Stimuli-responsive Drug Delivery Systems Research Articles

Innovative ocular drug delivery systems: A comprehensive review of nano formulations and future directions

The eye's intricate structure and blood-ocular barriers pose significant challenges to effective ocular drug delivery. The blood-retinal barrier and blood-aqueous barrier restrict drug penetration, leading to poor bioavailability and limited treatment options for ocular diseases. Various administration routes, including systemic, topical, intravitreal, subconjunctival, and intracameral, have been explored to overcome these barriers. Nanotechnology-based platforms, such as liposomes, nanoemulsions, nanomicelles, nanosuspensions, and niosomes, have shown promise in enhancing ocular drug delivery. These platforms offer improved solubility, stability, and targeted release, increasing the efficacy of treatments for conditions like age-related macular degeneration, cataracts, diabetic retinopathy, fungal keratitis, and retinoblastoma. Future perspectives focus on developing minimally invasive, sustained-release systems that maintain intraocular efficacy. Nanofibers and stimuli-responsive drug delivery systems also hold potential for overcoming ocular delivery challenges.

Nanotechnology-Based Drug Delivery Systems for Chemotherapy: A Review of Current Approaches and Future Prospects

Nanotechnology-based drug delivery systems have developed as a novel approach to cancer treatment, notably chemotherapy, with higher precision, efficacy, and less side effects than traditional approaches. Chemotherapy, while successful in targeting rapidly dividing cancer cells, frequently encounters considerable hurdles such as systemic toxicity, non-targeted drug distribution, and resistance. Nanotechnology offers a promising alternative for targeted delivery, controlled release, and overcoming multidrug resistance (MDR). Various nanocarriers, such as liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, have been developed to improve drug delivery by leveraging the increased permeability and retention (EPR) effect for tumour targeting. The design of these nanocarriers, which includes size, surface qualities, and functionality, provides longer circulation time, increased tumour formation, and fewer side effects on healthy tissues. Despite multiple clinical achievements, such as the FDA's clearance of nanomedicines like Doxil and Abraxane, there are still obstacles in translating these technologies from laboratory research to clinical practice. Nanoparticle stability, scalability, regulatory barriers, and cytotoxicity are all important considerations. This study examines the current state of nanotechnology-based drug delivery systems, emphasizing clinical accomplishments, problems, and upcoming technologies such as stimuli-responsive and AI-assisted drug delivery systems. The future of cancer treatment is in the creation of smart nanocarriers that can combine chemotherapy with other therapeutic modalities such as immunotherapy, gene therapy, and photodynamic therapy. Hence, personalized nanomedicine, which tailors drug delivery systems to individual patients' genetic profiles and tumour features, is a promising future direction. Overall, this review seeks to investigate the most recent developments and future prospects in nanotechnology-driven chemotherapy.

Temperature and Ultrasound-Responsive Nanoassemblies for Enhanced Organ Targeting and Reduced Cardiac Toxicity.

Biocompatible nanocarriers are widely employed as drug-delivery vehicles for treatment. Nevertheless, indiscriminate drug release, insufficient organ-specific targeting, and systemic toxicity hamper nanocarrier effectiveness. Stimuli-responsive nano-sized drug delivery systems (DDS) are an important strategy for enhancing drug delivery efficiency and reducing unexpected drug release. This study introduces a temperature- and ultrasound-responsive nano-DDS in which the copolymer p-(MEO2MA-co-THPMA) is grafted onto mesoporous iron oxide nanoparticles (MIONs) to construct an MPL-p nano-DDS. The copolymer acts as a nanopore gatekeeper, assuming an open conformation at sub-physiological temperatures that allows drug encapsulation and a closed conformation at physiological temperatures that prevents unexpected drug release during circulation. Lactoferrin was conjugated to the nanoparticle surface via polyethylene glycol to gain organ-targeting ability. External ultrasonic irradiation of the nanoparticles in the targeted organs caused a conformational change of the copolymer and reopened the pores, facilitating controlled drug release. MPL-p exhibited excellent biocompatibility and rare drug release in circulation. When targeting delivery to the brain, ultrasound promoted the release of the loaded drugs in the brain without accumulation in other organs, avoiding the related adverse reactions, specifically those affecting the heart. This study established a novel temperature- and ultrasound-responsive DDS that reduced systemic adverse reactions compared with traditional DDS, especially in the heart, and demonstrated excellent organ delivery efficiency.

Preparation and in vitro evaluation of pH and glutathione dual-responsive drug delivery system based on sodium carboxymethyl cellulose

Stimuli-responsive drug delivery systems based on sodium carboxymethyl cellulose (NaCMC) for drug release encounter inherent challenges. In this research, a novel pH and glutathione (GSH) dual-responsive system, CPT-S-S-NaCMC@ZIF-8/SP-PEG, was constructed. Firstly, the prodrug CPT-S-S-OH was synthesized and combined with NaCMC to form GSH-responsive micelles CPT-S-S-NaCMC, significantly enhancing the drug loading and grafting rates to 63.79 % and 91.99 %, respectively. Subsequently, zinc ions and dimethylimidazole can be assembled into porous materials (ZIF-8) on the surface of the micelles. This system exhibits dual pH-GSH responsiveness and effectively reduces the drug release from 84.76 % to 28.71 % at pH = 7.4. Moreover, incorporating pH-responsive spiropyran (SP)-modified polyethylene glycol (PEG) can reduce drug leakage to 16.09 % at pH = 7.4 and exhibit good fluorescence intensity at 722 nm.

Triggering multiple modalities of cell death via dual-responsive nanomedicines to address the narrow therapeutic window of β-lapachone

The clinical translation of the anticancer drug β-lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways (e.g., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.

Self-Indicating Polymer Prodrug Nanoparticles for pH-Responsive Drug Delivery in Cancer Cells and Real-Time Monitoring of Drug Release.

Amphiphilic self-indicating and responsive polymer-based prodrugs have generated much interest as potential stimuli-responsive intelligent drug delivery systems (DDS) due to their ability to selectively deliver drugs to the cancer cells and to monitor real-time cellular uptake of the drug by imaging technique(s). In this direction, we have synthesized a new pH-responsive N-vinyl-2-pyrrolidone and coumarin-based fluorescent self-indicating polymeric prodrug (SIPD), poly(NVP)-b-poly(FPA.DOX-r-FPA-r-CA). This block copolymer prodrug self-assembled into stable micellar nanoparticles under physiological conditions that reduced undesirable drug leakage to normal cells but resulted in the release of the anticancer drug doxorubicin (DOX) in cancer cells because of acidic pH-induced cleavage of imine bonds between DOX and the copolymer. While the polymer was found to be highly biocompatible with both normal (HEK-293) cells and cancer (MCF-7) cells even at high concentrations by MTT assay, the polymer prodrug nanoparticles showed toxicity even higher than that of free DOX in cancer cells. Phase contrast microscopy also depicted the cytotoxic effects of the nanoparticles on cancer cells. The coumarin units present in the polymer served as a fluorescence resonance energy transfer (FRET) pair with the covalently attached DOX molecules, which was established by steady-state and time-resolved fluorescence spectroscopy. Furthermore, confocal microscopy results confirmed the FRET phenomenon, as the fluorescence intensity of coumarin in the micellar nanoparticles remained quenched initially in MCF-7 cells but recovered with time as the DOX molecules were released and gradually shifted toward the targeted nucleus. All of these studies implied that the synthesized prodrug nanoparticles may provide another viable option for delivering chemotherapeutic drugs into cancer cells with a capability of real-time monitoring of drug release.

Intertumoral and intratumoral barriers as approaches for drug delivery and theranostics to solid tumors using stimuli-responsive materials.

The solid tumors provide a series of biological barriers in cellular microenvironment for designing drug delivery methods based on advanced stimuli-responsive materials. These intertumoral and intratumoral barriers consist of perforated endotheliums, tumor cell crowding, vascularity, lymphatic drainage blocking effect, extracellular matrix (ECM) proteins, hypoxia, and acidosis. Triggering opportunities have been drawn for solid tumor therapies based on single and dual stimuli-responsive drug delivery systems (DDSs) that not only improved drug targeting in deeper sites of the tumor microenvironments, but also facilitated the antitumor drug release efficiency. Single and dual stimuli-responsive materials which are known for their lowest side effects can be categorized in 17 main groups which involve to internal and external stimuli anticancer drug carriers in proportion to microenvironments of targeted solid tumors. Development of such drug carriers can circumvent barriers in clinical trial studies based on their superior capabilities in penetrating into more inaccessible sites of the tumor tissues. In recent designs, key characteristics of these DDSs such as fast response to intracellular and extracellular factors, effective cytotoxicity with minimum side effect, efficient permeability, and rate and location of drug release have been discussed as core concerns of designing paradigms of these materials.

Matrix metalloproteinase-responsive hydrogels with tunable retention for on-demand therapy of inflammatory bowel disease

Therapeutic options for addressing inflammatory bowel disease (IBD) include the administration of an enema to reduce intestinal inflammation and alleviate associated symptoms. However, uncontrollable retention of enemas in the intestinal tract has posed a long-term challenge for improving their therapeutic efficacy and safety. Herein we have developed a protease-labile hydrogel system as an on-demand enema vehicle with tunable degradation and drug release rates in response to varying matrix metalloproteinase-9 (MMP-9) expression. The system, composed of three tailored hydrogel networks, is crosslinked by poly (ethylene glycol) (PEG) with 2-, 4- and 8-arms through dynamic hydrazone bonds to confer injectability and generate varying network connectivity. The retention time of the hydrogels can be tuned from 12 to 36 h in the intestine due to their different degradation behaviors induced by MMP-9. The drug-releasing rate of the hydrogels can be controlled from 0.0003 mg/h to 0.278 mg/h. In addition, injection of such hydrogels in vivo resulted in significant differences in therapeutic effects including MMP-9 consumption, colon tissue repair, reduced collagen deposition, and decreased macrophage cells, for treating a mouse model of acute colitis. Among them, GP-8/5-ASA exhibits the best performance. This study validates the effectiveness of the tailored design of hydrogel architecture in response to pathological microenvironment cues, representing a promising strategy for on-demand therapy of IBD. Statement of significanceThe uncontrollable retention of enemas at the delivery site poses a long-term challenge for improving therapeutic efficacy in IBD patients. MMP-9 is highly expressed in IBD and correlates with disease severity. Therefore, an MMP-9-responsive GP hydrogel system was developed as an enema by linking multi-armed PEG and gelatin through hydrazone bonds. This forms a dynamic hydrogel characterized by in situ gelation, injectability, enhanced bio-adhesion, biocompatibility, controlled retention time, and regulated drug release. GP hydrogels encapsulating 5-ASA significantly improved the intestinal phenotype of acute IBD and demonstrated notable therapeutic differences with increasing PEG arms. This method represents a promising on-demand IBD therapy strategy and provides insights into treating diseases of varying severities using endogenous stimulus-responsive drug delivery systems.

Intelligent Systems based on Cyclodextrins for the Treatment of Breast Cancer.

The incidence of breast cancer has been increasing over the last four decades, although the mortality rate has decreased. Endocrine therapy and chemotherapy are the most used options for cancer treatment but several obstacles are still attributed to these therapies. Smart materials, such as nanocarriers for targeting, delivery and release of active ingredients, sensitive to intrinsic-stimuli (pH-responsive, redox-responsive, enzyme- responsive, and thermo-responsive) and extrinsic-stimuli (ultrasound-responsive, magnetic-responsive, light-responsive) have been studied as a novel strategy in breast cancer therapy. Cyclodextrins (CDs) are used in the design of these stimuli-responsive drug carrier and delivery systems, either through inclusion complexes with hydrophobic molecules or covalent bonds with large structures to generate new materials. The present work aims to gather and integrate recent data from in vitro and in vivo preclinical studies of CD-based stimuli- responsive systems to contribute to the research in treating breast cancer. All drug carriers showed high in vitro release rates in the presence of a stimulus. The stimuli-responsive nanoplatforms presented biocompatibility and satisfactory results of IC50, inhibition of cell viability and antitumor activity against several breast cancer cell lines. Additionally, these systems led to a significant reduction in drug dosages, which encouraged possible clinical studies for better alternatives to traditional antitumor therapies.

Stimuli-responsive drug delivery system for breast cancer treatment

In the annals of cancer treatment within the domain of nanomedicine, the utilization of stimulus-response drug delivery systems has emerged as a focal point of considerable significance. While a multitude of diverse methodologies are presently employed for the treatment of tumors, the preeminent and most efficacious approach, particularly in the context of intricate scenarios, pertains to the targeted administration of therapeutic and diagnostic nanoparticles into the tumor milieu. These nanoparticles exhibit the inherent potential to acclimatize to the nuanced microenvironment of the tumor, thereby surmounting the challenges posed by tumor heterogeneity. The stimuli-responsive attributes inherent to nanoscale particles can broadly be delineated into two distinct categories: endogenous and exogenous, with a minority manifesting characteristics of both classifications. This scientific review provides an overview of the discourse surrounding exogenous drug delivery systems, which leverage ultrasound and magnetic fields as responsive stimuli, alongside endogenous drug delivery systems employing pH variations and enzymatic cues as triggering mechanisms. The findings of this review emphasize the significance of stimuli-responsive drug delivery systems as a promising strategy to enhance the specificity and efficacy within the sphere of breast cancer treatment. Finally, the review concludes with a discussion on the future directions and potential clinical applications of these systems.

In-situ forming Cu-based metal-organic framework in the presence of chitosan-Fe3O4 nanohybrids: A pH-sensitive carrier for controlled release of doxorubicin

In recent years, stimuli-responsive drug delivery systems based on pH, particularly those developed using bio-derived nanocomposite systems, have gained significant attention. In this work, a novel magnetic carrier was designed based on biopolymeric chitosan and metal-organic framework (MOF) for pH-controlling the release of anticancer drugs. To end this, an in-situ green method was performed to form Cu-based MOF in the presence of a magnetic polysaccharide synthesized by precipitation method toward the construction of CS/Fe3O4/Cu-MOF nanocomposite. The nanocomposite was immersed in an aqueous solution of a model anticancer drug, doxorubicin (DOX), and a higher loading capacity (90.1 ± 0.5 %) was achieved. The in-vitro drug release study showed low release rates in simulated physiological environments (pH 7.4, 37 °C, lower than about 20 %), but higher release rates in tumor tissue conditions (pH 4.5, 41 °C, higher than about 60 %) over 96 h, allowing for sustained and extended delivery of DOX. Additionally, the MTT assay demonstrated that the blank and DOX-loaded CS/Fe3O4/Cu-MOF had good cytocompatibility (over 80 % cell viability) and considerable cytotoxicity (lower than 40 % at 16 μg/mL) toward breast cancer (MCF-7) cell line, respectively. These results indicated that the synthesized nanocomposite with suitable pH-sensitivity has potential as a targeted anticancer agent.

Recent Progress in Multifunctional Stimuli-Responsive Combinational Drug Delivery Systems for the Treatment of Biofilm-Forming Bacterial Infections.

Drug-resistant infectious diseases pose a substantial challenge and threat to medical regimens. While adaptive laboratory evolution provides foresight for encountering such situations, it has inherent limitations. Novel drug delivery systems (DDSs) have garnered attention for overcoming these hurdles. Multi-stimuli responsive DDSs are particularly effective due to their reduced background leakage and targeted drug delivery to specific host sites for pathogen elimination. Bacterial infections create an acidic state in the microenvironment (pH: 5.0-5.5), which differs from normal physiological conditions (pH: 7.4). Infected areas are characterized by the overexpression of hyaluronidase, gelatinase, phospholipase, and other virulence factors. Consequently, several effective stimuli-responsive DDSs have been developed to target bacterial pathogens. Additionally, biofilms, structured communities of bacteria encased in a self-produced polymeric matrix, pose a significant challenge by conferring resistance to conventional antimicrobial treatments. Recent advancements in nano-drug delivery systems (nDDSs) show promise in enhancing antimicrobial efficacy by improving drug absorption and targeting within the biofilm matrix. nDDSs can deliver antimicrobials directly to the biofilm, facilitating more effective eradication of these resilient bacterial communities. Herein, this review examines challenges in DDS development, focusing on enhancing antibacterial activity and eradicating biofilms without adverse effects. Furthermore, advances in immune system modulation and photothermal therapy are discussed as future directions for the treatment of bacterial diseases.

Designing Dual-Responsive Drug Delivery Systems: The Role of Phase Change Materials and Metal-Organic Frameworks.

Stimuli-responsive drug delivery systems (DDSs) offer precise control over drug release, enhancing therapeutic efficacy and minimizing side effects. This review focuses on DDSs that leverage the unique capabilities of phase change materials (PCMs) and metal-organic frameworks (MOFs) to achieve controlled drug release in response to pH and temperature changes. Specifically, this review highlights the use of a combination of lauric and stearic acids as PCMs that melt slightly above body temperature, providing a thermally responsive mechanism for drug release. Additionally, this review delves into the properties of zeolitic imidazolate framework-8 (ZIF-8), a stable MOF under physiological conditions that decomposes in acidic environments, thus offering pH-sensitive drug release capabilities. The integration of these materials enables the fabrication of complex structures that encapsulate drugs within ZIF-8 or are enveloped by PCM layers, ensuring that drug release is tightly controlled by either temperature or pH levels, or both. This review provides comprehensive insights into the core design principles, material selections, and potential biomedical applications of dual-stimuli responsive DDSs, highlighting the future directions and challenges in this innovative field.

NATURALLY OCCURRING SWELLABLE POLYSACCHARIDES-BASED STIMULI-RESPONSIVE SMART TABLETS – A NEW WINDOW OF OPPORTUNITY

Currently, synthetic and semi-synthetic polymers are widely used in the development of various drug delivery systems (DDSs), biomedical and surgical devices, and healthcare materials. However, many drawbacks and problems are associated with these polymeric materials, including toxicity, immunogenicity, non-biodegradability, non-biocompatibility, and complicated, costly synthesis. To address such drawbacks, nowadays, naturally occurring swellable polysaccharides (NOSPs) are being evaluated for the possible replacement of synthetic polymers. NOSPs have shown remarkable stimuli-responsive properties, which made them an ideal material to develop stimuli-responsive DDSs, especially “smart tablets”. The present review focuses on the summarization of stimuli-responsive properties (swelling, on-off switching, and drug release) of smart/stimuli-responsive tablets that respond to various stimuli, e.g., pH, solvent, transit, time, etc. This article highlights the need to develop NOSPs-based smart tablets for intelligent and targeted drug delivery.

Stimuli-sensitive biomimetic nanoparticles for the inhibition of breast cancer recurrence and pulmonary metastasis

Biomimetic nanoparticles represent a promising avenue for mitigating rapid clearance by the reticuloendothelial system (RES); however, current challenges include insufficient tumour targeting, suboptimal adhesion, and inadequate localized drug release within tumour regions. These shortcomings contribute to persistent contests, such as recurrence and pulmonary metastasis, even with advanced breast cancer therapies. Stimuli-sensitive drug release can furbish the membrane coated nanoparticles for their efficiency against the stated problems. To enhance the efficacy of biomimetic nanoparticles in addressing these issues, we proposed a versatile, stimuli-responsive drug delivery system by encapsulating doxorubicin (Dox) and perfluorohexane (PFH) within poly (lactic-co-glycolic acid) (PLGA) nanoparticles, subsequently coated with macrophage-derived cell membranes. Within this framework, PFH serves as the mediator for ultrasonic (US)-irradiation-triggered drug release specifically within tumour microenvironment, while the macrophage-derived cell membrane coating enhances cell adhesion, enables immune evasion, and natural tumour-homing ability. The characterization assays and in vitro evaluations yielded encouraging results, indicating enhanced targeting and release efficiencies. In vivo studies demonstrated marked inhibitory effects on both breast cancer recurrence and pulmonary metastasis. The resulting data indicate that these engineered nanoparticles have notable potential for targeted delivery and controlled release upon US irradiation, thereby offering significant therapeutic efficacy against primary breast cancer, pulmonary metastasis, and recurrent malignancies. Our findings lay the groundwork for a novel clinical approach, representing an intriguing direction for ongoing investigation by oncologists.

Aptamer-Based Smart Targeting and Spatial Trigger-Response Drug-Delivery Systems for Anticancer Therapy.

In recent years, the field of drug delivery has witnessed remarkable progress, driven by the quest for more effective and precise therapeutic interventions. Among the myriad strategies employed, the integration of aptamers as targeting moieties and stimuli-responsive systems has emerged as a promising avenue, particularly in the context of anticancer therapy. This review explores cutting-edge advancements in targeted drug-delivery systems, focusing on the integration of aptamers and stimuli-responsive platforms for enhanced spatial anticancer therapy. In the aptamer-based drug-delivery systems, we delve into the versatile applications of aptamers, examining their conjugation with gold, silica, and carbon materials. The synergistic interplay between aptamers and these materials is discussed, emphasizing their potential in achieving precise and targeted drug delivery. Additionally, we explore stimuli-responsive drug-delivery systems with an emphasis on spatial anticancer therapy. Tumor microenvironment-responsive nanoparticles are elucidated, and their capacity to exploit the dynamic conditions within cancerous tissues for controlled drug release is detailed. External stimuli-responsive strategies, including ultrasound-mediated, photo-responsive, and magnetic-guided drug-delivery systems, are examined for their role in achieving synergistic anticancer effects. This review integrates diverse approaches in the quest for precision medicine, showcasing the potential of aptamers and stimuli-responsive systems to revolutionize drug-delivery strategies for enhanced anticancer therapy.

Polyacrylic acid/polyvinylpyrrolidone/iron oxide nanocarrier for efficient delivery of doxorubicin

Recently, stimuli-responsive drug delivery systems (DDS), especially pH-responsive ones, have drawn a lot of attention to overcome the unfavourable side effects of traditional cancer treatments. In this work, a nanocomposite hydrogel based on polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), and iron oxide (hematite, Fe2O3) nanoparticles was developed using the water/oil/water emulsification technique for the efficient delivery of doxorubicin (DOX) drug. The synthesized nanocarrier was characterized via XRD, and FT-IR to get information about its crystalline structure and the interaction between the functional groups of the different constituents, respectively. Its size distribution and colloidal stability were investigated via DLS and zeta potential tests, and morphological study was carried out by FE-SEM. The nanoparticles were found to be uniform and monodisperse, with an average size of 319 nm and a surface charge of −30.4 mV. The incorporation of hematite increased the drug loading (48.5 %) and encapsulation efficiency (86.57 %) due to its high porosity and surface area. Drug release was tested at pH 7.4 and 5.4, corresponding to healthy and cancerous tissues, and the results demonstrated the pH responsiveness of the system, with faster release (54 % in 24 h) in the acid medium. MTT and flow cytometry tests corroborated its strong anticancer effect since the nano-platform significantly reduced the survival rate of cancer cells. The designed pH-responsive platform holds great potential for breast cancer therapy.

A stimulus responsive microneedle-based drug delivery system for cancer therapy.

The intricate nature of the tumor microenvironment (TME) results in the inefficient delivery of anticancer drugs within tumor tissues, significantly compromising the therapeutic effect of cancer treatment. To address this issue, transdermal drug delivery microneedles (MNs) with high mechanical strength have emerged. Such MNs penetrate the skin barrier, enabling efficient drug delivery to tumor tissues. This approach enhances drug bioavailability, while also mitigating concerns such as liver and kidney toxicity associated with intravenous and oral drug administration. Notably, stimulus responsive MNs designed for drug delivery have the capacity to respond to various biological signals and pathological changes. This adaptability enables them to exert therapeutic effects within the TME, exploiting biochemical variations and tailoring treatment strategies to suit tumor characteristics. The present review surveys recent advancements in responsive MN systems. This comprehensive analysis serves as a valuable reference for the prospective application of smart MN drug delivery systems in cancer therapy.

Unveiling innovative therapeutic strategies and future trajectories on stimuli-responsive drug delivery systems for targeted treatment of breast carcinoma.

This comprehensive review delineates the latest advancements in stimuli-responsive drug delivery systems engineered for the targeted treatment of breast carcinoma. The manuscript commences by introducing mammary carcinoma and the current therapeutic methodologies, underscoring the urgency for innovative therapeutic strategies. Subsequently, it elucidates the logic behind the employment of stimuli-responsive drug delivery systems, which promise targeted drug administration and the minimization of adverse reactions. The review proffers an in-depth analysis of diverse types of stimuli-responsive systems, including thermoresponsive, pH-responsive, and enzyme-responsive nanocarriers. The paramount importance of material choice, biocompatibility, and drug loading strategies in the design of these systems is accentuated. The review explores characterization methodologies for stimuli-responsive nanocarriers and probes preclinical evaluations of their efficacy, toxicity, pharmacokinetics, and biodistribution in mammary carcinoma models. Clinical applications of stimuli-responsive systems, ongoing clinical trials, the potential of combination therapies, and the utility of multifunctional nanocarriers for the co-delivery of assorted drugs and therapies are also discussed. The manuscript addresses the persistent challenge of drug resistance in mammary carcinoma and the potential of stimuli-responsive systems in surmounting it. Regulatory and safety considerations, including FDA guidelines and biocompatibility assessments, are outlined. The review concludes by spotlighting future trajectories and emergent technologies in stimuli-responsive drug delivery, focusing on pioneering approaches, advancements in nanotechnology, and personalized medicine considerations. This review aims to serve as a valuable compendium for researchers and clinicians interested in the development of efficacious and safe stimuli-responsive drug delivery systems for the treatment of breast carcinoma.

Glucose-Responsive Self-Regulated Injectable Silk Fibroin Hydrogel for Controlled Insulin Delivery.

Stimuli-responsive drug delivery systems are gaining importance in personalized medicine to deliver therapeutic doses in response to disease-specific stimulation. Pancreas-mimicking glucose-responsive insulin delivery systems offer improved therapeutic outcomes in the treatment of type 1 and advanced stage of type 2 diabetic conditions. Herein, we present a glucose-responsive smart hydrogel platform based on phenylboronic acid-functionalized natural silk fibroin protein for regulated insulin delivery. The modified protein was synergistically self-assembled and cross-linked through β-sheet and phenylboronate ester formation. The dynamic nature of the bonding confers smooth injectability through the needle. The cross-linked hydrogel structures firmly hold the glucose-sensing element and insulin in its pores and contribute to long-term sensing and drug storage. Under hyperglycemic conditions, the hydrogen peroxide generated from the sensing element induces hydrogel matrix degradation by oxidative cleavage, enabling insulin release. In vivo studies in a type 1 diabetic Wistar rat model revealed that the controlled insulin release from the hydrogel restored diabetic glucose level to physiological conditions for 36 h. This work establishes the functional modification of silk fibroin into a glucose-responsive hydrogel platform for regulated and functional insulin delivery application.