT results demonstrated that the GO/Fe3O4 nanocomposite illustrates considerable toxicity due to which cell viability decreased to lower than 50 % at 140 μg ml−1 concentration. The results showed that curcumin and curcumin loaded nanocomposite has a similar power of antioxidant activities. GO/Fe3O4 nanocomposite is a good magnetic resonance T2 contrast agent under the T2‐imaging sequences. The novelty of this study is the application of water‐dispersed GO/Fe3O4 with pH‐dependent release properties for designing a new colon drug delivery. [ABSTRACT FROM AUTHOR]

Manganese dioxide (MnO2)‐based functional nanomaterials have attracted great attention in the fields of nanoscience, biosensors, bioimaging, drug/gene delivery, and cancer therapy. Especially, all‐in‐one tumor microenvironment (TME) responsive MnO2‐based nanoagents have become a research hotspot due to their simple fabrication procedure, high specific surface area, controllable size and morphologies, easy surface modification, TME response, and oxygen generation. This review aims to provide a comprehensive overview of strategies for construction of MnO2‐based all‐in‐one nanoplatforms for cancer diagnosis and therapy. Major highlighted topics in this paper focus on the controllable fabrication of MnO2 nanobuilding blocks, tumor targeting accumulation, working mechanisms of enhancing therapeutic efficacy, and the necessary considerations for construction of all‐in‐one nanoplatform. Finally, the current challenges and future directions in this rapidly growing research field are also discussed, which will provide guidance on the future works about the clinical translation of MnO2‐based all‐in‐one nanoplatform. [ABSTRACT FROM AUTHOR]

Starch is a natural, renewable, and biodegradable polymer produced by many plants as a source of stored energy. The structural and functional diversity of starches makes them suitable for different applications. Various physical, chemical, and enzymatic modifications can change and improve functional properties of starch to facilitate its use for different pharmaceutical purposes. Currently, some types of starches—for example, native starch, sodium starch glycolate (chemically modified starch), and pregelatinized starch (physically modified starch)—are approved by the United States Food and Drug Administration (FDA) for use either as an isolated excipient or as a matrix for drug delivery systems in granules, capsules, tablets, suppositories, implants, stents, transdermal, and ophthalmic systems. However, the increasing number of drug moieties with varying physicochemical and stability properties along with the development of new drug production processes and drug delivery systems exert pressure on formulators to search for new excipients that achieve the desired set of functionalities. This paper offers a clear overview of native and modified starches and their use in pharmaceutical and biomedical applications, either as excipients or as drug delivery systems. In addition, some drug release mechanisms, which include encapsulants, micro/nanoparticles hydrogels and scaffolds, are discussed. [ABSTRACT FROM AUTHOR]

Hydroxyapatite(HA) are widely used in the field of drug delivery, especially nano‐HA and porous HA. However, there are few reports on the use of inverse opal HA as drug carrier. In this paper, based on the colloidal crystal template prepared by polystyrene microsphere with the diameter of 380 ± 10 nm, inverse opal HA was prepared by template method as the drug sustained‐release carrier using different dispersants and ratio of template to precursor. The results indicated that when the ratio of template to precursor was 1 : 15 and the dispersant was a mixture of water and alcohol, the prepared inverse opal HA showed a complete ordered porous morphology with uniform pore spacing. In the drug delivery test of amoxicillin, drug loading and release properties of the inverse opal HA were significantly better than that of nano‐HA. Drug loading of the inverse opal HA was about 2.17 times than that of nano‐HA, and drug‐loading performance was also obviously improved. At the same time, sustained release ability of the inverse opal HA was better than that of nano‐HA when releasing amoxicillin. In the first 3 h, the cumulative release rate of amoxicillin in the inverse opal HA was less than 40%, much lower than about 60% of nano‐HA, significantly slowing down the drug release rate and showing good persistence. Therefore, the inverse opal HA as a drug carrier could also improve the sudden release effect of drugs and make the release rate of drugs gentler. [ABSTRACT FROM AUTHOR]

Intravaginal rings (IVRs) are an established option for continuous administration of drugs in women. The combination of anastrozole (ATZ) and levonorgestrel (LNG) in an IVR with an intended 4‐week wearing period has been considered for long‐term treatment of endometriosis‐associated pelvic pain. A randomized, parallel‐group, multicenter phase 2b study to assess the efficacy and safety of different dose combinations in women with symptomatic endometriosis has recently been performed. This paper will focus on the investigation of pharmacokinetic (PK) effects of ATZ on LNG using data collected from this study. Two hundred sixteen patients were randomized to the treatment group with IVRs releasing LNG 40 μg/day alone or in combination with ATZ 300 μg/day, 600 μg/day, or 1050 μg/day for 12 weeks. PK blood samples were taken before dosing and before IVR replacement or removal (days 28, 56, and 84). The primary PK parameter was the plasma concentration in apparent steady state of ATZ and LNG at the end of each IVR wearing period. Results of PK analysis demonstrate that ATZ concentrations increased proportionally with increasing dose (geometric mean values of 7.85, 15.48, and 22.61 μg/L at 300, 600, and 1050 μg/day nominal release, respectively). All point estimates for LNG concentration in apparent steady state ratios between the mono and combination IVR groups were close to 1, and the 90% confidence interval limits were in the 0.80 to 1.25 range (1.01 [0.85‐1.19], 1.03 [0.88‐1.20], 0.94 [0.80‐1.10]). In conclusion, our data indicate there is no evidence of drug‐drug interaction of ATZ on LNG. [ABSTRACT FROM AUTHOR]

Despite the fact that progress has been made in the application of supramolecular prodrug self‐assemblies to enhance the functionality of drug‐delivery systems, corresponding research on multi‐responsive supramolecular prodrug self‐assemblies for programmed drug delivery is still limited. In this paper, the synthesis and self‐assembly behavior of supramolecular prodrug complexes (SPCs) with β‐cyclodextrin–acylhydrazone–doxorubicin (β‐CD‐hydrazone‐DOX) and the targeting of azobenzene‐terminated poly[2‐(dimethylamino)ethyl methacrylate] (Azo‐PDMA‐FA) as a building block were investigated. The obtained SPCs could also form self‐assemblies on the basis of their amphiphilic nature. Next, SPC‐based multi‐compartment vesicles and complex micelles, which were confirmed by transmission electron microscopy and dynamic/static light scattering, were obtained with good reversibility under alternative visible light or UV irradiation. Furthermore, three‐stage programmed drug‐delivery behavior was observed from dual‐responsive SPC‐based self‐assemblies by utilizing UV and pH stimuli. Specifically, the SPCs first self‐assembled into multicompartmental vesicles, which was accompanied by a slow release of DOX. Next, UV‐light irradiation induced the dissociation of β‐CD/Azo, which led to morphology transition and a slight increase in the rate of release of DOX. Upon transferring the self‐assemblies to phosphate‐buffer solution (pH 5.0), the release rates increased notably as a result of the broken acylhydrazone bond. Finally, basic cell experiments further demonstrated that the SPC‐based self‐assemblies could be internalized into cancer cells, which suggests their promise for applications in cancer therapy. Special delivery: The synthesis and self‐assembly behavior of supramolecular prodrug complexes (SPCs) with β‐cyclodextrin–acylhydrazone–doxorubicin and the targeting of azobenzene‐terminated poly[2‐(dimethylamino)ethyl methacrylate] as a building block are investigated and described. Furthermore, three‐stage programmed drug‐delivery behavior is observed from dual‐responsive SPC‐based self‐assemblies by utilizing UV and pH stimuli. [ABSTRACT FROM AUTHOR]

Abstract: Acoustically‐responsive microbubbles have been widely researched as agents for both diagnostic and therapeutic applications of ultrasound. There has also been considerable interest in magnetically‐functionalised microbubbles as multi‐modality imaging agents and carriers for targeted drug delivery. In this paper, we present a design for an integrated device capable of generating co‐aligned magnetic and acoustic fields in order to accumulate microbubbles at a specific location and to activate them acoustically. For this proof‐of‐concept study, the device was designed to concentrate microbubbles at a distance of 10 mm from the probe's surface, commensurate with relevant tissue depths in preclinical small animal models. Previous studies have indicated that both microbubble concentration and duration of cavitation activity are positively correlated with therapeutic effect. The utility of the device was assessed in vitro tests in a tissue‐mimicking phantom containing a single vessel (1.2 mm diameter). At a peak fluid velocity of 4.2 mm s−1 microbubble accumulation was observed under B‐mode ultrasound imaging and the corresponding cavitation activity was sustained for a period more than 4 times longer than that achieved with an identical acoustic field but in the absence of a magnet. The feasibility of developing a larger scale device for human applications is discussed. [ABSTRACT FROM AUTHOR]

Abstract: Self‐nanoemulsifying drug delivery system (SNEDDS) is recently studied for enhancing the bioavailability of hydrophobic drugs, such as resveratrol (RSV). However, the functional design of SNEDDS for the drug structural protection is not studied yet. Here, this paper presents an efficient approach by adding lignin (a kind of abundant biomass resource) to enhance the stability of trans‐RSV and meantime improve its oral bioavailability. Higher stability of trans‐RSV (just decreased 2% to cis‐RSV after 1 h under direct sunlight) is observed after loaded by lignin‐containing SNEDDS (RSV/SLS SNEDDS). Low toxicity, high transfer efficiency (apparent permeability coefficient >1 × 10−7 cm s−1), and bioavailability (1.371%) of RSV/SLS SNEDDS is successfully demonstrated in Caco‐2 cells and rat model, respectively. This study serves to illustrate a simple, versatile, environmental, and economic sustainability approach to the development of nanodelivery systems for light instability drugs. [ABSTRACT FROM AUTHOR]

Thin films, which are able to deliver antibiotics in a controlled way, are considered as a promising approach to combat bacterial infections. A novel drug delivery method based on reservoir/diffusion barrier is introduced in this paper. As reservoir serves a film of sputtered nylon 6,6 impregnated with ampicillin, which is then covered by a diffusion barrier from the same material. It is demonstrated that the impregnation process does not affect either the morphology or the surface chemical structure. The amount of immobilized antibiotics can be tailored by changing the reservoir film thickness, while the release kinetics can be controlled by the thickness of the diffusion barrier. Finally, it is shown that the ampicillin impregnated films have an antibacterial effect against Staphylococcus epidermidis. [ABSTRACT FROM AUTHOR]

The long-standing debate that polyphenol secondary metabolites from dietary plants are important nutritional components continues due to compelling evidence for their abilities to ameliorate degenerative conditions including, cancer, neurological disorders and cardiovascular disease. The clinical use of polyphenols is not, however, mainstream as issues regarding poor selectivity, dosage, toxicity and delivery methods are unresolved. The paper by Rieder et al. suggests that the lack of selectivity, at least for the stilbene, resveratrol, may not be a major limiting factor. The present commentary is a critique of this significant finding that is focused on deciding how the use of resveratrol as clinical medicine could be advanced, and how this new information integrates with current knowledge of polyphenol physiological effects. This commentary suggests that the multi-target nature of polyphenols may be translated into reliable therapy using the current systems/network pharmacology approach concerned with developing viable therapeutic agents that achieve specific effects through interactions with a wide array of targets. Linked Article This article is a commentary on Rieder et al., pp. 1244-1258 of BJP 167:6. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.02063.x [ABSTRACT FROM AUTHOR]

A mathematical model to simulate drug delivery from a viscoelastic erodible matrix is presented in this paper. The drug is initially distributed in the matrix that is in contact with water. The entrance of water in the material changes the molecular weight, and bulk erosion can be developed depending on how fast this entrance is and how fast degradation occurs. The viscoelastic properties of the matrix also change in the presence of water as the molecular weight changes. The model is represented by a system of quasi-linear partial differential equations that take into account different phenomena: the uptake of water, the decreasing of the molecular weight, the viscoelastic behavior, the dissolution of the solid drug, and the delivery of the dissolved drug. Numerical simulations illustrating the behavior of the model are included. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This paper describes a mixture of fatty acids that is available for temperature-controlled release of drugs. The mixture consists of two fatty acids with different melting points. At a specific composition, the mixture represents a single melting point of 38-40 °C which is slightly above the normal human body temperature. To demonstrate its use in the temperature-regulated release, this study fabricates fatty acid-incorporated polymer fibers containing dye-loaded polymer particles in their core. Below the melting point of the mixture, it will be in a solid state to restrict the passing of dye loaded in the core whereas the dye can be released instantly through the generated pores at a temperature slightly higher than the melting point. The release profiles of the dye can be further manipulated by varying the amount of the mixture contained in the fibers and the composition of the mixture. [ABSTRACT FROM AUTHOR]

The presented article discusses recent advances in biomedical applications of classical magnetohydrodynamics (MHD), with a focus on operating principles and associated material considerations. These applications address novel approaches to common biomedical problems from microparticle sorting for lab-on-a-chip devices to advanced physiological monitoring techniques. 100 papers in the field of MHDs are reviewed with a focus on studies with direct biomedical applications. The body of literature is categorized into three primary areas of research including material considerations for MHD applications, MHD actuation devices, and MHD sensing techniques. The state of the art in the field is examined and research topics are connected to provide a wide view of the field of biomedical MHDs. As this field develops, the need for advanced simulation and material design will continue to increase in importance in order to further expand its reach to maturity. As the field of biomedical MHDs continues to grow, advances toward microscale transitions will continue to be made, maintaining its clinically driven nature and moving toward real-world applications. [ABSTRACT FROM AUTHOR]

Purpose: Multileaf collimator (MLC) tracking can be used for motion management. However, on account of mechanical constraints, it is a crucial challenge for conventional MLCs (3-4 cm/s in leaf speed) to track fast targets, especially moving in 2D in the beam's eye view (BEV). Our group has recently developed a "high-speed" MLC (HS-MLC) prototype with a maximum leaf speed of 40 cm/s, which makes it possible to track the vast majority of moving targets without violation of mechanical constraints. The major innovation of the HS-MLC design is that it employs linear motors instead of rotary motors to drive leaves. This paper mainly aims to evaluate the performance of the HS-MLC in real-time intensity-modulated radiation therapy delivery to targets moving in 2D in the BEV. Methods: A 2D real-time tracking algorithm was proposed first based on a previous superimposing leaf sequencing method. Then, simulations were performed to evaluate the delivery performance including fluence accuracy, efficiency, delivery time, and number of monitor units under various settings of limiting coefficient and dose rate for four clinical fluence maps and two target speeds. The comparisons between the HS-MLC with a "medium-speed" MLC (MS-MLC, 10 cm/s) and a "low-speed" MLC (LS-MLC, 5 cm/s) were also made. For validation, experiments were carried out on the HS-MLC prototype in the lab environment. A camera-based measurement system was set up to detect actual leaf trajectories. Results: Simulation results indicate that a limiting coefficient of 0.5 and a dose rate of 400 MU/min are "optimal" in the sense of getting best compromise between delivery time and number of monitor units. Under the optimal parameters, the HS-MLC achieved 100% in efficiency, 18.1 s in delivery time, and 121.2 MU in number of monitor units on average for the "fast" target speed, compared to 94%, 20.6 s, and 129.9 MU with the MS-MLC, and to 53%, 40.2 s, and 141.1 MU with the LS-MLC. The benefits of increased leaf speed were demonstrated. The experimental results agreed with the simulation ones, which further confirmed the efficacy of the HS-MLC. Conclusions: The HS-MLC is superior to conventional MLCs when used for tracking, benefiting from its high leaf speed. These results indicate that the novel HS-MLC is feasible for high-accuracy and high-efficiency motion management. It also offers guidance for future MLC design. [ABSTRACT FROM AUTHOR]

One major focus of antitumor drug delivery is the development of suitable carriers for therapeutic molecules. Superparamagnetic iron oxide nanoparticles are promising magnetic drug carriers as they are biocompatible, biodegradable, readily tunable, superparamagnetic, and, thus, controllable by an external magnetic field. In this paper, we propose and demonstrate a bioinspired synthesis of polydopamine-functionalized superparamagnetic magnetite nanocrystal clusters for antitumor drug delivery. Firstly, an oil-phase evaporation-induced self-assembly strategy was introduced to fabricate magnetite nanocrystal clusters (MNCs), which have the advantage of increased magnetization through a synergistic effect. Secondly, the surface functionalization of the MNCs with polydopamine (PDOPA) was demonstrated. Thirdly, the antitumor drug epirubicin (EPB) was attached to the surface of MNC@PDOPA, and its applicability for use as a magnetically guided carrier for antitumor drug delivery was demonstrated. The achieved MNC@PDOPA exhibits superparamagnetic characteristics, improved magnetization behavior under an external magnetic field, well-controlled loading, and pH-responsive properties; therefore, the MNC@PDOPA is a promising nanomaterial for in vivo EPB delivery applications and tumor chemotherapy. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is increasingly considered as an effective imaging method to support several stages of radiation therapy. The combined usage of functional and morphological imaging in state-of-the-art PET/CT scanners is rapidly emerging to support the treatment planning process in terms of improved tumor delineation, and to assess the tumor response in follow-up investigations after or even during the course of fractionated therapy. Moreover, active research is being pursued on new tracers capable of providing different insights into tumor function, in order to identify areas of the planning volume which may require additional dosage for improved probability of tumor control. In this respect, major progresses in the next years will likely concern the development and clinical investigation of novel tracers and image processing techniques for reliable thresholding and segmentation, of treatment planning and beam delivery approaches integrating the PET imaging information, as well as improved multimodal clinical instrumentation such as PET/MR. But especially in the rapidly emerging case of ion beam therapy, the usage of PET is not only limited to the imaging of external tracers injected to the patient. In fact, a minor amount of positron emitters is formed in nuclear fragmentation reactions between the impinging ions and the tissue, bearing useful information for confirmation of the delivered treatment during or after therapeutic irradiation. Different implementations of unconventional PET imaging for therapy monitoring are currently being investigated clinically, and major ongoing research aims at new dedicated detector technologies and at challenging applications such as real-time imaging and time-resolved in vivo verification of motion compensated beam delivery. This paper provides an overview of the different areas of application of PET in radiation oncology and discusses the most promising perspectives in the years to come for radiation therapy planning, delivery, and monitoring. [ABSTRACT FROM AUTHOR]

Microparticles (MPs) have great potentiality in material science- based applications. Their use in biology is however limited to clinics and has rarely been exploited in the pharmaceutical context. Unlike nanoparticles (NPs), they are amenable to routine detection by flow cytometry and confocal microscopy. Though MPs can constitute a wide variety of materials, including ceramics, glass, polymers, and metals and can be synthesized by chemical process but wet processes for the preparation of microparticles have rarely been attemped. In this paper, a thrombotic route is shown to successfully generate biocompatible MP of a model anticancer drug (doxorubicin hydrochloride). Synthesis of MPs from platelets and drug loading in to these MPs was confirmed by flow cytometry and confocal microscopy. Human cervical cancer cell line (HeLa) was treated with these drug-loaded MPs to investigate whether the loaded MPs have the capacity to deliver drug to the cancer cells. In addition, Magnetic force microscopy was used to detect the preparation of MPs loaded with magnetic NPs. The efficiency of the drug-loaded MPs in inducing cytotoxicity in cancer cell line, shown to be significantly higher than the free drug itself. The drugloaded MP is shown to have a much higher cytotoxic propensity than the free drug applied at comparable doses. The thrombotic approach can also be applied to synthesize MP containing NPs which in turn can lead to generate a wide variety of new biocompatible materials. [ABSTRACT FROM AUTHOR]

Purpose: Several authors have recommended a 2 mm tolerance for multileaf collimator (MLC) positioning in sliding window treatments. In volumetric modulated arc therapy (VMAT) treatments, however, the optimal tolerance for MLC positioning remains unknown. In this paper, the authors present the results of a multicenter study to determine the optimal tolerance for both techniques. Methods: The procedure used is based on dynalog file analysis. The study was carried out using seven Varian linear accelerators from five different centers. Dynalogs were collected from over 100?000 clinical treatments and in-house software was used to compute the number of tolerance faults as a function of the user-defined tolerance. Thus, the optimal value for this tolerance, defined as the lowest achievable value, was investigated. Results: Dynalog files accurately predict the number of tolerance faults as a function of the tolerance value, especially for low fault incidences. All MLCs behaved similarly and the Millennium120 and the HD120 models yielded comparable results. In sliding window techniques, the number of beams with an incidence of hold-offs >1% rapidly decreases for a tolerance of 1.5 mm. In VMAT techniques, the number of tolerance faults sharply drops for tolerances around 2 mm. For a tolerance of 2.5 mm, less than 0.1% of the VMAT arcs presented tolerance faults. Conclusions: Dynalog analysis provides a feasible method for investigating the optimal tolerance for MLC positioning in dynamic fields. In sliding window treatments, the tolerance of 2 mm was found to be adequate, although it can be reduced to 1.5 mm. In VMAT treatments, the typically used 5 mm tolerance is excessively high. Instead, a tolerance of 2.5 mm is recommended. [ABSTRACT FROM AUTHOR]

Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, we propose a simple computational framework for the rapid simulation of the delivery of substances into cells. Our approach treats the substances and the cell membrane as a collection of particles forming a discrete dynamical system, which is described by Newtonian equations in a purely mechanistic way. Detailed aspects about the modeling of particle interactions are discussed and resolved. The main advantage of such an approach is that it can offer a good qualitative picture of the delivery mechanism without the need to resort to detailed descriptions of the complex intermolecular interactions that are observed at small scales of the cell membrane. A numerical time integration scheme is formulated for solution of the system dynamics, and examples of simulations are provided. Computational particle-based models render reliable and fast simulation tools. We believe they can be very useful to help advance the design of delivery systems. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: In the absence of a collimation system the lateral penumbra of spot scanning (SS) dose distributions delivered by low energy proton beams is highly dependent on the spot size. For current commercial equipment, spot size increases with decreasing proton energy thereby reducing the benefit of the SS technique. This paper presents a dynamic collimation system (DCS) for sharpening the lateral penumbra of proton therapy dose distributions delivered by SS. Methods: The collimation system presented here exploits the property that a proton pencil beam used for SS requires collimation only when it is near the target edge, enabling the use of trimmers that are in motion at times when the pencil beam is away from the target edge. The device consists of two pairs of parallel nickel trimmer blades of 2 cm thickness and dimensions of 2 cm x 18 cm in the beam's eye view. The two pairs of trimmer blades are rotated 90° relative to each other to form a rectangular shape. Each trimmer blade is capable of rapid motion in the direction perpendicular to the central beam axis by means of a linear motor, with maximum velocity and acceleration of 2.5 m/s and 19.6 m/s2, respectively. The blades travel on curved tracks to match the divergence of the proton source. An algorithm for selecting blade positions is developed to minimize the dose delivered outside of the target, and treatment plans are created both with and without the DCS Results: The snout of the DCS has outer dimensions of 22.6 × 22.6 cm² and is capable of delivering a minimum treatment field size of 15 × 15 cm². Using currently available components, the constructed system would weigh less than 20 kg. For irregularly shaped fields, the use of the DCS reduces the mean dose outside of a 2D target of 46.6 cm² by approximately 40% as compared to an identical plan without collimation. The use of the DCS increased treatment time by 1-3 s per energy layer. Conclusions: The spread of the lateral penumbra of low-energy SS proton treatments may be greatly reduced with the use of this system at the cost of only a small penalty in delivery time. [ABSTRACT FROM AUTHOR]

This paper describes a method for fabricating protein-based capsules with semipermeable and enzyme-degradable surface barriers. It involves the use of a simple fluidic device to generate water-in-oil emulsion droplets, followed by cross-linking of proteins at the water-oil interface to generate a semipermeable surface barrier. The capsules can be readily fabricated with uniform and controllable sizes and, more importantly, show selective permeability toward molecules with different molecular weights: small molecules like fluorescein sodium salt can freely diffuse through the surface barrier while macromolecules such as proteins can not. The proteins, however, can be released by digesting the surface barrier with an enzyme such as pepsin. Taken together, the capsules hold great potential for applications in controlled release, in particular, for the delivery of protein drugs. [ABSTRACT FROM AUTHOR]

Hollow-structured nanomaterials with fluorescent properties are extremely attractive for image-guided cancer therapy. In this paper, sub-100 nm and hydrophilic NaYF4 upconversion (UC) hollow nanospheres (HNSs) with multicolor UC luminescence and drug-delivery properties were successfully prepared by a facile one-pot template-free hydrothermal route using polyetherimide (PEI) polymer as the stabilizing agent. XRD, SEM, TEM, and N2-adsorption/desorption were used to characterize the as-obtained products. The growth mechanism of the HNSs has been systematically investigated on the basis of the Ostwald ripening. Under 980 nm excitation, UC emissions of HNSs can be tuned by a simple change of the concentration or combination of various upconverters. As a result, the PEI-coated HNSs could be used as efficient probes for in vitro upconversion luminescence (UCL) cell imaging. Furthermore, a doxorubicin storage/release behavior and cancer-cell-killing ability investigation reveal that the product has the potential to be a drug carrier for cancer therapy. [ABSTRACT FROM AUTHOR]

This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water-soluble doxorubicin (DOX) and water-insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug-loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome-forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes. [ABSTRACT FROM AUTHOR]

Microgels are hydrogel particles ∼0.1-10 microns in size which have been increasingly explored for biomaterials applications. They can be designed to sequester drugs based on both hydrophobic and electrostatic interactions, and different strategies exist to trigger drug release from them. Microgels based on poly(ethylene glycol) are particularly attractive because of their intrinsic antifouling properties, the flexibility they bring to microgel design and synthesis, and the regulatory precedents set by PEG's use in a number of FDA-approved applications. This paper briefly reviews progress in the field of PEG-based microgels. We give examples illustrating their electrostatic deposition onto biomaterial surfaces and their ability to sequester antimicrobials for applications involving biomaterials-associated infection. [ABSTRACT FROM AUTHOR]

This paper reports a new approach towards the construction of a multifunctional periodic mesoporous organosilica (PMO), which integrates a range of advantages, such as mesoporous structural order, selective nucleobase-recognition properties, stimuli-responsive site-specific delivery of anticancer agents to cancer tissues, and Cu2+ adsorption, into a single entity. First, the appropriate organic-functional-receptor precursor was synthesized by a chemical process and used to fabricate a multifunctional pyridine-containing PMO material (DMPy-PMO) by a hydrolysis and condensation route. The designed organic-inorganic hybrid mesoporous silica chemosensor showed an intrinsic selective recognition of nucleobase, specifically thymidine, through multipoint hydrogen-bonding interactions with suitably arrayed receptor sites loaded into the rigid silica framework. An in vitro cytotoxicity test showed that the designed chemosensor materials have good biocompatibility and, therefore, could be promising candidates for the delivery of a range of therapeutic agents. Confocal laser scanning microscopy (CLSM) confirmed that the material can be internalized effectively by cancer cells (MCF-7 cells). In addition, the DMPy-PMOs showed efficient Cu2+ ion removal capacity at pH 5.0 with significantly high levels of adsorption (0.95 mmol g-1). These results suggest that the prepared multifunctional PMO hybrid has potential use as a smart material for a range of applications, such as biomolecule recognition, biomedical applications, and as an efficient adsorbent for the removal of metal ions. [ABSTRACT FROM AUTHOR]