Polymeric Nanocarriers Research Articles

Unveiling the potential of photodynamic therapy with nanocarriers as a compelling therapeutic approach for skin cancer treatment: current explorations and insights.

Skin carcinoma is one of the most prevalent types of carcinomas. Due to high incidence of side effects in conventional therapies (radiotherapy and chemotherapy), photodynamic therapy (PDT) has gained huge attention as an alternate treatment strategy. PDT involves the administration of photosensitizers (PS) to carcinoma cells which produce reactive oxygen species (ROS) on irradiation by specific wavelengths of light that result in cancer cells' death via apoptosis, autophagy, or necrosis. Topical delivery of PS to the skin cancer cells at the required concentration is a challenge due to the compounds' innate physicochemical characteristics. Nanocarriers have been observed to improve skin permeability and enhance the therapeutic efficiency of PDT. Polymeric nanoparticles (NPs), metallic NPs, and lipid nanocarriers have been reported to carry PS successfully with minimal side effects and high effectiveness in both melanoma and non-melanoma skin cancers. Advanced carriers such as quantum dots, microneedles, and cubosomes have also been addressed with reported studies to show their scope of use in PDT-assisted skin cancer treatment. In this review, nanocarrier-aided PDT in skin cancer therapies has been discussed with clinical trials and patents. Additionally, novel nanocarriers that are being investigated in PDT are also covered with their future prospects in skin carcinoma treatment.

Nanocarrier-based gene delivery for immune cell engineering.

Clinical advances in genetically modified immune cell therapies, such as chimeric antigen receptor T cell therapies, have raised hope for cancer treatment. The majority of these biotechnologies are based on viral methods for ex vivo genetic modification of the immune cells, while the non-viral methods are still in the developmental phase. Nanocarriers have been emerging as materials of choice for gene delivery to immune cells. This is due to their versatile physicochemical properties such as large surface area and size that can be optimized to overcome several practical barriers to successful gene delivery. The in vivo nanocarrier-based gene delivery can revolutionize cell-based cancer immunotherapies by replacing the current expensive autologous cell manufacturing with an off-the-shelf biomaterial-based platform. The aim of this research is to review current advances and strategies to overcome the challenges in nanoparticle-based gene delivery and their impact on the efficiency, safety, and specificity of the process. The main focus is on polymeric and lipid-based nanocarriers, and their recent preclinical applications for cancer immunotherapy.

Stimuli-responsive polymer-based nanosystems for cardiovascular disease theranostics.

Stimulus-responsive polymers have found widespread use in biomedicine due to their ability to alter their own structure in response to various stimuli, including internal factors such as pH, reactive oxygen species (ROS), and enzymes, as well as external factors like light. In the context of atherosclerotic cardiovascular diseases (CVDs), stimulus-response polymers have been extensively employed for the preparation of smart nanocarriers that can deliver therapeutic and diagnostic drugs specifically to inflammatory lesions. Compared with traditional drug delivery systems, stimulus-responsive nanosystems offer higher sensitivity, greater versatility, wider applicability, and enhanced biosafety. Recent research has made significant contributions towards designing stimulus-responsive polymer nanosystems for CVDs diagnosis and treatment. This review summarizes recent advances in this field by classifying stimulus-responsive polymer nanocarriers according to different responsiveness types and describing numerous stimuli relevant to these materials. Additionally, we discuss various applications of stimulus-responsive polymer nanomaterials in CVDs theranostics. We hope that this review will provide valuable insights into optimizing the design of stimulus-response polymers for accelerating their clinical application in diagnosing and treating CVDs.

Citrus Flavonones into nanotechnology-based formulations to skin treatment

Introduction: Flavonones show potential application in the treatment of skin disorders, whose performance may be improved by using lipid and polymeric nanocarriers. In this review, a recent approach regarding nanocarriers containing either naringin, naringenin, hesperidin or hesperitin for skin application are discussed. Method: This review approaches the publications from the last 6 years about nanosystems containing Citrus flavonones for cutaneous applications. The articles were selected by searching in Scopus database for nanosystem containing either hesperidin, hesperitin, naringin or naringenin for cutaneous application, research articles written in English and published between 2018 and 2023, and reporting about skin penetration or biological evaluation. Results: Majority of reports employed lipid systems as nanocarriers. Naringenin was the most used flavonone. In relation to skin benefits, improved wound healing, atopic dermatitis treatment and stress oxidative-related diseases are highlighted. Despite the probable benefits, the development of plant-based nanomedicines is complex, which imposes limitations on the development of new pharmaceutical products. Further, the potential of flavonoids in the treatment of skin cancer has been shown. Conclusions: Lipid, polymeric and nanohybrid carriers are employed to deliver flavanones. Due to their antioxidant and anti-inflammatory activities, flavanones bear potential applications in the treatment of different skin disorders. Therefore, there is a promising application of flavanones to the improvement of human health, mainly with their loading into nanocarriers.

Polymeric nanoparticles delivery circumvents bacterial resistance to ciprofloxacin

Polymeric nanoparticles delivery circumvents bacterial resistance to ciprofloxacin

Fabrication of GSH‐Responsive Poly(Tertiary Amine‐Oxide)‐Based Nanomedicines for Enhanced Anticancer Drug Release

AbstractPoly(tertiary amine‐oxide)‐based polymeric nanocarriers have showed more functionalities than stealthy PEG‐based analogs due to the structure of phospholipid affinitive N‐oxides groups, which has attracted considerable attention to the synthesis of various zwitterionic copolymers with tertiary amine‐oxide grafts for enhanced anticancer drug delivery. However, poly(tertiary amine‐oxide)‐based amphiphilic copolymers with tumor intracellular microenvironment sensitivities, to the knowledge, have been rarely reported likely due to the lack of a controlled synthetic strategy. Herein, a reducible zwitterionic copolymer, poly(ε‐caprolactone)25‐SS‐poly(2‐(N‐oxide‐N,N‐diethylamino)ethyl methacrylate)30 (PCL25‐SS‐OPDEA30) is designed and synthesized successfully via combination of controlled polymerization techniques and post polymerization modification. Specifically, postoxidation of poly(tertiary amine) is confirmed to be a better synthetic strategy toward a well‐defined polymer structure relative to direct polymerization of N,N‐diethylaminoethyl methacrylate (ODEA). The effect of disulfide bridges on the self‐assembly behaviors, in vitro drug loading and drug release properties is investigated in detail. Notablely, the resulting micelles self‐assembled from PCL25‐SS‐OPDEA30 show much greater colloidal stability, higher drug loading content (DLC), and better in vitro tumor cell inhibition than the reduction‐insensitive counterparts. Overall, this study reports a robust strategy toward zwitterionic nanomedicines for on‐demand anticancer drug delivery.

Reaching the Tumor: Mobility of Polymeric Micelles Inside an In Vitro Tumor-on-a-Chip Model with Dual ECM.

Degradable polymeric micelles are promising drug delivery systems due to their hydrophobic core and responsive design. When applying micellar nanocarriers for tumor delivery, one of the bottlenecks encountered in vivo is the tumor tissue barrier: crossing the dense mesh of cells and the extracellular matrix (ECM). Sometimes overlooked, the extracellular matrix can trap nanoformulations based on charge, size, and hydrophobicity. Here, we used a simple design of a microfluidic chip with two types of ECM and MCF7 spheroids to allow "high-throughput" screening of the interactions between biological interfaces and polymeric micelles. To demonstrate the applicability of the chip, a small library of fluorescently labeled polymeric micelles varying in their hydrophilic shell and hydrophobic core forming blocks was studied. Three widely used hydrophilic shells were tested and compared, namely, poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid), along with two enzymatically degradable dendritic hydrophobic cores (based on hexyl or nonyl end groups). Using ratiometric imaging of unimer:micelle fluorescence and FRAP inside the chip model, we obtained the local assembly state and dynamics inside the chip. Notably, we observed different micelle behaviors in the basal lamina ECM, from avoidance of the ECM structure to binding of the poly(acrylic acid) formulations. Binding to the basal lamina correlated with higher uptake into MCF7 spheroids. Overall, we proposed a simple microfluidic chip containing dual ECM and spheroids for the assessment of the interactions of polymeric nanocarriers with biological interfaces and evaluating nanoformulations' capacity to cross the tumor tissue barrier.

Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics.

Stimuli-responsive polymers can respond to internal stimuli, such as reactive oxygen species (ROS), glutathione (GSH), and pH, biological stimuli, such as enzymes, and external stimuli, such as lasers and ultrasound, etc., by changing their hydrophobicity/hydrophilicity, degradability, ionizability, etc., and thus have been widely used in biomedical applications. Due to the characteristics of the tumor microenvironment (TME), stimuli-responsive polymers that cater specifically to the TME have been extensively used to prepare smart nanovehicles for the targeted delivery of therapeutic and diagnostic agents to tumor tissues. Compared to conventional drug delivery nanosystems, TME-responsive nanosystems have many advantages, such as high sensitivity, broad applicability among different tumors, functional versatility, and improved biosafety. In recent years, a great deal of research has been devoted to engineering efficient stimuli-responsive polymeric nanosystems, and significant improvement has been made to both cancer diagnosis and therapy. In this review, we summarize some recent research advances involving the use of stimuli-responsive polymer nanocarriers in drug delivery, tumor imaging, therapy, and theranostics. Various chemical stimuli will be described in the context of stimuli-responsive nanosystems. Accordingly, the functional chemical groups responsible for the responsiveness and the strategies to incorporate these groups into the polymer will be discussed in detail. With the research on this topic expending at a fast pace, some innovative concepts, such as sequential and cascade drug release, NIR-II imaging, and multifunctional formulations, have emerged as popular strategies for enhanced performance, which will also be included here with up-to-date illustrations. We hope that this review will offer valuable insights for the selection and optimization of stimuli-responsive polymers to help accelerate their future applications in cancer diagnosis and treatment.

Development of a Polymeric Pharmacological Nanocarrier System as a Potential Therapy for Spinocerebellar Ataxia Type 7.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant inherited disease characterized by progressive ataxia and retinal degeneration. SCA7 belongs to a group of neurodegenerative diseases caused by an expanded CAG repeat in the disease-causing gene, resulting in aberrant polyglutamine (polyQ) protein synthesis. PolyQ ataxin-7 is prone to aggregate in intracellular inclusions, perturbing cellular processes leading to neuronal death in specific regions of the central nervous system (CNS). Currently, there is no treatment for SCA7; however, a promising approach successfully applied to other polyQ diseases involves the clearance of polyQ protein aggregates through pharmacological activation of autophagy. Nonetheless, the blood-brain barrier (BBB) poses a challenge for delivering drugs to the CNS, limiting treatment effectiveness. This study aimed to develop a polymeric nanocarrier system to deliver therapeutic agents across the BBB into the CNS. We prepared poly(lactic-co-glycolic acid) nanoparticles (NPs) modified with Poloxamer188 and loaded with rapamycin to enable NPs to activate autophagy. We demonstrated that these rapamycin-loaded NPs were successfully taken up by neuronal and glial cells, demonstrating high biocompatibility without adverse effects. Remarkably, rapamycin-loaded NPs effectively cleared mutant ataxin-7 aggregates in a SCA7 glial cell model, highlighting their potential as a therapeutic approach to fight SCA7 and other polyQ diseases.

CCL2 chemokine inhibition primes the tumor vasculature for improved nanomedicine delivery and efficacy

Blood vessel functionality is crucial for efficient tumor-targeted drug delivery. Heterogeneous distribution and perfusion of angiogenic blood vessels contribute to suboptimal accumulation of (nano-) therapeutics in tumors and metastases. To attenuate pathological angiogenesis, an L-RNA aptamer inhibiting the CC motif chemokine ligand 2 (CCL2) was administered to mice bearing orthotopic 4T1 triple-negative breast cancer tumors. The effect of CCL2 inhibition on tumor blood vessel functionality and tumor-targeted drug delivery was evaluated via multimodal and multiscale optical imaging, employing fluorophore-labeled polymeric (10 nm) and liposomal (100 nm) nanocarriers. Anti-CCL2 treatment induced a dose-dependent anti-angiogenic effect, reflected by a decreased relative blood volume, increased blood vessel maturity and functionality, and reduced macrophage infiltration, accompanied by a shift in the polarization of tumor-associated macrophages (TAM) towards a less M2-like and more M1-like phenotype. In line with this, CCL2 inhibitor treatment improved the delivery of polymers and liposomes to tumors, and enhanced the antitumor efficacy of free and liposomal doxorubicin. Together, these findings demonstrate that blocking the CCL2-CCR2 axis modulates TAM infiltration and polarization, resulting in vascular normalization and improved tumor-targeted drug delivery.

QbD-driven RP-HPLC method for novel chemo-herbal combination, in-silico, force degradation studies, and characterization of dual drug-loaded polymeric and lipidic nanocarriers

BackgroundIn cancer therapies, chemo-herbal combinations are receiving increased attention. A multiple tyrosine kinase inhibitor, lenvatinib (LTB) is beneficial in treating thyroid, lung, endometrial, and liver cancers. An isoflavone called biochanin A (BCA) is well known for its diverse biological properties that have been studied to potentiate the anti-cancer potential and lower the normal cell toxicities of other therapeutics. LTB and BCA can be combined for cancer treatment and may increase their therapeutic potential at lower doses. In brief, the quality by design (QbD)-driven RP-HPLC method was developed, validated, and utilized for applications employing the study of forced degradants and the successful development of LTB and BCA co-loaded nanocarriers.ResultsThe RP-HPLC method employed Box–Behnken design with peak resolution 6.70 ± 0.006, tailing factor 1.06 ± 0.05 for BCA and 1.17 ± 0.021 for LTB, and theoretical plates number > 2000. RP-HPLC applications utilized the investigation of a total of 41.17% and 70.58% degradants for LTB and BCA in contrast to in-silico predicted studies using Zeneth software. The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) were formed with particle size 185.3 ± 12.3 nm, zeta potential − 13.3 ± 0.35 mV, and percentage entrapment efficiency (%EE) for the LTB and BCA 53.64 ± 4.81% and 61.29 ± 4.67%, respectively. However, the developed Cubosomes (CBs) exhibited 182.4 ± 16.3 nm aerodynamic particle size, − 10.8 ± 0.39 mV zeta potential, and % EE for LTB and BCA 55.62 ± 7.73% and 72.88 ± 5.52%, respectively. The percentage drug loading (%DL) of LTB and BCA from PLGA NPs was found to be 3.7 ± 0.46% and 4.63 ± 0.48%, whereas CBs exhibited higher % DL for BCA (5.42 ± 1.10%) and LTB (4.43 ± 0.77%).ConclusionThe RP-HPLC method was developed and validated according to ICH and USP guidelines. In-vitro and in-silico forced degradation studies are evident to quantify the type of degradant and its exact mechanism of degradation. In-silico toxicity assessment for LTB, BCA, and their degradants explains the necessity of conducting degradation studies during drug development. Finally, the applications of the developed RP-HPLC method explain the usefulness of analytical methods in the development of chemo-herbal drug nanocarriers (polymeric and lipidic).Graphical abstract

Efficient and Targeted siRNA Delivery to M2 Macrophages by Smart Polymer Blends for M1 Macrophage Repolarization as a Promising Strategy for Future Cancer Treatment.

Cancer remains an issue on a global scale. It is estimated that nearly 10 million people succumbed to cancer worldwide in 2020. New treatment options are urgently needed. A promising approach is a conversion of tumor-promoting M2 tumor-associated macrophages (TAMs) as part of the tumor microenvironment to tumor-suppressive M1 TAMs by small interfering RNA (siRNA). In this work, we present a well-characterized polymeric nanocarrier system capable of targeting M2 TAMs by a ligand-receptor interaction. Therefore, we developed a blended PEI-based polymeric nanoparticle system conjugated with mannose, which is internalized after interaction with macrophage mannose receptors (MMRs), showing low cytotoxicity and negligible IL-6 activation. The PEI-PCL-PEI (5 kDa-5 kDa-5 kDa) and Man-PEG-PCL (2 kDa-2 kDa) blended siRNA delivery system was optimized for maximum targeting capability and efficient endosomal escape by evaluation of different polymer and N/P ratios. The nanoparticles were formulated by surface acoustic wave-assisted microfluidics, achieving a size of ∼80 nm and a zeta potential of approximately +10 mV. Special attention was given to the endosomal escape as the so-called bottleneck of RNA drug delivery. To estimate the endosomal escape capability of the nanocarrier system, we developed a prediction method by evaluating the particle stability via the inflection temperature. Our predictions were then verified in an in vitro setting by applying confocal microscopy. For cellular experiments, however, human THP-1 cells were polarized to M2 macrophages by cytokine treatment and validated through MMR expression. To show the efficiency of the nanoparticle system, GAPDH and IκBα knockdown was performed in the presence or absence of an MMR blocking excess of mannan. Cellular uptake, GAPDH knockdown, and NF-κB western blot confirmed efficient mannose targeting. Herein, we presented a well-characterized nanoparticle delivery system and a promising approach for targeting M2 macrophages by a mannose-MMR interaction.

Antibacterial photodynamic inactivation with elicited Andrographis paniculata (Burm. f.) Wall. ex Nees plant extract derived carbonaceous nanoparticle

BackgroundConversion of phytoproducts into nanoparticles for antimicrobial intervention is common but employing elicitation to the plant to achieve dual and more potent chemical and photodynamic effects is seldom researched or achieved. PurposeAntimicrobial photodynamic inactivation using nanotized plant extracts of Andrographis paniculata in the form of a carbonaceous nanoparticle is established here through the fabrication of a Carbon Dot (CD). Study designLeaves extracts of Plant growth promoting bacteria (PGPR) elicited plants are transformed to CD to induce unique photophysical properties without any surface modification and passivation to achieve the enhanced antimicrobial activity. MethodsCD with diameter ∼ 20 nm synthesized through hydrothermal pyrolysis of elicited A. paniculata leaf extracts. The nanoscale dimensions and photophysical characteristics of the CD were confirmed by Transmission electron microscopy (TEM), powder X-ray diffraction (XRD), Ultraviolet-visible (UV–Vis), Fluorescence, and Fourier transform infrared spectroscopy (FTIR) characterizations. Antibacterial activity in both Gram-positive and Gram-negative bacteria was evaluated to determine the combined effect of the dark activity and visible light-induced photosensitization. ResultsSecondary metabolites are elicited by microbial inoculation to form nanotized phytoproducts in the present study, which does not rely on any polymeric or lipidic nanocarriers. In vitro, studies showed that the antibacterial effects of CDs against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) under the irradiation of visible light depend on the bioactive components, their concentrations, and duration of light irradiation. The CD itself sustainably acts as a photo-antibiotic as well as produces reactive oxygen species (ROS). ConclusionThis study showed that PGPR elicited leaf extracts of A. paniculata-derived CDs used as antibiotic therapy, due to its effectiveness in eliminating synthetic drug-resistant microbes through reactive oxygen species (ROS) via photodynamic inactivation. In comparison to the unelicited phyto substrate, it served as a more effective option for “Natural-Antibiotic-Antibacterial Photodynamic Therapy” (APDT) applications.

Aerosol assisted synthesis of a pH responsive curcumin anticancer drug nanocarrier using chitosan and alginate natural polymers

In recent years, several nanocarrier synthesis methods have been developed. In cancer therapy, the use of smart nanocarriers is of interest. Smart nanocarriers respond to their environment and can release their cargo in a controlled manner under the action of internal or external stimuli. In this work, we report on the development of an aerosol-assisted method for the synthesis of curcumin-loaded chitosan/alginate-based polymeric nanocarrier (CurNCs). A custom-fabricated multi-nebulizer system was utilized for the synthesis of CurNCs. The developed system comprises three main parts a sprayer, an electric heater tunnel, and a collector. Curcumin and chitosan solutions were sprayed using a pneumatic multinebulizer into the electric heater tunnel to form chitosan-curcumin assemblies. Then, the aerosol was guided into the collector solution containing sodium alginate and tri-poly phosphate aqueous solution for further cross-linkage. The synthesized CurNCs were characterized using TEM, DLS, and FTIR techniques. The TEM size of the nanoparticles was 8.62 ± 2.25 nm. The release experiments revealed that the nanocarrier is sensitive to the environment pH as more curcumin is released at acidic pH values (as is the case for cancerous tissues) compared to physiological pH. The curcumin content of the nanocarrier was 77.27 mg g−1 with a drug loading efficiency of 62%. The in-vitro cytotoxicity of the synthesized nanocarrier was evaluated against the MCF7 breast cancer cell line. The IC50 concentrations for CurNCs and curcumin were obtained as 14.86 and 16.45 mg mL−1, respectively. The results showed that while the empty nanocarrier shows non-significant cytotoxicity, the CurNCs impact the cell culture and cause prolonged cell deaths. Overall, pH-responsive curcumin polymeric nanocarrier was synthesized using a custom fabricated aerosol-based method. The method enabled fast and feasible synthesis of the nanocarrier with high efficiency.

Nanocarrier of α-Tocopheryl Succinate Based on a Copolymer Derivative of (4,7-dichloroquinolin-2-yl)methanol and Its Cytotoxicity against a Breast Cancer Cell Line.

In order to improve the water solubility and, therefore, bioavailability and therapeutic activity of anticancer hydrophobic drug α-tocopherol succinate (α-TOS), in this work, copolymers were synthesized via free radicals from QMES (1-[4,7-dichloroquinolin-2-ylmethyl]-4-methacryloyloxyethyl succinate) and VP (N-vinyl-2-pirrolidone) using different molar ratios, and were used to nanoencapsulate and deliver α-TOS into cancer cells MCF-7. QMES monomer was chosen because the QMES pendant group in the polymer tends to hydrolyze to form free 4,7-dichloro-2-quinolinemethanol (QOH), which also, like α-TOS, exhibit anti-proliferative effects on cancerous cells. From the QMES-VP 30:70 (QMES-30) and 40:60 (QMES-40) copolymers obtained, it was possible to prepare aqueous suspensions of empty nanoparticles (NPs) loaded with α-TOS by nanoprecipitation. The diameter and encapsulation efficiency (%EE) of the QMES-30 NPs loaded with α-TOS were 128.6 nm and 52%; while for the QMES-40 NPs loaded with α-TOS, they were 148.8 nm and 65%. The results of the AlamarBlue assay at 72 h of treatment show that empty QMES-30 NPs (without α-TOS) produced a marked cytotoxic effect on MCF-7 breast cancer cells, corresponding to an IC50 value of 0.043 mg mL-1, and importantly, they did not exhibit cytotoxicity against healthy HUVEC cells. Furthermore, NP-QMES-40 loaded with α-TOS were cytotoxic with an IC50 value of 0.076 mg mL-1, demonstrating a progressive release of α-TOS; however, the latter nanoparticles were also cytotoxic to healthy cells in the range of the assayed concentrations. These results contribute to the search for a new polymeric nanocarrier of QOH, α-TOS or other hydrophobic drugs for the treatment of cancer or others diseases treatable with these drugs.

Therapeutic activity and biodistribution of a nano-sized polymer-dexamethasone conjugate intended for the targeted treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory autoimmune disease caused by alteration of the immune system. Current therapies have several limitations and the use of nanomedicines represents a promising strategy to overcome them. By employing a mouse model of adjuvant induced arthritis, we aimed to evaluate the biodistribution and therapeutic effects of glucocorticoid dexamethasone conjugated to a nanocarrier based on biocompatible N-(2-hydroxypropyl) methacrylamide copolymers. We observed an increased accumulation of dexamethasone polymer nanomedicines in the arthritic mouse paw using non-invasive fluorescent in vivo imaging and confirmed it by the analysis of tissue homogenates. The dexamethasone conjugate exhibited a dose-dependent healing effect on arthritis and an improved therapeutic outcome compared to free dexamethasone. Particularly, significant reduction of accumulation of RA mediator RANKL was observed. Overall, our data suggest that the conjugation of dexamethasone to a polymer nanocarrier by means of stimuli-sensitive spacer is suitable strategy for improving rheumatoid arthritis therapy.

Inorganic Nanoparticles Embedded in Polydimethylsiloxane Nanodroplets.

To stabilize and transport them through complex systems, nanoparticles are often encapsulated in polymeric nanocarriers, which are tailored to specific environments. For example, a hydrophilic polymer capsule maintains the circulation and stability of nanoparticles in aqueous environments. A more highly designed nanocarrier might have a hydrophobic core and a hydrophilic shell to allow the transport of hydrophobic nanoparticles and pharmaceuticals through physiological media. Polydimethylsiloxane, PDMS, is a hydrophobic material in a liquid-like state at room temperature. The preparation of stable, aqueous dispersions of PDMS droplets in water is problematic due to the intense mismatch in surface energies between PDMS and water. The present work describes the encapsulation of hydrophobic metal and metal oxide nanoparticles within PDMS nanodroplets using flash nanoprecipitation. The PDMS is terminated by amino groups, and the nanodroplet is capped with a layer of poly(styrenesulfonate), forming a glassy outer shell. The hydrophobic nanoparticles nucleate PDMS droplet formation, decreasing the droplet size. The resulting nanocomposite nanodroplets are stable in aqueous salt solutions without the use of surfactants. The hierarchical structuring, elucidated with small-angle X-ray scattering, offers a new platform for the isolation and transport of hydrophobic molecules and nanoparticles through aqueous systems.

In silico engineering and simulation of RNA interferences nanoplatforms for osteoporosis treating and bone healing promoting

Osteoporosis is a bone condition characterized by reduced bone mineral density (BMD), poor bone microarchitecture/mineralization, and/or diminished bone strength. This asymptomatic disorder typically goes untreated until it presents as a low-trauma fracture of the hip, spine, proximal humerus, pelvis, and/or wrist, requiring surgery. Utilizing RNA interference (RNAi) may be accomplished in a number of ways, one of which is by the use of very tiny RNA molecules called microRNAs (miRNAs) and small interfering RNAs (siRNAs). Several kinds of antagomirs and siRNAs are now being developed to prevent the detrimental effects of miRNAs. The goal of this study is to find new antagonists for miRNAs and siRNAs that target multiple genes in order to reduce osteoporosis and promote bone repair. Also, choosing the optimum nanocarriers to deliver these RNAis appropriately to the body could lighten up the research road. In this context, we employed gene ontology analysis to search across multiple datasets. Following data analysis, a systems biology approach was used to process it. A molecular dynamics (MD) simulation was used to explore the possibility of incorporating the suggested siRNAs and miRNA antagonists into polymeric bioresponsive nanocarriers for delivery purposes. Among the three nanocarriers tested [polyethylene glycol (PEG), polyethylenimine (PEI), and PEG-PEI copolymer], MD simulations show that the integration of PEG-PEI with has-mIR-146a-5p is the most stable (total energy = -372.84 kJ/mol, Gyration radius = 2.1084 nm), whereas PEI is an appropriate delivery carrier for has-mIR-7155. The findings of the systems biology and MD simulations indicate that the proposed RNAis might be given through bioresponsive nanocarriers to accelerate bone repair and osteoporosis treatment.

New Advances in Nano-Enabled Weed Management Using Poly(Epsilon-Caprolactone)-Based Nanoherbicides: A Review

The number of effective herbicides available to farmers is steadily decreasing due to increasing herbicide resistance. It seems very important to address and effectively deal with the main weed management challenges (low crop yield and environmental pollution) by investigating the potential of newly introduced materials, such as biocompatible polymer-based nanoparticles. The current review aims to encourage agricultural or environmental researchers to conduct new research on the synthesis and application of modified herbicides, such as nanoherbicides, for application in weed management and to provide a comprehensive foundation on the topic. Such nanosystems could help with the promotion of the controlled release of active ingredients and extend their action time, resulting in a reduction in dose and application number; improve the physical and chemical characteristics of the herbicide to increase foliar adhesion; prevent degradation that results from environmental factors (such as sunlight, temperature, microorganisms, or pH); and decrease herbicide leaching and contamination of the environment. Furthermore, it has been indicated that some polymeric nanocarriers can penetrate biological barriers, including membranes and plant cell walls, and translocate across vascular tissues, resulting in a more efficient delivery of active ingredients. Poly(epsilon-caprolactone) is a biocompatible material that is easily decomposable by enzymes and fungi. PCL nanoparticles could be applied as nanocarriers of herbicides in agriculture due to their low toxicity, their potential for large-scale synthesis from inexpensive materials, their ability to dissolve herbicides, their high loading capacity, and their ability to help minimize the chemical decomposition of herbicides.

Design of bio-scaffold conjugated with chitosan-PEG nano-carriers containing bio-macromolecules of Verbascum sinuatum L. to differentiate human adipose-derived stem cells into dermal keratinocytes

Regenerative medicine and drug delivery systems provide promising approaches for the treatment of skin lesions. However, the design of engineered substrates containing therapeutic agents for cell proliferation and its differentiation into skin cells, with skin-like patterns, is the major challenge. Here, to overcome this problem, a hybrid scaffold conjugated with nanoparticles containing the extract of Verbascum sinuatum L. flowers (HE) was designed. To this end, (chitosan-PEG)-based nanocarriers (Chi-PEG) were first prepared in the volume ratios of 90:10, 80:20, 70:30, and 50:50 v/v. The results indicated that the 70:30 ratio possessed better physical/morphologic properties along with more suitable stability than other nanoparticles (encapsulation-efficiency:86.34 %, zeta-potential:21.2 mV, and PDI:0.30). Afterward, PCL-collagen biologic scaffold (PCL-Coll) were prepared by the lyophilization method, then conjugated with selected nanoparticles(Chi-PEG70:30-HE). Notably, in addition to PCL-Coll/Chi-PEG-HE, two scaffolds of PCL-Coll and PCL-Coll/Chi-PEG were prepared to evaluate the role of conjugation in the release behavior of herbal bio-macromolecules. Based on the results, the conjugation process was led to a more stable release, compared to unconjugated nanoparticles. The mentioned process also created an integrated network along with better physicomechanical properties [modulus:12.31 MPa, tensile strength:4.44 MPa, smaller pore size(2 μm), and better swelling (100.27 %) with a symmetrical wettability on the surface]. PCL-Coll/Chi-PEG-HE scaffold was also resulted in higher expression levels of K10 and K14 keratinocytes with biomimetic patterns than PCL-Coll/Chi-PEG scaffold. This could be due to the active ingredients of V. sinuatum extract like alkaloids, flavonoids, and triterpenoids which imparts the wound healing (anti-inflammatory, anti-bacterial, anti-oxidant) properties to this scaffold. It seems that the use of bioactive materials like herbal extracts, in the form of encapsulated into polymeric nanocarriers, in the structure of engineered scaffolds can be a promising option for regenerating damaged skin without scarring. Hence, this study can provide innovative insights into the combination of two techniques of drug delivery and tissue engineering to design bio-scaffolds containing bioactive molecules with better therapeutic approaches.