Inside Back Cover: Tailored Core‐Shell Nanocarrier for Therapeutic Drug Delivery via Visible Light Activation

Over the past few years, nanocarriers have become an ideal solution for safe and efficient drug delivery and release. This is mainly due to the extraordinary characteristics that nanomaterials exhibit when compared with their larger scaled forms. A variety of these carriers are more popular due to their high biocompatibility, ensuring greater efficacy especially in cancer treatments. Nanocrystal, liposomal, and micelle designs of these materials as nanocarriers for drug delivery and release have been extensively researched throughout the past 50 years. Successful applications have not only ensured a greater focus on therapeutic development but also created a new solution available in the pharmaceutical market. Herein, a brief review of research studies focused on nanocarrier materials and designs to achieve superior benefits of drugs for disease treatments is presented. Nanohydrogels, chitosan, graphene oxide, and solid lipid nanoparticle nanocarrier designs and applications are selectively given due to the great attention they have gained from being highly biocompatible and easy-to-manipulate nanocarrier options from organic and inorganic nanocarrier materials. Each summary exhibits the progress that has been achieved to date. With greater understanding of the current state in the development process of these nanomaterials, there is a rising chance to provide better treatment to patients, which is a desperate need in pharmaceutical technologies.

Conventional treatment for eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is usually limited; consequently, relapses occur frequently, accurate local drug delivery is currently a research area of major interest. Based on postoperative nasal sinus computed tomography (CT) images, the 3D printing technique was used to design and fabricate a precise track-guided sinus drug delivery device. The control group was treated with glucocorticoids by nasal spray for 1year according to the conventional method, while the experimental group received topical nasal glucocorticoids using the 3D-printed track-guided precise sinus drug delivery device for 1 year. Scores on the Sino-Nasal Outcome Test (SNOT-22) scale and the Lund-Kennedy nasal endoscopic scale during reexamination at 1month, 3months, 6months, and 1year after the operation were used as the basis for evaluation. The follow-up duration was 12months or more following endoscopic sinus surgery (ESS) with neosinus cavity formation. The two groups showed significant differences in SNOT-22 scores and nasal polyp Lund-Kennedy subscores at 3months, 6months, and 1year (p < 0.001) and no differences in plasma cortisol at 6months and 1year (p > 0.05). Local drug administration using our 3D-printed precise sinus drug delivery device is superior to conventional nasal cavity administration in controlling eCRS recurrence.

Morphology-driven protein corona manipulation for preferential delivery of lipid nanodiscs

Stimuli-responsive amphiphilic polymers are known to be precursors to forming promising nanoarchitectonics with tunable properties for application in biomedical sciences. Currently, self-immolative polymers are widely recognized as an emerging class of responsive materials with excellent degradability, which is one of the crucial criteria for designing a robust drug delivery vehicle. Here, we design an amphiphilic polyurethane endowed with a redox-responsive self-immolative linker and a pH-responsive tertiary amine on the backbone, which forms entropy-driven nanoscale supramolecular assemblies (average hydrodynamic diameter ∼110 nm) and is programmed to disassemble in a redox environment (GSH) due to the degradation of the polymer in a self-immolative fashion. The nanoassembly shows efficient drug sequestration and release in a controlled manner in response to glutathione (10 mM). The tertiary amine residing on the surface of the nanoassembly becomes protonated in the tumor microenvironment (pH ∼ 6.4-6.8) and generates positively charged nanoassembly (ζ-potential = +36 mV), which enhances the cancer cell-selective cellular uptake. The biological evaluation of the drug-loaded nanoassembly revealed triple-negative breast cancer (MDAMB-231) selective internalization and cell death while shielding normal cells (RBCs or PBMCs) from off-targeting toxicity. We envision that polyurethane with a redox-responsive self-immolative linker might open up new opportunities for a completely degradable polyurethane-based nanocarrier for drug delivery and diagnosis applications.

Recently greater emphasis has been given to combination therapy for generating synergistic effects of treating cancer. Recent studies on thiol-sensitive nanocarriers for the delivery of drug or gene have shown promising results. In this review, we will examine the rationale and advantage in using nanocarriers for the combined delivery of different anticancer drugs and biologics. Here, we also discuss the role of nanocarriers, particularly redox-sensitive polymers in evading or inhibiting the efflux pump in cancer and how they modulate the sensitivity of cancer cells. The review aims to provide a good understanding of the new pattern of cancer treatment and key concerns for designing nanomedicine of synergistic combinations for cancer therapy.

Polymer micelles have proven to be one of the most versatile nanocarriers for anticancer drug delivery. However, the in vitro and in vivo stability of micelles remains a challenge due to the dynamic nature of these self-assembled systems, which leads to premature drug release and nonspecific biodistribution in vivo. Recently, reversibly crosslinked micelles have been developed to provide solutions to stabilize nanocarriers in blood circulation. Increased stability allows nanoparticles to accumulate at tumor sites efficiently via passive and/or active tumor targeting, while cleavage of the micelle crosslinkages, through internal or external stimuli, facilitates on-demand drug release. In this review, various crosslinking chemistries as well as the choices for reversible linkages in these nanocarriers will be introduced. Then, the development of reversibly crosslinked micelles for on-demand drug release in response to single or dual stimuli in the tumor microenvironment is discussed, for example, acidic pH, reducing microenvironment, enzymatic microenvironment, photoirradiation and the administration of competitive reagents postmicelle delivery.

Tunable sericin nanocarriers for controlled drug release and glioblastoma targeting

Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review

Harnessing inhaled nanoparticles to overcome the pulmonary barrier for respiratory disease therapy

Poor pharmacokinetics and low aqueous solubility combined with rapid clearance from the circulation of drugs result in their limited effectiveness and generally high therapeutic doses. The use of nanocarriers for drug delivery can prevent the rapid degradation of the drug, leading to its increased half-life. It can also improve the solubility and stability of drugs, advance their distribution and targeting, ensure a sustained release, and reduce drug resistance by delivering multiple therapeutic agents simultaneously. Furthermore, nanotechnology enables the combination of therapeutics with biomedical imaging agents and other treatment modalities to overcome the challenges of disease diagnosis and therapy. Such an approach is referred to as "theranostics" and aims to offer a more patient-specific approach through the observation of the distribution of contrast agents that are linked to therapeutics. The purpose of this paper is to present the recent scientific reports on polymeric nanocarriers for MRI-guided drug delivery. Polymeric nanocarriers are a very broad and versatile group of materials for drug delivery, providing high loading capacities, improved pharmacokinetics, and biocompatibility. The main focus was on the contrasting properties of proposed polymeric nanocarriers, which can be categorized into three main groups: polymeric nanocarriers (1) with relaxation-type contrast agents, (2) with chemical exchange saturation transfer (CEST) properties, and (3) with direct detection contrast agents based on fluorinated compounds. The importance of this aspect tends to be downplayed, despite its being essential for the successful design of applicable theranostic nanocarriers for image-guided drug delivery. If available, cytotoxicity and therapeutic effects were also summarized.

Rapid drug delivery is critical in emergency medical circumstances where delays can result in adverse or life-threatening outcomes. The sublingual route holds significant promise for the swift systemic delivery of drugs, but is limited by slow passive diffusion mechanisms that hinder efficient drug transport. To address these challenges, we introduce here a novel sublingual microrobotic pill platform designed for rapid and efficient drug delivery. Our system incorporates magnesium-based microstirrers that accelerate pill disintegration and drug release via an active propulsion mechanism. Such bubble-propelled microstirrers generate strong hydrodynamic flows, enhancing local mixing and drug transport, allowing them to overcome the limitations of traditional diffusion-dominated delivery systems. Optimized through in vitro studies, this platform demonstrated robust motion capabilities in complex human saliva and accelerated drug release kinetics. In a rabbit model, using epinephrine as the model drug, the sublingual microrobotic pill achieved significantly faster drug delivery speed, efficiency, and bioavailability compared to a conventional pill. Moreover, when compared against the gold standard intramuscular injections, the microstirring pill provides competitive delivery speed and enhanced absorption profile, demonstrating its potential for use in the treatment of conditions like anaphylactic shock. Such user-friendly, non-invasive sublingual microrobotic pills can be readily employed for delivering a wide range of drugs, offering a versatile solution for acute conditions requiring rapid therapeutic onset or when enteral absorption is not feasible.

Dimer Targeting Peptide Mediated Precise and Controllable Drug Delivery by Upconversion Nanocarriers for Breast Cancer Therapy

Stepwise pH-sensitive and biodegradable polypeptide hybrid micelles for enhanced cellular internalization and efficient nuclear drug delivery

Wireless implantable drug delivery systems (DDSs) enable targeted, on-demand drug release to maximize therapeutic efficacy. Ultrasound has been proposed to wirelessly power and control millimeter-sized deeply implantable DDSs, but initial demonstrations encountered challenges in power transfer and release control reliability in dynamic in vivo environments. In this work, we present a closed-loop implantable DDS using ultrasound wireless power and communication in conjunction with an electrochemical drug release mechanism. The system consists of piezoelectric transducers for wireless power and data transmission, a drug delivery module containing drug-loaded electroresponsive nanoparticles, and a custom CMOS integrated circuit for closed-loop drug release using a programmable potentiostat capable of providing potentials up to $\boldsymbol{\pm}$1.5 V and sensing current up to $\boldsymbol{\pm}$100 $\boldsymbol{\mu}$A. The chip also improves power transfer robustness by enabling ultrasound power combining and rectifier voltage feedback which can be used to adapt the power transmitter and minimize misalignment. Closed-loop release control is tested in vitro using the wirelessly powered DDS at 8cm depth by adjusting the potentiostat stimulus voltage based on feedback of redox current into fluorescein-loaded nanoparticles, resulting in consistent 2 $\boldsymbol{\mu}$g release across different fluorescein loading concentrations and a 39$\%$ reduction in release amount variation. These results demonstrate the effectiveness of closed-loop release control in enabling precise and reliable drug delivery.

Nanoparticulate systems made of biopolymers encompass promising properties as carriers and adjuvant for drug delivery. Alginate is one of the most widely investigated biomaterials in the field of nanoparticulate drug delivery due to its biodegradability, biocompatibility, and bioadhesivity. Alginate nanoparticles for drug delivery can be prepared through spray drying, ionic gelation, emulsification, covalent cross-linking, polyelectrolyte complexation, self-assembling, etc. Alginate is an extensively utilized biopolymer in multiple applications due to its gelling property and chemical structure with hydroxyl and carboxylate moieties. The biocompatibility, biodegradability of alginate, and solubility in water have broadened up research perspectives in material, and biomedical sciences. Study of alginate-based nanoparticles, nanoaggregates, and nanofibers initiated recently. In the present review, the physicochemical properties of alginate, which enabled its use as a pharmaceutical excipient and as nanocarriers in drug delivery, have been reviewed. A special insight has been given on the modern advances of alginate nanoparticles in drug delivery and drug targeting applications. Besides this, limitations of alginate as nanocarriers in drug delivery and the future perspectives on how to augment utilization in the pharmaceutical nanotechnology have also been reviewed.