Drug Delivery Profile Research Articles

Structure-Based Varieties of Polymeric Nanocarriers and Influences of Their Physicochemical Properties on Drug Delivery Profiles.

Carriers are equally important as drugs. They can substantially improve bioavailability of cargos and safeguard healthy cells from toxic effects of certain therapeutics. Recently, polymeric nanocarriers (PNCs) have achieved significant success in delivering drugs not only to cells but also to subcellular organelles. Variety of natural sources, availability of different synthetic routes, versatile molecular architectures, exploitable physicochemical properties, biocompatibility, and biodegradability have presented polymers as one of the most desired materials for nanocarrier design. Recent innovative concepts and advances in PNC‐associated nanotechnology are providing unprecedented opportunities to engineer nanocarriers and their functions. The efficiency of therapeutic loading has got considerably increased. Structural design‐based varieties of PNCs are widely employed for the delivery of small therapeutic molecules to genes, and proteins. PNCs have gained ever‐increasing attention and certainly paves the way to develop advanced nanomedicines. This article presents a comprehensive investigation of structural design‐based varieties of PNCs and the influences of their physicochemical properties on drug delivery profiles with perspectives highlighting the inevitability of incorporating both the multi‐stimuli‐responsive and multi‐drug delivery properties in a single carrier to design intelligent PNCs as new and emerging research directions in this rapidly developing area.

Nanostructured hyaluronic acid-based hydrogels encapsulating synthetic/ natural hybrid nanogels as promising wound dressings

Hydrogels with nanostructured morphology formed by embedding polymeric nanoparticles in a biodegradable polymer matrix have gained considerable interest in the medical field due to improved drug delivery profiles and tissue-mimicking architecture. Moreover, through hydrogels biodegradation, the encapsulated nanoparticles are released and can easily enter in different compartments of the body, thus having the potential to control the delivery of short half-life drugs. Therefore, this study was devoted to preparation and characterization of nanostructured hybrid hydrogels by incorporating well-defined maleoyl-chitosan/poly(aspartic acid) (MAC5/PAS) nanogels into a polymer network based on thiolated hyaluronic acid (HASH) for wound dressings applications. The MAC5/PAS nanogels were used not only as nanocarriers for amoxicillin (Amox) encapsulation and control over its release through the HASH hydrogel network, but also as building blocks for hydrogel preparation. The obtained nanocomposite hydrogels exhibited a reduced swelling capacity and a controlled degradation rate in comparison with the non‐filled HASH hydrogel. In vitro release profile revealed the influence of environment pH on Amox delivery, a rapid release of drug being observed at pH 5.4. Moreover, the in vitro and in vivo assays revealed a good biocompatibility of hydrogels, highlighting the potential of these systems as therapeutic scaffolds for dressing applications.

Theoretical model for diffusion-reaction based drug delivery from a multilayer spherical capsule

Controlled drug delivery from a multilayer spherical capsule is used for several therapeutic applications. Developing a theoretical understanding of mass transfer in the multilayer capsule is critical for understanding and optimizing targeted drug delivery. This paper presents an analytical solution for the mass transport problem in a general multilayer sphere involving diffusion as well as drug immobilization in various layers due to binding reactions. An eigenvalue-based solution for this multilayer diffusion-reaction problem is derived in terms of various non-dimensional quantities including Sherwood and Damköhler numbers. It is shown that unlike diffusion-reaction problems in heat transfer, the present problem does not admit imaginary eigenvalues. The effect of binding reactions represented by the Damköhler numbers and outer surface boundary condition represented by the Sherwood number on drug delivery profile is analyzed. It is shown that a low Sherwood number not only increases drug delivery time, but also reduces the total mass of drug delivered. The mass of drug delivered is also shown to reduce with increasing Damköhler number. The impact of shell thickness is analyzed. The effect of a thin outer coating is accounted for by lumping the mass transfer resistance in series with convective boundary resistance, and a non-dimensional number involving the thickness and diffusion coefficient of the coating is shown to govern its impact on drug delivery characteristics. The analytical model presented here improves the understanding of mass transfer in a multilayer spherical capsule in presence of binding reactions, and may help design appropriate experiments for down-selecting candidate materials and geometries for drug delivery applications of interest.

Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles.

Lipophilic conjugates (LCs) of small molecule drugs have been used widely in clinical and pre-clinical studies to achieve a number of pharmacokinetic and therapeutic benefits. For example, lipophilic derivatives of drugs are employed in several long acting injectable products to provide sustained drug exposure for hormone replacement therapy and to treat conditions such as neuropsychiatric diseases. LCs can also be used to modulate drug metabolism, and to enhance drug permeation across membranes, either by increasing lipophilicity to enhance passive diffusion or by increasing protein-mediated active transport. Furthermore, such conjugation strategies have been employed to promote drug association with endogenous macromolecular carriers (e.g. albumin and lipoproteins), and this in turn results in altered drug distribution and pharmacokinetic profiles, where the changes can be 'general' (e.g. prolonged plasma half-life) or 'specific' (e.g. enhanced delivery to specific tissues in parallel with the macromolecular carriers). Another utility of LCs is to enhance the encapsulation of drugs within engineered nanoscale drug delivery systems, in order to best take advantage of the targeting and pharmacokinetic benefits of nanomedicines. The current review provides a summary of the mechanisms by which lipophilic conjugates, including in combination with delivery vehicles, can be used to control drug delivery, distribution and therapeutic profiles. The article is structured into sections which highlight a specific benefit of LCs and then demonstrate this benefit with case studies. The review attempts to provide a toolbox to assist researchers to design and optimise drug candidates, including consideration of drug-formulation compatibility.

Fully supercritical CO2 preparation of a nanostructured MOF composite with application in cutaneous drug delivery

Supercritical CO2 (scCO2) technology is used here as an efficient method to assist in the preparation of a cutaneous polymeric formulation based on drug containing metal-organic framework composites. The supercritical fluid is used in three steps: (i) as a drying agent for the nanosized mesoporous matrix, (ii) as the impregnation vector of a topical antibiotic drug, and (iii) as a plasticizing and foaming fluid to obtain dispersions of the hybrid material into a biocompatible polymer, e.g., the macroporous patch. The materials were characterized using solid state techniques. The drug delivery and permeation profiles of the patches were investigated applying in vitro and ex vivo tests by using porcine skin. These analyses suggest that scCO2 impregnation is an easy and fast strategy to prepare composite devices able to progressively release and diffuse the incorporated drug throughout the skin, paving the way to efficiently prepare cutaneous devices for topical or systemic therapies.

Topical NSAIDs for acute local pain relief: in vitro characterization of drug delivery profiles into and through human skin

Objective The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) relates not only to the individual NSAID used but also to differences in formulation design. The aim of this study was to investigate the fundamental differences in ibuprofen and diclofenac drug delivery vehicles, specifically gels and plasters, compared to a recently launched 200 mg ibuprofen medicated plaster and characterize the resulting dermatologic–pharmacokinetic profiles into and through ex vivo human skin layers. Methods In vitro skin permeation testing over 24 h and sacrificial timepoint penetration experiments (at 1, 4, 8, 12, and 24 h) were conducted using an automated flow-through diffusion cell system. The amount of drug delivered to the epidermis, dermis, and receptor solution (representing deeper tissue) was determined by liquid chromatography-tandem mass spectrometry. Skin protein binding of ibuprofen and diclofenac was investigated by spiking skin homogenate with increasing concentrations of each drug and determining the fraction unbound. Results Differences were observed in the amount of drug recovered at sacrificial timepoints and rate at which drug was delivered to the target site between plaster and gel formulations of ibuprofen and diclofenac and between plaster formulations of the same drug (ibuprofen). While the amount of drug quantified at sacrificial timepoints did not necessarily determine in vivo flux rates, differences in drug distribution within the skin layers indicated where drug reservoirs were formed. Conclusions These findings highlight the importance of intelligent formulation design in determining NSAID delivery through skin layers. Further work is required to quantify drug delivery into deeper tissues and the resultant local anti-inflammatory effects.

In situ drug release measuring in \u03b1-TCP cement by electrochemical impedance spectroscopy

The use of drug delivery systems is a good technique to leave the right quantity of medicine in the patient’s body in a suitable dose, because the drug application is delivered directly to the affected region. The current techniques such as HPLC and UV–Vis for the drug delivery calculation has some disadvantages, as the accuracy and the loss of the sample after characterization. With the aim of reducing the amount of material used during the characterization and have a non-destructive test with instantaneous results, the present paper shows the possibility of using electrochemical impedance spectroscopy (EIS) to have a drug delivery measurement during the release phenomena for a calcium phosphate cement (CFC) delivery system with gentamicin sulfate (GS) and lidocaine hydrochloride (LH), at a ratio of 1% and 2%, respectively. The equivalent circuit and the chemical mechanism involved during the measurements have been proposed as a tool to determine the drug delivery profile. The method has been compared with the UV–Vis technique. XRD was realized to verify conditions, before and after release. It was possible to verify the potential for using EIS as an instant technique to quantify drug delivery.

Controlled SrR Delivery by the Incorporation of Mg Particles on Biodegradable PLA-Based Composites.

Among several ions playing a vital role in the body, Sr2+ and Mg2+ are involved in the mechanism of bone formation, making them especially useful for bone tissue engineering applications. Recently, polylactic acid (PLA)/Mg composites have emerged as a promising family of biomaterials due to their inherent biocompatibility and biodegradability properties. In these composites, polymer and bio-metal have a synergetic effect—while the PLA inhibits the Mg fast reactivity, Mg provides bioactivity to the inert polymer buffering the medium pH during degradation. Meanwhile, the typical form of administrating Sr2+ to patients is through the medication strontium ranelate (SrR), which increases the bone mineral density. Following this interesting research line, a new group of composites, which integrates Mg particles and SrR charged onto halloysite nanotubes (HNT) in a polymeric matrix, was proposed. PLA/Mg/SrR–HNT composites have been processed following a colloidal route, obtaining homogenous composites granulated and film-shaped. The drug delivery profile was evaluated in terms of in vitro lixiviation/dissolution paying special attention to the synergism of both ions release. The combination of two of the most reported ions involved in bone regeneration in the composite biomaterial may generate extra interest in bone healing applications.

Drug delivery and in vitro biological effects of gum ghatti-modified hydroxyapatite nanoporous composites

The present study investigates the influence of gum ghatti (GG) concentration on the porosity of hydroxyapatite (HAP), where the final composite has been tested for the effects of drug delivery, antibacterial activity, and in vitro cytotoxicity. Following the synthesis of GG-HAP composite by a simple chemical precipitation method, the various analyses were employed to understand the crystallinity, morphology, chemical composition, surface functionality and internal bonding, etc. From the comparison of physical properties among the sintered and un-sintered GG-HAP composites and that too with different concentrations of GG (1%, 5%, and 10%), we observed the superior properties for the samples formed from higher GG concentration (10%) with sintering. We observed the lowest crystal size of 30 nm with 95% crystallinity, a surface area of 108 m2/g, a total pore volume of 0.2 mL/g, an average pore diameter of 33 Å for the Sin-10% GG-HAP composite. In addition, the biocompatibility test performed on the Sin-GG-HAP pellet confirmed the in-built bioactivity and biostability of the composites in simulated body fluid. Further, the Naringenin drug delivery profiles confirmed for the stable and controlled release of loaded drug from the Sin-GG-HAP composites (with 1, 5, and 10% of GG). We observed the highest release of 96% from the Sin-10% GG-HAP matrix in just 90 min and T50% of 416 h, and a mean diffusion time period of 459 h. Finally, the antimicrobial (using both gram-positive and gram-negative bacteria) and cytotoxic activities (with the use of healthy normal and diseased cells) of the drug-loaded and un-loaded GG-HAP composites confirm the potential role of the formed Sin-10% GG-HAP composite towards biomedical applications.

A New Long-Term Composite Drug Delivery System Based on Thermo-Responsive Hydrogel and Nanoclay.

Several problems and limitations faced in the treatment of many diseases can be overcome by using controlled drug delivery systems (DDS), where the active compound is transported to the target site, minimizing undesirable side effects. In situ-forming hydrogels that can be injected as viscous liquids and jellify under physiological conditions and biocompatible clay nanoparticles have been used in DDS development. In this work, polymer–clay composites based on Pluronics (F127 and F68) and nanoclays were developed, aiming at a biocompatible and injectable system for long-term controlled delivery of methylene blue (MB) as a model drug. MB release from the systems produced was carried out at 37 °C in a pH 7.4 medium. The Pluronic formulation selected (F127/F68 18/2 wt.%) displayed a sol/gel transition at approx. 30 °C, needing a 2.5 N force to be injected at 25 °C. The addition of 2 wt.% of Na116 clay decreased the sol/gel transition to 28 °C and significantly enhanced its viscoelastic modulus. The most suitable DDS for long-term application was the Na116-MB hybrid from which, after 15 days, only 3% of the encapsulated MB was released. The system developed in this work proved to be injectable, with a long-term drug delivery profile up to 45 days.

Milling of poorly soluble crystalline drug compounds to generate appropriate particle sizes for inhaled sustained drug delivery.

One of the simplest design concepts of inhaled sustained drug delivery to the lung is to utilize the slow dissolution of drug crystals with poor aqueous solubility. An optimum dissolution rate, and thereby a delivery profile locally in the lung tissue, can be achieved in a reliable way by selecting a compound with an appropriate combination of solubility and particle size. It is in our experience relatively straightforward to manufacture monomodal particle size distributions of poorly soluble drug crystals in the mass median diameter range of either a few micrometers or a few hundred nanometers, but very challenging to manufacture a monomodal distribution in the range intermediate to these two. In this manuscript, we describe an investigation with the objective of generating desired particle sizes in the whole size range from a few micrometers to a few hundred nanometers for inhaled sustained drug delivery, by utilizing Adaptive Focused Acoustic (AFA) milling and planetary bead-milling. By combining the two different milling techniques it was possible to produce two to three distinctly different monomodal or almost monomodal particle size distributions in the desired particle size range of each of the model drug compounds in milligram scale. The dissolution kinetics of the different particle sizes of the model drugs were measured experimentally as well as predicted theoretically, showcasing that the dissolution kinetics can be characterized, predicted and significantly changed in a controlled way by modifying the particle size. For one of the model drugs, it was shown in an in vivo rat study that the inhaled sustained drug delivery profile in the lung tissue could be significantly changed by modifying the particle size of the drug.

Affinity-Based Polymers Provide Long-Term Immunotherapeutic Drug Delivery Across Particle Size Ranges Optimal for Macrophage Targeting.

Drug delivery to specific arms of the immune system can be technically challenging to provide prolonged drug release while limiting off-target toxicity given the limitations of current drug delivery systems. In this work, we test the design of a cyclodextrin (CD) polymer platform to extend immunomodulatory drug delivery via affinity interactions for sustained release at multiple size scales. The parameter space of synthesis variables influencing particle nucleation and growth (pre-incubation time and stirring speed) and post-synthesis grinding effects on resulting particle diameter were characterized. We demonstrate that polymerized CD forms exhibit size-independent release profiles of the small molecule drug lenalidomide (LND) and can provide improved drug delivery profiles versus macro-scale CD polymer disks in part due to increased loading efficiency. CD polymer microparticles and smaller, ground particles demonstrated no significant cytotoxicity as compared to the base CD monomer when co-incubated with fibroblasts. Uptake of ground CD particles was significantly higher following incubation with RAW 264.7 macrophages in culture over standard CD microparticles. Thus, the affinity/structure properties afforded by polymerized CD allow particle size to be modified to affect cellular uptake profiles independently of drug release rate for applications in cell-targeted drug delivery.

Statistical Considerations in Assessing In Vivo Adhesion with Transdermal and Topical Delivery Systems for New Drug Applications.

Proper adhesion plays a critical role in maintaining a consistent, efficacious, and safe drug delivery profile for transdermal and topical delivery systems (TDS). As such, in vivo skin adhesion studies are recommended by regulatory agencies to support the approval of TDS in new drug applications (NDAs). A draft guidance for industry by the US Food and Drug Administration outlines a non-inferiority comparison between a test product and its reference product for generic TDS in abbreviated new drug applications (ANDAs). However, the statistical method is not applicable for evaluating adhesion of TDS for NDAs, because no reference product exists. In this article, we explore an alternative primary endpoint and a one-sided binomial test to evaluate in vivo adhesion of TDS in NDAs. Statistical considerations related to the proposed approach are discussed. To understand its potential use, the proposed approach is applied to data sets of in vivo adhesion studies from selected NDAs and ANDAs.

Motion Capture Quantification of User Variation in Topical Microparticle Application.

Motion capture has the potential to shed light on topical drug delivery application. This approach holds promise both as a training tool, and for the development of skin technology, but first, this approach requires validation. Elongated microparticles (EMP) are a physical delivery enhancement technology that relies on a user working in the microparticles using a textured applicator. We used this approach to test the hypothesis that motion capture data can be used to characterize the topical application process. Motion capture was used to record participants while applying a mixture of EMP and sodium fluorescein to ex-vivo porcine skin samples. Treated skin was assessed using reflectance confocal and fluorescence microscopy. Image analysis was used to quantify the microparticle density and the presence of a fluorescent drug surrogate, sodium fluorescein. A strong correlation was present between applicator motion and microparticle and drug delivery profiles. There were quantitative and qualitative differences in the intra- and inter- user application methods that went beyond the level of training. Frequency and velocity of the applicator motion were key factors that correlated with EMP density. Our quantitative analysis of an experimental dermatological device supports the hypothesis that self-application may benefit from some form of digital monitoring or training with feedback. Our conclusion is that the integration of motion capture into experimental dermatological research offers an improved and quantifiable perspective that could be broadly useful with respect to topical applications, and with respect to the instruction provided to patients and clinicians.

Computer Modeling of Drug Delivery with Thermosensitive Liposomes in a Realistic Three-Dimensional Geometry.

Thermosensitive liposomes (TSL) are nanoparticles that can encapsulate therapeutic drugs, and release those drugs when exposed to hyperthermic temperatures (>40 °C). Combined with localized hyperthermia, TSL enable focused drug delivery. In this study, we created a three-dimensional (3D) computer model for simulating delivery with TSL-encapsulated doxorubicin (TSL-Dox) to mouse tumors. A mouse hind limb was scanned by a 3D scanner and the resulting geometry was imported into finite element modeling software, with a virtual tumor added. Then, heating by a surface probe was simulated. Further, a drug delivery model was coupled to the heat transfer model to simulate drug delivery kinetics. For comparison, experimental studies in gel phantoms and in vivo fluorescence imaging studies in mice carrying lung tumor xenografts were performed. We report the tissue temperature profile, drug concentration profile and compare the experimental studies with the computer model. The thermistor produced very localized heating that resulted in highest drug delivery to regions near the probe. The average tumor temperature was 38.2˚C (range 34.4-43.4˚C), and produced an average tumor drug concentration of 11.8 µg/g (0.3-28.1 µg/g) after 15 min heating, and 25.6 µg/g (0.3-52 µg/g), after 60 min heating. The computer model reproduced the temperature profile compared to phantom experiments (mean error 0.71 °C, range 0.59-1.25 °C), as well as drug delivery profile as compared to in vivo studies. Our results suggest feasibility of using this approach to model drug delivery in preclinical studies with accurate model geometry.

Local Immunosuppression for Vascularized Composite Allografts: Application of Topical FK506-TyroSpheres in a Nonhuman Primate Model.

Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA. Current formulations are limited though, by poor skin penetration but this may be mitigated by conjugation of immunosuppressive drugs to TyroSpheres for enhanced delivery. Therefore, we investigated the topical application of FK506-TyroSpheres (in the form of a gel dressing) in a clinically relevant nonhuman primate VCA model to determine if allograft survival could be prolonged at reduced levels of maintenance systemic immunosuppression. Six Major Histocompatibility Complex (MHC)-mismatched cynomolgus macaques (Macaca fascicularis) served as reciprocal donors and recipients of radial forearm fasciocutaneous flaps. Standard Bacitracin ointment and FK506-TyroSpheres were applied every other day to the VCAs of animals in groups 1 (controls, n = 2) and 2 (experimental, n = 4), respectively, before gradual taper of systemic FK506. Clinical features of VCA rejection still developed when systemic FK506 fell below 10 ng/ml despite application of FK506-TyroSpheres and prolonged VCA survival was not achieved. However, unwanted systemic FK506 absorption was avoided with TyroSphere technology. Further refinement to optimize local drug delivery profiles to achieve and maintain therapeutic delivery of FK506 with TyroSpheres is underway, leveraging significant experience in controlled drug delivery to mitigate acute rejection of VCAs.

Targeting primary cilia with polymeric nanoparticles

The field of nanomedicine is a promising future in providing huge clinical impacts on advanced disease management and personalized medicine. Nanoparticles (NPs) have been used for targeted delivery at a desired site and a sustained release of a drug, which decreases the overall toxicity by delivering a smaller drug dosage. An extensively investigated NPs is poly lactic‐co‐glycolic acid (PLGA) which is an FDA approved biodegradable polymer and they are currently used in clinical setting. Hence in our current study, we used PLGA nanoparticles labeled with dopamine receptor 5 antibody to target primary cilia. Further these NPs were loaded with fenoldopam to improve cilia structure and function. The conjugation and loading was confirmed by UV‐visible spectroscopy, transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), zeta potential measurements and Fourier transform infrared spectroscopy (FTIR). TEM confirmed the synthesized nanoparticles were around 120 nm and spherical in shape. FTIR confirms the drug loading and antibody interactions with the PLGA. When we injected these NPs to ciliopathic hypertensive mice, significantly improved cardiac function in the ciliopathic hypertensive models, in which the hearts also exhibited arrhythmia, which was corrected with the PLGA‐NPs. Intraciliary and cytosolic Ca2+ were increased when cilia were induced with fluid flow, and this served as a cilia‐dependent mechanism of the PLGA‐NPs. Fenoldopam‐alone caused an immediate decrease in blood pressure, followed by hypertrophy with compromised functions in left ventricle pressure, stroke volume, ejection fraction. Our drug delivery profiles confirmed that the PLGA‐NPs were a potential delivery system for targeting cilia more specifically, efficiently, and effectively than fenoldopam‐alone. In conclusion, our results indicate that nanomedicine provides a possibility for targeted ciliotherapy.Support or Funding InformationThis work was supported by the National Institute of Health (HL131577), Congressionally Directed Medical Research Program (PR130153) and American Heart association (19IPLOI34730020).

Synthesis and characterization of binary selenides of transition metals to investigate its photocatalytic, antimicrobial and anticancer efficacy

Development of resilient and efficient composite materials that exhibit substantial antimicrobial activity, ample photocatalytic ability and considerable capacity for drug delivery is highly desirable. The present study demonstrates the incorporation of selenium (Se) in transition metals (vanadium-V, niobium-Nb, and tantalum-Ta) via standard solid-state hydrothermal reaction method. Generated nanostructures (V:Se, Nb:Se, Ta:Se) were characterized using various techniques. XRD analysis confirmed the presence of monoclinic phase compounds while crystallite size (~ 13.5–26.2 nm) was calculated using Debye–Scherrer equation. FESEM was used to examine surface morphologies of V:Se (rod-like and disc-shaped) and of Nb and Ta selenides (irregular agglomerated nanospheres). Compositional and functional group analysis was undertaken through FTIR spectroscopy and EDS coupled with SEM, respectively. Raman spectroscopy was carried out to ascertain the bending and stretching vibrational modes in samples. Optical properties were investigated through UV–Vis spectroscopy and the PL emission spectra were acquired to evaluate the charge separation and recombination behavior of compounds. Thermal stability of designed composites was measured using TGA/DSC. Potential uses of the prepared nanoparticles were explored in multiple fields including photocatalysis, antimicrobial and drug delivery systems. Methylene blue dye was degraded under 400–700 nm wavelength in the presence of synthesized wide band gap composites as photocatalysts. The selenium–metal particles were subjected as antimicrobial agents against gram (−ve) and gram (+ve) bacteria and experimental results suggested this material to be an effective antibiotic. Furthermore, synthesized nanocomposites were examined as carrier of anticancer drug (DOX) and their drug delivery profile was also investigated.

Magnetic Hybrid Wax Nanocomposites as Externally Controlled Theranostic Vehicles: High MRI Enhancement and Synergistic Magnetically Assisted Thermo/Chemo Therapy.

To fight against cancer, smarter drugs and drug delivery systems are required both to boost the efficiency of current treatments while reducing deleterious side effects, and combine diagnosis/monitoring with therapy (theranosis) in the search for the final goal of personalized medicine. This work presents the design, preparation, and proof-of-principle validation of a novel hybrid organic-inorganic nanocomposite joining together non-invasive imaging capabilities through magnetic resonance imaging and externally actuated therapeutic properties through a combination of chemo- and thermotherapy. The lipidic matrix of the nanocomposite was composed of carnauba wax, which was simultaneously dual loaded with magnetite nanoparticles and the anticancer drug Oncocalyxone A. Obtained formulations were fully characterized and showed outstanding performances as T2 -contrast agents in magnetic resonance imaging (r2 >800 mm-1 s-1 ), heat generating sources in magnetic hyperthermia (specific absorption rate, SAR>200 W g-1 Fe ), and magnetically responsive drug delivery vehicles. The potential of the designed formulations as theranostic agents was validated in vitro and results indicated a synergistic thermo/chemotherapeutic effect derived from heat generation and controlled drug delivery to cancer growth. Thereby, this external control over the drug delivery profile and the integrated imaging capability open the door to personalized cancer medicine and real-time monitoring of tumor progression.

Recent insights on nanomedicine for augmented infection control.

Antimicrobial agents have been widely investigated for protecting against microbial infections in modern health. Drug-related limitations, poor bioavailability, toxicity to mammalian cells, and frequent bacteria drug resistance are major challenges faced when exploited in nanomedicine forms. Specific attention has been paid to control nanomaterial-based infection against numerous challenging pathogens in addition to improved drug delivery, targeting, and pharmacokinetic (PK) profiles, and thus, efficient antimicrobials have been fabricated using diverse components (metals, metal oxides, synthetic and semisynthetic polymers, natural or biodegradable polymers, etc). The present review covers several nanocarriers delivered through various routes of administration, highlighting major findings to control microbial infection as compared to using the free drug. Results over the past decade support the consistent development of various nanomedicines capable of improving biological significance and therapeutic benefits against an array of microbial strains. Depending on the intended application of nanomedicine, infection control will be challenged by various factors such as weighing the risk–benefits in healthcare settings, nanomaterial-induced (eco)toxicological hazards, frequent development of antibiotic resistance, scarcity of in vivo toxicity data, and a poor understanding of microbial interactions with nanomedicine at the molecular level. This review summarizes well-established informative data for nanomaterials used for infection control and safety concerns of nanomedicines to healthcare sectors followed by the significance of a unique “safe-by-design” approach.