Smart Drug Carriers Research Articles

Versatile hydrogel drug carrier loading with peptide-carbon dots conjugates for efficient targeting and synergistic suppression of breast cancer cell

Breast cancer become the most prevalent malignancy and is rising up to the first leading cause of cancer-related mortality among the female people globally. Approaches for safe, specific targeting and efficient inhibition of breast cancer cells, are urgently demanded for lifting the survival rate of breast tumor-bearing patients. Herein, a versatile hydrogel drug carrier consisting of doxorubicin (DOX)-loaded hydrogel microsphere and carbon dots (CDs)-loaded peptide nanowires (DOX@PEG/PNFs-CDs) was constructed, presenting specific targeting and synergistic anti-cancer cell potencies. The hydrogel PEG microspheres with a rich porous structure benefited the drug loading efficiency, demonstrating good biodegradability and higher drug release efficiency at acidic environment. Benefiting from the RGD group of the peptide nanowires, the drug-loaded system specific targeted onto the MDA-MB-231 cells, subsequently promoting the synergistic inhibition of the cancer cell growth by DOX and metformin derived CDs. This all-in-one smart drug carrier post a promising strategy for breast cancer treatment.

Impact of Artificial Intelligence on Drug Development and Delivery.

This review explores the transformative impact of AI on drug development and delivery in pharmaceutical sciences, spanning formulation design, real-time monitoring, targeted delivery, and future prospects. The rational design of smart drug carriers, such as AI-optimized liposomes for cancer therapy, optimizes formulations for individual patient needs. AI-driven sensors, exemplified by glucose-monitoring biosensors for diabetics, enable adaptive drug administration, enhancing precision. Despite promises, challenges like biocompatibility, regulations, and ethics persist. Interdisciplinary collaboration and transparent communication are crucial for responsible AI adoption. Anticipated trends include personalized dosage optimization and intelligent nanocarriers. The review underscores AI's potential in reshaping pharmaceuticals for patient-centric care while addressing challenges for widespread adoption.

Enhancement of antimicrobial and antibiofilm activities of liposomal fatty acids

Microbial biofilms are protected surface-attached communities of bacteria or fungi with high drug tolerance that typically cause persistent infections. Smart drug carriers are being explored as a promising platform of antimicrobials to address their recalcitrance to antibiotic agents and minimize the side effects of current therapies. In this study, soy lecithin liposomes loaded with lauric acid (LA) and myristoleic acid (MA) were formulated using an emulsification method, and their antibiofilm properties were evaluated. The physio-chemical properties of the most potent liposome were characterized using a zeta sizer, transmission electron microscopy (TEM), fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. TEM and zeta sizer analysis of the liposome revealed a homogeneous spherical structure with an average size of 159.2 nm and zeta potential of − 5.4 mV. The unilamellar liposomes loaded with LA at 0.1–0.5 µg/mL achieved obvious antibiofilm efficiency against Staphylococcus aureus and Candida albicans and their dual biofilms. Also, LA-loaded liposome formulation efficiently disrupted preformed biofilms of S. aureus and C. albicans. Furthermore, formulated liposomal LA (0.1 µg/mL) exhibited 100-fold increased dual biofilm inhibition compared to LA alone. The single biofilms and dual biofilm formation on polystyrene were reduced as determined by 3D-bright field and scanning electron microscopy. Zeta potential measurements exhibited neutralized surface charge of S. aureus, and the liposomes inhibited hyphae formation in C. albicans. These findings demonstrated that the LA-incorporated liposomes have great potential to become a new, effective, and good antibiofilm agent for treating S. aureus and C. albicans infections.

Continuous-Flow Nanoprecipitation Method to Synthesize Degradable Hollow Mesoporous Organosilica Nanoparticles for Insecticide Delivery.

Degradable mesoporous organosilica nanoparticles (MONPs) are attracting significant attention in the area of designing smart drug carriers mainly due to their excellent stability and multiple functions. However, the efficient, controllable, and large-scale production of MONPs still faces huge challenges. Herein, a novel and facile continuous-flow nanoprecipitation strategy was reported to synthesize hollow MONPs with highly uniform and tailored properties. The synthesized hollow MONPs possessed a large surface area (SBET > 1070.1 m2 g-1), narrow size distribution, large hollow cavity, and thin shell. Interestingly, the incorporation of organic moieties into silica cross-linked networks led to the timely degradation of nanocarriers with the desired responsiveness. Moreover, the applicability of the as-obtained hollow MONPs has been demonstrated in the loading and pH-responsive release of thiamethoxam (THI). The resultant THI-loaded MONPs possessed long-term storage stability at a low temperature and showed release behaviors in response to a basic environment. Benefiting from the shielding property of MONPs, THI-loaded MONPs manifested superior stability against the photolysis as compared to that of the THI technical. This work provides a new consideration for promoting the advancement of nanotechnology in agricultural fields.

Recent Advances Ultra-Porous Drug Nano-Carriers: Synthesis and Targeting Approaches

Mesoporous silica has attracted increasing interest due to the pandemic spreading of the viral infection in recent years. These smart materials have many advantages as high loading capacity, high surface area, and unique morphology making them great materials for smart drug carriers. In this review, I summarized the synthesis of Ultra-Porous Drug Nano-Carriers in recent years. Factors affecting (mesoporous nanoparticles) MSN Synthesis as surfactants, Co-surfactants, and solvents were mentioned in the full description and targeting approaches. Types of silica nanoparticles such as Mesoporous SBA-1 silicas, Mesoporous SBA-2 silicas, and hybrid mesoporous materials are also shown in a detailed manner. Future research efforts are also highlighted for AI-based techniques aimed at more accurate tissue engineering prediction and operation optimization in drug carrier-based processes.

Fabrication of triple-crosslinked gelatin/alginate hydrogels for controlled release applications

Hydrogels have been demonstrated as smart drug carriers to recognize the tumor microenvironment for cancer treatment, where the dynamic crosslinks in the hydrogel network contribute to the stimuli-responsive features but also result in poor stability and weak mechanical property of the hydrogels. Here, phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG) was synthesized to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds, and then calcium ions (Ca2+) were added to introduce the third calcium-carboxylate crosslinking in the network to form the triple-crosslinked PPG/ADA-Ca2+ hydrogels. Given the three types of dynamic bonds in the network, PPG/ADA-Ca2+ hydrogels possessed a self-healing manner, stimuli-responsiveness, and better mechanical properties compared to single- or double-crosslinked hydrogels. The controlled release capability of PPG/ADA-Ca2+ hydrogels was also demonstrated, showing the encapsulated molecules can be rapidly released from the hydrogel network in the presence of hydrogen peroxide while the release rate can be slowed down at acidic pH. Furthermore, PPG/ADA-Ca2+ hydrogels presented selected cytotoxicity and drug delivery to cancer cells due to the regulated degradation by the cellular microenvironment. Taken together, PPG/ADA-Ca2+ hydrogels have been demonstrated as promising biomaterials with multiple desirable properties and dynamic features to perform controlled molecule release for biomedical applications.

Synthesis of Microparticles with Diverse Thermally Responsive Shapes Originated from the Same Janus Liquid Crystalline Microdroplets.

Liquid crystalline elastomer (LCE)-based microparticles that can change shapes in response to external stimuli are of great interest for potential applications such as artificial cells, micro-actuators, micro-valves, and smart drug carriers. Here, the synthesis of LCE microparticles with diverse temperature-dependent anisotropic shapes originated from the same Janus microdroplets is reported. The Janus microdroplets, suspended in an aqueous solution of surfactants, are transformed from microdroplets consisting of a mixture of liquid crystal (LC) monomers, oligomers, silicone oil, and an organic solvent, after the removal of the organic solvent. The molecular alignment of the LC part at the interface, whether planar, homeotropic, or hybrid, is dependent on the choice of the surfactants but not affected by the silicone oil. After polymerization and solvent extraction of the unreacted components, LCE microparticles of various shapes are obtained depending on the concentration and composition of the surfactants, the weight ratio of the LC part to the silicone oil part, and the choice of the extraction solvent. The microparticles that undergo different synthetic pathways show distinct thermally responsive shapes, much like how stem cells differentiate in different environmental conditions.

Response and Regulation of the Microenvironment Based on Hollow Structured Drug Delivery Systems

AbstractHollow structured materials with easily modifiable surfaces and enclosed interior spaces have emerged as the most promising candidates in drug delivery systems (DDS). With various functional components and inspiring cavities for creative reinvention, the response and regulation of the external and internal microenvironment of hollow structures enable their ideal drug delivery capabilities by improving drug aggregation in targeted sites and maintaining plasma concentrations at the optimal therapeutic ranges. This review begins with an in‐depth explanation of the interactions and release mechanisms of hollow structure‐based DDS, including diffusion, assembly, solvent activation, and chemical control, all of which are of great significance for the design of smart drug carriers. Next, recent advances in external microenvironment‐responsive drug delivery systems are introduced, based on various chemical signals and external field assists. Focusing on the unique view of intra‐carrier variability, the strategies for regulating the internal environment are then highlighted, including pH regulation, temperature regulation, and mechanical force regulation. Finally, this review discusses possible challenges and prospects for hollow structure‐based, particularly hollow multishelled structures intelligence‐responsive drug delivery platforms, providing valuable strategies for the development of the next generation of responsive DDS.

Cover Image, Volume 61, Issue 7

Journal of Polymer ScienceVolume 61, Issue 7 p. i-i COVER IMAGEFree Access Cover Image, Volume 61, Issue 7 First published: 01 April 2023 https://doi.org/10.1002/pol.20230146AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract Stimuli-responsive materials have significant potential to develop advanced drug delivery systems. Near-infrared light (NIR)-activated smart drug carriers could enhance drug release on demand. The fabricated core-shell electrospun nanofibrous materials are easily activable using NIR light as an external stimulus. The smart behavior is due to the decoration of the platform with photoactive plasmonic nanoparticles. The hierarchically structured nanoplatform accelerates the drug's release upon NIR irradiation and sheds new light on the future applications of smart drug delivery systems. Details are found in the article on page 521 from Filippo Pierini and colleagues. (DOI: 10.1002/pol.20220747) Volume61, Issue71 April 2023Pages i-i RelatedInformation

Bacterial Membrane Vesicles as Smart Drug Delivery and Carrier Systems: A New Nanosystems Tool for Current Anticancer and Antimicrobial Therapy.

Bacterial membrane vesicles (BMVs) are known to be critical communication tools in several pathophysiological processes between bacteria and host cells. Given this situation, BMVs for transporting and delivering exogenous therapeutic cargoes have been inspiring as promising platforms for developing smart drug delivery systems (SDDSs). In the first section of this review paper, starting with an introduction to pharmaceutical technology and nanotechnology, we delve into the design and classification of SDDSs. We discuss the characteristics of BMVs including their size, shape, charge, effective production and purification techniques, and the different methods used for cargo loading and drug encapsulation. We also shed light on the drug release mechanism, the design of BMVs as smart carriers, and recent remarkable findings on the potential of BMVs for anticancer and antimicrobial therapy. Furthermore, this review covers the safety of BMVs and the challenges that need to be overcome for clinical use. Finally, we discuss the recent advancements and prospects for BMVs as SDDSs and highlight their potential in revolutionizing the fields of nanomedicine and drug delivery. In conclusion, this review paper aims to provide a comprehensive overview of the state-of-the-art field of BMVs as SDDSs, encompassing their design, composition, fabrication, purification, and characterization, as well as the various strategies used for targeted delivery. Considering this information, the aim of this review is to provide researchers in the field with a comprehensive understanding of the current state of BMVs as SDDSs, enabling them to identify critical gaps and formulate new hypotheses to accelerate the progress of the field.

Real-time monitoring of NIR-triggered drug release from phase-changeable nanodroplets by photoacoustic/ultrasound imaging

Optical-responsive nanodroplets have recently been studied as a new mode of remotely controlled drug delivery. As a class of new emerging smart drug carriers, NIR-absorber-loaded perfluorocarbon nanodroplets can be converted into gas bubbles through laser stimulation, called optical droplet vaporization (ODV), which provides a potential strategy to deliver therapeutic agents to solid tumors on demand. However, there is a lack of suitable technologies to monitor these drug-loaded nanodroplet behaviors in vivo, and control the site and amount of drug released. In this study, ultrasound and photoacoustic imaging technology were applied to directly monitor optical-responsive, drug-loaded nanodroplets within the tissue. We explored the effects of laser energy, repetition rate, and number of pulses on the release profiles of the delivered drug as well as ultrasound and photoacoustic imaging signal-intensity curves. The conducted studies demonstrated that this noninvasive technology helped determine the optimum time point for laser activation on accumulated drug-loaded nanodroplets within tissues, allowing for the potential to effectively treat pathologies while minimizing drug-related toxicities.

Smart delivery systems for microbial biofilm therapy: Dissecting design, drug release and toxicological features.

Bacterial biofilms are highly protected surface attached communities of bacteria that typically cause chronic infections. To address their recalcitrance to antibiotics and minimise side effects of current therapies, smart drug carriers are being explored as promising platforms for antimicrobials. Herein, we briefly summarize recent efforts and considerations that have been applied in the design of these smart carriers. We guide readers on a journey on how they can leverage the inherent biofilm microenvironment, external stimuli, or combine both types of stimuli in a predictable manner. The specific carrier features that are responsible for their 'on-demand' properties are detailed and their impact on antibiofilm property are further discussed. Moreover, an analysis on the impact of such features on drug release profiles is provided. Since nanotechnology represents a significant slice of the drug delivery cake, some insights on the potential toxicity are also depicted. We hope that this review inspires researchers to use their knowledge and creativity to design responsive systems that can eradicate biofilm infections.

Electro-stimulated drug release by methacrylated hyaluronic acid-based conductive hydrogel with enhanced mechanical properties

Recently, the design of stimuli-responsive hydrogels for controlled drug delivery systems has been extensively investigated to meet therapeutic needs and optimize the release pattern of the drug. Being a natural polyelectrolyte, hyaluronic acid (HA) is excellent potential to generate new opportunities for electro-responsive drug carrier applications. In the current study, HA-based electroconductive hydrogel was developed as a novel smart drug carrier for anti-inflammatory drug release by the combination of in-situ and post polymerization mechanisms. HA was modified through methacrylation reaction to introduce photocrosslinkable groups into its structure and then reduced graphene oxide (rGO) was encapsulated into methacrylated HA (HA/MA) hydrogel by using the photopolymerization technique. In the post polymerization process, polyaniline (PANI) was incorporated/loaded into HA/MA-rGO polymeric network produced in previous step. The produced HA/MA-rGO-PANI hydrogel exhibited sufficient electrical conductivity providing the desirable electro-responsive ability for Ibuprofen (IBU) release. Furthermore, it has superior mechanical performance compared to pure (HA/MA) and rGO containing (HA/MA-rGO) hydrogels. IBU release from the hydrogel was successfully triggered by electrical stimulation and the cumulative drug release also enhanced by increasing of the applied voltage. These results highlighted that the novel HA/MA-rGO-PANI hydrogel could be a promising candidate for electrical-stimulated anti-inflammatory release systems in neural implant applications.

Organically surface engineered mesoporous silica nanoparticles control the release of quercetin by pH stimuli

Controlling the premature release of hydrophobic drugs like quercetin over physiological conditions remains a challenge motivating the development of smart and responsive drug carriers in recent years. This present work reported a surface modification of mesoporous silica nanoparticles (MSN) by a functional compound having both amines (as a positively charged group) and carboxylic (negatively charged group), namely 4-((2-aminoethyl)amino)-4-oxobut-2-enoic acid (AmEA) prepared via simple mechanochemistry approach. The impact of MSN surface modification on physical, textural, and morphological features was evaluated by TGA, N2 adsorption–desorption, PSA-zeta, SEM, and TEM. The BET surface area of AmEA-modified MSN (MSN-AmEA) was found to be 858.41 m2 g−1 with a pore size of 2.69 nm which could accommodate a high concentration of quercetin 118% higher than MSN. In addition, the colloidal stability of MSN-AmEA was greatly improved as indicated by high zeta potential especially at pH 4 compared to MSN. In contrast to MSN, MSN-AmEA has better in controlling quercetin release triggered by pH, thanks to the presence of the functional groups that have a pose-sensitive interaction hence it may fully control the quercetin release, as elaborated by the DFT study. Therefore, the controlled release of quercetin over MSN-AmEA verified its capability of acting as a smart drug delivery system.

Biodegradable Redox-Responsive AIEgen-Based-Covalent Organic Framework Nanocarriers for Long-Term Treatment of Myocardial Ischemia/Reperfusion Injury.

Timely restoration of blood supply after myocardial ischemia is imperative for the treatment of acute myocardial infarction but causes additional myocardial ischemia/reperfusion (MI/R) injury, which has not been hitherto effectively targeted by interventions for MI/R injury. Hence, the development of advanced nanomedicine that can reduce apoptosis of cardiomyocytes while protecting against MI/R in vivo is of utmost importance. Herein, a redox-responsive and emissive TPE-ss covalent organic framework (COF) nanocarrier by integrating aggregation-induced emission luminogens and redox-responsive disulfide motifs into the COF skeleton is developed. TPE-ss COF allows for efficient loading and delivery of matrine, a renowned anti-cryptosporidial drug, which significantly reduces MI/R-induced functional deterioration and cardiomyocyte injury when injected through the tail vein into MI/R models at 5min after 30min of ischemia. Moreover, TPE-ss COF@Matrine shows a drastic reduction in cardiomyocyte apoptosis and improvements in cardiac function and survival rate. The effect of the TPE-ss COF carrier is further elucidated by enhanced cardiomyocyte viability and triphenyltetrazolium chloride staining in vitro. This work demonstrates the cardioprotective effect of TPE-ss COFs for MI/R injury, which unleashes the immense potential of using COFs as smart drug carriers for the peri-reperfusion treatment of ischemic heart disease with low cost, high stability, and single postoperative intervention.

First-principles investigation of Hydroxycarbamide anticancer drug delivery by X12N12 (X = B, Al, Ga) fullerene nanostructures: A DFT, NBO and QTAIM analysis

The group-III nitride fullerenes (B12N12, Al12N12 and Ga12N12) are noncytotoxic and chemically stabile for human and are the perfect carriers for the delivery of drugs. This present study has computed the the different properties to explore the interaction among Hydroxycarbamide (HU) and X12N12 (B12N12, Al12N12 and Ga12N12) nanocages using DFT method both in gas and water phase. Our investigation exhibits that Al12N12 and Ga12N12 can be smart drug carrier for the delivery of HU drug as confirmation from the adsorption study. The energy of adsorption of all the complexes shows chemisorption type adsorption, indicating the interaction between the HU and Al12N12 and Ga12N12. The change of Eg of our studied structures indicates the sensitivity of the nanocages towards HU drug molecule. Therefore, it is predicted that HU drug onto the Al12N12 and Ga12N12 nanocages might be good delivery vehicle which will be helpful to which will benefit from saving human.

PEG-Functionalized Hollow Multishelled Structures with On-Off Switch and Rate-Regulation for Controllable Antimicrobial Release.

The construction of responsive antimicrobial carriers with multifunctional and controllable release is an attractive but challenging proposition. Recently developed hollow multishelled structures (HoMSs) offers structural advantages, such as easily modifiable surfaces and mutually influenced shells. Herein, we report a novel pH-responsive antimicrobial carrier having hierarchical shells as multilevel responsive bodies using polyethylene glycol (PEG) as a gated regulator. The interaction between PEG-functionalized shells endows them with a pH-responsive switch and rate-regulator capability. These features are present in the form of rapid release of molecules wrapped in the outer shell, and controlled diffusion of antimicrobials stored in the inner shell by electrostatic interaction, resulting in a long-lasting mildew resistance for up to 71 days. The versatility of the hierarchical interactions of HoMSs will inspire the design of promising smart drug carriers.

PEG‐Functionalized Hollow Multishelled Structures with On‐Off Switch and Rate‐Regulation for Controllable Antimicrobial Release

The construction of responsive antimicrobial carriers with multifunctional and controllable release is an attractive but challenging proposition. Recently developed hollow multishelled structures (HoMSs) offers structural advantages, such as easily modifiable surfaces and mutually influenced shells. Herein, we report a novel pH-responsive antimicrobial carrier having hierarchical shells as multilevel responsive bodies using polyethylene glycol (PEG) as a gated regulator. The interaction between PEG-functionalized shells endows them with a pH-responsive switch and rate-regulator capability. These features are present in the form of rapid release of molecules wrapped in the outer shell, and controlled diffusion of antimicrobials stored in the inner shell by electrostatic interaction, resulting in a long-lasting mildew resistance for up to 71 days. The versatility of the hierarchical interactions of HoMSs will inspire the design of promising smart drug carriers.

Synthesis of stimulus-responsive ABC triblock fluorinated polyether amphiphilic polymer and application as low toxicity smart drug carrier

Polymeric surfactants based on hydrocarbon polyether structure, have been used in many pharmaceutical formulations and drug delivery for many years. However, nowadays, developing novel drugs is often accompanied by introducing fluoride atom, inhibiting the application scope of traditional hydrocarbon surfactants. Thus, we argued it is necessary to develop novel fluorinated polyether polymeric surfactant. Herein, poly(ethylene glycol) monomethyl ether was used to initiate the living cationic polymerization of fluorinated epichlorohydrin (EPTF) prepared by our group and (R)-glycidyl butyrate to obtain a type of triblock fluorinated polyether amphiphilic polymer, which possesses stimulus-responsive characteristic in the presence of acid and enzyme. The structure of this triblock fluorinated polyether amphiphilic polymer was confirmed by spectroscopic data. And the critical micelles concentration of this surfactant was relatively low representing their excellent surface activity. CCK-8 test showed that this triblock fluorinated polyether amphiphilic polymer displayed no toxic effect on NIH3T3 cells even its concentration reached to 1 g/L. Therefore, we design and obtain a kind of triblock fluorinated polyether amphiphilic polymer possessing low toxicity and stimulus-responsive characteristic which can also be used to improve the solubility of baicalin.

Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system.

Since the beginning of pharmaceutical research, drug delivery methods have been an integral part of it. Polymeric micelles (PMs) have emerged as multifunctional nanoparticles in the current technological era of nanocarriers, and they have shown promise in a range of scientific fields. They can alter the release profile of integrated pharmacological substances and concentrate them in the target zone due to their improved permeability and retention, making them more suitable for poorly soluble medicines. With their ability to deliver poorly soluble chemotherapeutic drugs, PMs have garnered considerable interest in cancer. As a result of their remarkable biocompatibility, improved permeability, and minimal toxicity to healthy cells, while also their capacity to solubilize a wide range of drugs in their micellar core, PMs are expected to be a successful treatment option for cancer therapy in the future. Their nano-size enables them to accumulate in the tumor microenvironment (TME) via the enhanced permeability and retention (EPR) effect. In this review, our major aim is to focus primarily on the stellar applications of PMs in the field of cancer therapeutics along with its mechanism of action and its latest advancements in drug and gene delivery (DNA/siRNA) for cancer, using various therapeutic strategies such as crossing blood-brain barrier, gene therapy, photothermal therapy (PTT), and immunotherapy. Furthermore, PMs can be employed as "smart drug carriers," allowing them to target specific cancer sites using a variety of stimuli (endogenous and exogenous), which improve the specificity and efficacy of micelle-based targeted drug delivery. All the many types of stimulants, as well as how the complex of PM and various anticancer drugs react to it, and their pharmacodynamics are also reviewed here. In conclusion, commercializing engineered micelle nanoparticles (MNPs) for application in therapy and imaging can be considered as a potential approach to improve the therapeutic index of anticancer drugs. Furthermore, PM has stimulated intense interest in research and clinical practice, and in light of this, we have also highlighted a few PMs that have previously been approved for therapeutic use, while the majority are still being studied in clinical trials for various cancer therapies.