Ideal Delivery System Research Articles

Optimal delivery strategies for nanoparticle-mediated mRNA delivery.

Messenger RNA (mRNA) has emerged as a new and efficient agent for the treatment of various diseases. The success of lipid nanoparticle-mRNA against the novel coronavirus (SARS-CoV-2) pneumonia epidemic has proved the clinical potential of nanoparticle-mRNA formulations. However, the deficiency in the effective biological distribution, high transfection efficiency and good biosafety are still the major challenges in clinical translation of nanomedicine for mRNA delivery. To date, a variety of promising nanoparticles have been constructed and then gradually optimized to facilitate the effective biodistribution of carriers and efficient mRNA delivery. In this review, we describe the design of nanoparticles with an emphasis on lipid nanoparticles, and discuss the manipulation strategies for nanoparticle-biology (nano-bio) interactions for mRNA delivery to overcome the biological barriers and improve the delivery efficiency, because the specific nano-bio interaction of nanoparticles usually remoulds the biomedical and physiological properties of the nanoparticles especially the biodistribution, mechanism of cellular internalization and immune response. Finally, we give a perspective for the future applications of this promising technology. We believe that the regulation of nano-bio interactions would be a significant breakthrough to improve the mRNA delivery efficiency and cross biological barriers. This review may provide a new direction for the design of nanoparticle-mediated mRNA delivery systems.

An Updated Review on Preparation and Characterization of Solid Lipid Nanoparticles

Drug delivery technology has a wide spectrum, which is continuously being upgraded at a stupendous speed. Different fabricated nanoparticles and drugs possessing low solubility and poor pharmacokinetic profiles are the two major substances extensively delivered to target sites. Among the colloidal carriers, nanolipid dispersions (liposomes, deformable liposomes, virosomes, ethosomes, and solid lipid nanoparticles) are ideal delivery systems with the advantages of biodegradation and nontoxicity. Among them, nano-structured lipid carriers and solid lipid nanoparticles (SLNs) are dominant, which can be modified to exhibit various advantages, compared to liposomes and polymeric nanoparticles. Nano-structured lipid carriers and SLNs are non-biotoxic since they are biodegradable. Besides, they are highly stable. Their (nano-structured lipid carriers and SLNs) morphology, structural characteristics, ingredients used for preparation, techniques for their production, and characterization using various methods are discussed in this review. Also, although nano-structured lipid carriers and SLNs are based on lipids and surfactants, the effect of these two matrixes to build excipients is also discussed together with their pharmacological significance with novel theranostic approaches, stability and storage. Solid lipid nanoparticles (SLN) are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Due to their unique size dependent properties, lipid nanoparticles offer possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could use for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their aims, production procedures, advantages, limitations and their possible remedies. Appropriate analytical techniques for the characterization of SLN like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of SLN route of administration and the in vivo fate of the carriers are also discussed.

The complexing of cationic copolymer MPC30-DEA70 with TGF-β1 antisense oligodeoxynucleotide and transfection into cardiomyocytes in vitro.

Although gene therapy is an attractive option for the treatment of cardiovascular diseases, the ideal gene delivery systems are still under investigation and must meet the following criteria: safety, adequate gene transfer efficiency, and stable expression of the transgene for a duration appropriate for treating the disease. In this study, we developed a cationic phosphorylcholine-containing diblock copolymer, namely MPC30-DEA70, as carrier systems to deliver a chemically synthesized transforming growth factor-beta 1(TGF-β1) antisense oligonucleotide (AS-ODN) into cardiomyocytes (CMs) to observe the cell transfection efficiency of MPC30-DEA70 and the inhibition effect on the expression of TGF-β1. MPC30-DEA70/TGF-β1 AS-ODN complexes were formed through complexation between copolymer MPC30-DEA70 (N) and AS-ODN (P) at different N/P ratios and were characterized by DNA electrophoresis. Notably, the cytotoxicity and cell growth inhibition assay showed that the MPC30-DEA70 had low cytotoxicity to CMs within the effective transfection dosage range (<20μL/mL). CLSM/TEM images displayed that most of the AS-ODN molecules engulfed by cells were located around the cell nuclei, and a few entered into the cell nuclei without harming the organelles in the cell. Transfection studies from CMs indicated a steady increase of transfection efficiency with increasing N/P ratios. The expression levels of TGF-β1 mRNA and protein in CMs were significantly inhibited at high N/P ratios. This study shows that MPC30-DEA70 can function as an effective transgenic vector into CMs and that TGF-β1 AS-ODN delivered by MPC30-DEA70 can silence the expression of the TGF-β1 gene efficiently and specifically and thereafter antagonize TGF-β1-mediated biological function in cardiomyocytes.

Bridging nanoplatform and vaccine delivery, a landscape of strategy to enhance nasal immunity.

Vaccination is an urgently needed and effective option to address epidemic, cancers, allergies, and other diseases. Nasal administration of vaccines offers many benefits over needle-based injection including high compliance and less risk of infection. Inactivated or attenuated vaccines as convention vaccine present potential risks of pathogenic virulence reversal, the focus of nasal vaccine development has shifted to the use of next-generation (subunit and nucleic acid) vaccines. However, subunit and nucleic acid vaccine intranasally have numerous challenges in development and utilization due to mucociliary clearance, mucosal epithelial tight junction, and enzyme/pH degradation. Nanoplatforms as ideal delivery systems, with the ability to enhance the retention, penetration, and uptake of nasal mucosa, shows great potential in improving immunogenic efficacy of nasal vaccine. This review provides an overview of delivery strategies for overcoming nasal barrier, including mucosal adhesion, mucus penetration, targeting of antigen presenting cells (APCs), enhancement of paracellular transportation. We discuss methods of enhancing antigen immunogenicity by nanoplatforms as immune-modulators or multi-antigen co-delivery. Meanwhile, we describe the application status and development prospect of nanoplatforms for nasal vaccine administration. Development of nanoplatforms for vaccine delivery via nasal route will facilitate large-scale and faster global vaccination, helping to address the threat of epidemics.

Nanoparticles for Chemoimmunotherapy Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) exhibits high recurrence and mortality rates because of the lack of effective treatment targets. Surgery and traditional chemotherapy are the primary treatment options. Immunotherapy shows high potential for treating various cancers but exhibits limited efficacy against TNBC as a monotherapy. Chemoimmunotherapy has broad prospects for applications for cancer treatment conferred through the synergistic immunomodulatory and anti-tumor effects of chemotherapy and immunotherapeutic strategies. However, improving the efficacy of synergistic therapy and reducing the side effects of multiple drugs remain to be the main challenges in chemoimmunotherapy against TNBC. Nanocarriers can target both cancer and immune cells, promote drug accumulation, and show minimal toxicity, making them ideal delivery systems for chemotherapeutic and immunotherapeutic agents. In this review, we introduce the immunomodulatory effects of chemotherapy and combined mechanisms of chemoimmunotherapy, followed by a summary of nanoparticle-mediated chemoimmunotherapeutic strategies used for treating TNBC. This up-to-date synthesis of relevant findings in the field merits contemplation, while considering avenues of investigation to enable advances in the field.

The Potential Of Antisense Oligonucleotides (ASO) Through Inhalation Based On Gold Nanoparticle (AuNP) Delivery System In Inhibiting SARS-CoV-2 Replication And Transcription

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This virus infects the respiratory, digestive, and nervous systems with a rapid transmission and a fairly high mortality rate. However, there has been no specific therapy to treat COVID-19. Previous studies have shown that antisense oligonucleotide (ASO) has good efficacy in DNA and RNA viral infections. This literature review aims to investigate the potential of inhaled ASO based on gold nanoparticles (AuNp) delivery system in inhibiting the replication and transcription of SARS-CoV-2. Literature searching using several databases, such as Google Scholar, Science Direct, ResearchGate, and NCBI. Inclusion and exclusion criteria are used to eliminate the journals that does not match the criteria, thus 28 journals are obtained. The results show that ASO has the potential to inhibit the replication and transcription of the SARS-CoV-2 virus through different mechanisms by binding to the target RNA and modulating the viral protein synthesis. One form of ASO modification that is often used is LNA GapmeR. LNA GapmeR stimulates viral RNA cleavage and can be administered by inhalation with nebulized ASO solution. AuNP as an ASO delivery system through inhalation can reduce toxicity and increase ASO concentrations in reaching target cells. Therefore, ASO therapy with AuNP through inhalation needs to be considered for COVID-19 treatment. Further clinical study about the ideal delivery system and optimal dosage of ASO based AuNP via inhalation for COVID-19 are needed to investigate soon.

Hydrogels assembled from hybrid of whey protein amyloid fibrils and gliadin nanoparticles for curcumin loading: Microstructure, tunable viscoelasticity, and stability.

Food grade hydrogel has become an ideal delivery system for bioactive substances and attracted wide attention. Hybrids of whey protein isolate amyloid fibrils (WPF) and gliadin nanoparticles (GNP) were able to assemble into WPF-GNP hydrogel at a low protein concentration of 2 wt%, among which WPF and GNP were fabricated from the hydrolysis of whey protein isolate under 85°C water bath (pH 2.0) and antisolvent precipitation, respectively. Atomic force microscope (AFM) images indicated that the ordered nanofibrillar network of WPF was formed at pH 2.0 with a thickness of about 10 nm. Cryo-SEM suggested that WPF-GNP hydrogel could arrest GNP within the fibrous reticular structure of the partially deformed WPF, while the hybrids of native whey protein isolate (WPI) and GNP (WPI-GNP hybrids) only led to protein aggregates. WPF-GNP hydrogel formed at pH 4.0 (85°C, 3 h, WPF:GNP = 4:1) possessed the largest elastic modulus (G’ = 419 Pa), which far exceeded the elastic modulus of the WPI-GNP hybrids (G’ = 16.3 Pa). The presence of NaCl could enhance the strength of WPF-GNP hydrogel and the largest value was achieved at 100 mM NaCl (∼105 mPa) in the range of 0∼500 mM due to electrostatic screening. Moreover, WPF-GNP hydrogel showed a high encapsulation efficiency for curcumin, 89.76, 89.26, 89.02, 85.87, and 79.24% for pH 2.0, 3.0, 4.0, 5.0, and 6.0, respectively, which suggested that the formed hydrogel possess good potential as a delivery system. WPF-GNP hydrogel also exhibited a good protection effect on the photodegradation stability of the loaded curcumin with the retention of up to 75.18% after hydrogel was exposed to ultraviolet radiation for 7 days. These results suggested that the viscoelasticity of WPF-GNP hydrogel was tunable via pH-, ion-, or composition-adjustment and the hydrogel showed excellent protection on the thermal and photodegradation stability of curcumin.

Dissolving microneedles: Applications and growing therapeutic potential.

Microneedles are a rapidly developing method for the transdermal delivery of therapeutic compounds. All types of microneedles, whether solid, hollow, coated, or dissolving function by penetrating the stratum corneum layer of the skin producing a microchannel through which therapeutic agents may be delivered. To date, coated and hollow microneedles have been the most successful, despite suffering from issues such as poor drug loading capabilities and blocked pores. Dissolving microneedles, on the other hand, have superior drug loading as well as other positive attributes that make it an ideal delivery system, including simple methods of fabrication and disposal, and abundantly available materials. Indeed, dissolvable microneedles can even be fabricated entirely from the therapeutic agent itself thus eliminating the requirement for additional excipients. This focused review presents the recent developments and trends of dissolving microneedles as well as potential future directions. The advantages, and disadvantages of dissolving microneedles as well as fabrication materials and methods are discussed. The potential applications of dissolving microneedles as a drug delivery system in different therapeutic areas in both research literature and clinical trials is highlighted. Applications including the delivery of cosmetics, vaccine delivery, diagnosis and monitoring, cancer, pain and inflammation, diabetes, hair and scalp disorders and inflammatory skin diseases are presented. The current trends observed in the microneedle landscape with particular emphasis on contemporary clinical trials and commercial successes as well as barriers impeding microneedle development and commercialisation are also discussed.

Functional Thermoresponsive Hydrogel Molecule to Material Design for Biomedical Applications.

Temperature-induced, rapid changes in the viscosity and reproducible 3-D structure formation makes thermos-sensitive hydrogels an ideal delivery system to act as a cell scaffold or a drug reservoir. Moreover, the hydrogels’ minimum invasiveness, high biocompatibility, and facile elimination from the body have gathered a lot of attention from researchers. This review article attempts to present a complete picture of the exhaustive arena, including the synthesis, mechanism, and biomedical applications of thermosensitive hydrogels. A special section on intellectual property and marketed products tries to shed some light on the commercial potential of thermosensitive hydrogels.

Unmet needs in glaucoma therapy: The potential role of hydrogen sulfide and its delivery strategies.

Glaucoma is an optic neuropathy disorder marked by progressive degeneration of the retinal ganglion cells (RGC). It is a leading cause of blindness worldwide, prevailing in around 2.2% of the global population. The hallmark of glaucoma, intraocular pressure (IOP), is governed by the aqueous humor dynamics which plays a crucial role in the pathophysiology of the diesease. Glaucomatous eye has an IOP of more than 22 mmHg as compared to normotensive pressure of 10-21 mmHg. Currently used treatments focus on reducing the elevated IOP through use of classes of drugs that either increase aqueous humor outflow and/or decrease its production. However, effective treatments should not only reduce IOP, but also offer neuroprotection and regeneration of RGCs. Hydrogen Sulfide (H2S), a gasotransmitter with several endogenous functions in mammalian tissues, is being investigated for its potential application in glaucoma. In addition to decreasing IOP by increasing aqueous humor outflow, it scavenges reactive oxygen species, upregulates the cellular antioxidant glutathione and protects RGCs from excitotoxicity. Despite the potential of H2S in glaucoma, its delivery to anterior and posterior regions of the eye is a challenge due to its unique physicochemical properties. Firstly, development of any delivery system should not require an aqueous environment since many H2S donors are susceptible to burst release of the gas in contact with water, causing potential toxicity and adverse effects owing to its inherent toxicity at higher concentrations. Secondly, the release of the gas from the donor needs to be sustained for a prolonged period of time to reduce dosing frequency as per the requirements of regulatory bodies. Lastly, the delivery system should provide adequate bioavailability throughout its period of application. Hence, an ideal delivery system should aim to tackle all the above challenges related to barriers of ocular delivery and physicochemical properties of H2S itself. This review discusses the therapeutic potential of H2S, its delivery challenges and strategies to overcome the associated chalenges.

ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-β (TGF-β), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-β expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation.ResultsWe synthesized DMF-loaded ROS-responsive DSPE-TK-PEG@DMF liposomes (DTP@DMF NPs). DTP@DMF NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while DTP@DMF NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that DTP@DMF NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-β and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, DTP@DMF NPs treatment presented enhanced antifibrotic effect. DTP@DMF NPs also had a prolonged residence time in the lung as well as excellent biocompatibility.ConclusionsDTP@DMF NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12951-022-01435-4.

Multifunctional manganese-containing vaccine delivery system Ca@MnCO3/LLO for tumor immunotherapy.

The ideal vaccine delivery systems can not only deliver antigens in intelligent manners but also act as adjuvants. Recently found that Mn2+ can effectively stimulate anti-tumor immune responses, and Ca2+ can regulate autophagy to promote the cross-presentation of antigens. Thus, we constructed such a manganese-containing multimode vaccine delivery system by using calcium-doped manganese carbonate microspheres (Ca@MnCO3) and perforin-listeria hemolysin (LLO), as termed as Ca@MnCO3/LLO. The two components Ca@MnCO3 and LLO, not only act as vaccine adjuvants by themselves, but also contribute to achieve cellular immunity. Among them, Ca@MnCO3 microspheres as an excellent Mn2+ and Ca2+ reservoir, can continuously release adjuvants Mn2+ and Ca2+ to enhance immune response in dendritic cells, while LLO can contribute to induce lysosomal escape. Particularly, Ca2+ was added firstly to MnCO3 microspheres to improve the stability and load capacity of the microspheres. Along with the degradation of intracellular Ca@MnCO3 microspheres, and the lysosomal membrane-lytic effects of perforin LLO, the Mn2+, Ca2+ and OVA were released to the cytoplasm. These outcomes cooperatively promote antigen cross-presentation, elicit CD8+ T cell proliferation, and finally achieve prominent anti-tumor effects. The results indicate that the manganese-containing vaccine delivery system Ca@MnCO3/LLO provides a promising platform for the construction of tumor vaccines.

Design and Fabrication of Polymeric Hydrogel Carrier for Nerve Repair.

Nerve regeneration and repair still remain a huge challenge for both central nervous and peripheral nervous system. Although some therapeutic substances, including neuroprotective agents, clinical drugs and stem cells, as well as various growth factors, are found to be effective to promote nerve repair, a carrier system that possesses a sustainable release behavior, in order to ensure high on-site concentration during the whole repair and regeneration process, and high bioavailability is still highly desirable. Hydrogel, as an ideal delivery system, has an excellent loading capacity and sustainable release behavior, as well as tunable physical and chemical properties to adapt to various biomedical scenarios; thus, it is thought to be a suitable carrier system for nerve repair. This paper reviews the structure and classification of hydrogels and summarizes the fabrication and processing methods that can prepare a suitable hydrogel carrier with specific physical and chemical properties. Furthermore, the modulation of the physical and chemical properties of hydrogels is also discussed in detail in order to obtain a better therapeutic effect to promote nerve repair. Finally, the future perspectives of hydrogel microsphere carriers for stroke rehabilitation are highlighted.

Glycated α-lactalbumin based micelles for quercetin delivery: Physicochemical stability and fate of simulated digestion.

Glycated protein is a kind of promising material that can improve the bioavailability of bioactive compounds and achieve sustained release under digestion. In this study, the α-lactalbumin (ALA)-dextran conjugates synthesized by Maillard reaction were fabricated to load and protect quercetin. Quercetin-loaded micelles stabilized by the ALA-dextran conjugates 1:4 showed the smallest size (428.57±5.64nm) with highest encapsulation efficiency (94.38%±0.50%) of quercetin. Compared to ALA/dextran mixture complex, the conjugates-based micelles had better pH, ionic strength and photothermal stability. Furthermore, the micelles composed of the conjugates 1:2 and 1:4 showed the best controlled release effect during the simulated digestion, releasing 62.41% and 66.15% of quercetin from the total encapsulated contents, respectively, which was mainly related to the resistance of glycated ALA to the enzymes. The findings indicated that ALA-dextran conjugates could be effectively designed for the ideal delivery system of hydrophobic bioactive compounds in food industry.

Multifunctional inverse opal film as a responsive drug carrier for spinal cord injury repair

An excellent drug delivery system is particularly important in trauma repair, especially for chronic hard-healing trauma, such as spinal cord injury (SCI). The SCI is difficult to repair as it is heavily influenced by inflammatory cell infiltration, neuronal axon rupture, and signal transmission interruption. Here, we present a stretched inverse opal film (SIOF) as a responsive drug carrier to deliver fibroblast growth factor 10 (FGF10) and chloroquine phosphate (CQ) for SCI repair. The SIOF was prepared by negatively replicating the silica nanospheres crystal array and was stretched to six times its original length. Benefiting from the elaborate interconnected nanopores of the SIOF, the temperature-sensitive hydrogel can host the black phosphorous quantum dots (BPQDs), and the two drugs (CQ and FGF 10) (Drugs-Gel@SIOF) for SCI repair. The excellent photothermal effect of BPQDs under the near-infrared (NIR) irradiation serves to regulate the release of drugs from the Drugs-Gel@SIOF. Furthermore, the SIOF has high biocompatibility and a special surface topology that orientates cell growth and promotes cytoskeleton elongation. The Drugs-Gel@SIOF showed an excellent effect of inhibiting inflammation and promoting axon growth. The practical performance of the Drugs-Gel@SIOF in promoting the recovery of motor function had been demonstrated by treating the spinal cord trauma rat model. These results indicate that this SIOF is an ideal intelligent delivery system with great potentials in nerve repair.

Memory amelioration by hesperidin conjugated gold nanoparticles in diabetes induced cognitive impaired rats

Cognitive deficit or dementia is one of the challenging conditions among silver citizens globally. Many life style disease conditions lead to mild or chronic cognitive deficit which later develops to Alzheimer's disease. Hesperidin is a neuroprotective with low bioavailability. Gold nanoparticles are an ideal delivery system for drug delivery to brain due to low toxicity and biocompatibility. The present research work was designed to formulate hesperidin gold nanoparticles (HSP-AuNPs) to increase its availability and to study its potency and efficacy for memory enhancement in diabetic in-vivo rat model. The synthesis of HSP-AuNPs were achieved by chemical reduction method and characterized by different spectroscopic and microscopic methods. The memory enhancement study included in-vivo study of diabetes induced cognitive impairment model, in vivo, in vitro antioxidant and histopathological studies. The cognitive and memory performances were evaluated by neuropharmacological assessment (Y-maze, elevated plus maze and radial plus maze). Further, in vitro antioxidant study was evaluated by DPPH free radical scavenging activity of HSP-AuNPs and the in vivo antioxidant assessment were performed by estimation of SOD, MDA, CAT and GSH. Both in vitro and in vivo antioxidant studies of HSP–AuNPs showed significant (p < 0.05) antioxidant activity with increased levels of SOD, CAT, GSH and decreased level of MDA as compared to free hesperidin. Histopathological studies of different organs revealed the protective actions of HSP–AuNPs in brain, pancreas and kidney. Therefore, the present study demonstrated the increase in availability of hesperidin in gold nanoparticle formulation in brain with enhanced potency and efficacy in the prevention of cognitive impairment in diabetes induced rat model by antioxidant activity.

Biofabricated nanoparticles: Their delivery and utility in Plutella xylostella management

The diamondback moth (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae) is one of the most serious cosmopolitan pests of cruciferous plants. It causes severe damage to crop quality and production, with estimated global losses of 20-40% per year. Consumer preference regarding pest-free and uncontaminated crop, unavailability of highly competitive natural enemies as well as migratory nature of DBM has obligated for the mandatory use of insecticides. The over reliance and indiscriminate use of chemical insecticides to control DBM has lead to development of resistance against almost all the modern insecticides. In addition, it has also developed resistance against most of the Bt strain. To overcome the problem of resistance, there is an urgent need for new and highly efficient method to control DBM which must be eco-friendly, cost effective and has minimum impact on the environment. One of such alternatives is nanotechnology which fulfil all the criteria to become an ideal insecticide or delivery system for insect pest management especially DBM. Nanotechnology offers great improvement in the field of pesticides as it is less toxic, shelf-life enhancement and higher water solubility. Loading of Indoxacarb on nanoparticles are reported to be highly effective they suppressed the activity of detoxification enzymes such as GST, CarE, and P450. Green synthesis of AgNPs, Single walled carbon nano tube (SWCNT) also exhibits larvicidal and pupicidal effect. These are also reported to adversely affect food consumption, growth, pupation and fecundity of P. xylostella.These nanoparticles have been found to be more stable, also the controlled release of active ingredient for a long time and provides target specific control of P. xylostella for solving adverse situations ofthe crop fields like less food security, lesser food productivity and environmental imbalance.

Enteric Coated Oral Delivery of Hydroxyapatite Nanoparticle for Modified Release Vitamin D3 Formulation

Vitamin D3 (VD) and calcium phosphate play a vital role in bone homeostasis. Factors such as obesity or gastrointestinal problems can render the use of pure VD and calcium phosphate supplements ineffective. This study investigated the possibility of using VD-loaded hydroxyapatite nanoparticles for the codelivery of VD and Ca3(PO4)2. Due to the high affinity of Ca3(PO4)2 for bone tissue, HA is an ideal delivery system to deliver VD to target tissue. Herein, HA nanoparticles were synthesized and loaded with VD using a vacuum evaporation method. The synthesized HA-VD nanoparticles were morphologically and chemically characterized by SEM, FTIR, and TGA. The system exhibited a two-stage release pattern, which includes a first-day burst release (35%) and sustained release for a further ten days. The cytocompatibility and cell penetrative ability of the nanoparticle system were assessed in vitro using preosteoblast cells: the system is nontoxic and well-tolerated. Finally, the VD-loaded HA nanoparticles were coated with a gastroresistant polymer, hypromellose phtalate-55 (HP-55) in order to protect the pH-sensitive HA from degradation at lower pHs. A coaxial electrospray technique was employed to achieve this. In all, the tested HA-VD system is a viable alternative for codelivery of VD, Ca2+, and PO43- to their target tissues.

Development and evaluation of Panax notoginseng saponins contained in an in situ pH-triggered gelling system for sustained ocular posterior segment drug delivery

Abstract Objective: This study aimed to lay the foundation for the research on Panax notoginseng saponins (PNS) in pH-sensitive in situ gel and the development and improvement of related preparations. Methods: We used Carbopol®940, a commonly used pH-sensitive polymer, and the thickener hydroxypropyl methylcellulose (HPMC E4M) as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS. In addition, formula optimization was performed by assessing gelling capability with the results of in vitro release studies. In vitro (corneal permeation, rheological, and stability) and in vivo (ocular irritation and preliminary pharmacokinetics in the vitreous) studies were also performed. Results: The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug, making it an ideal ocular delivery system for improving posterior ocular bioavailability. Conclusions: This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations. It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.

Application value and challenge of traditional Chinese medicine carried by ZIF-8 in the therapy of ischemic stroke.

Stroke is a group of major diseases that cause death or disability in adults, with high incidence and lack of available therapeutic strategies. Although traditional Chinese medicine (TCM) has continuously achieved good effects in the therapy of stroke while there is still not convincing due to the limitation of blood-brain permeability, as well as the individual differences in usage and dosage. With the improvement of nanotechnology, TCM nanopreparation has gradually become a research hotspot in various fields due to its advantages in permeating the blood-brain barrier, targeting delivery, enhancing sustained-release drug delivery, changing the distribution in the body, and improving bioavailability. Zeolitic imidazolate framework-8 (ZIF-8) is an ideal nano-drug delivery system for adsorption, catalysis, and drug loading, which is a biocompatible metal-organic framework framed by 2-methylimidazole and zinc ions. At present, ZIF-8 was wildly used in the treatment of ischemic stroke. However, challenges remain persists for its clinical application, such as preparation technology, detection technology in vivo, targeting specificity, safety and stability, and so forth. Therefore, more efforts need to overcome the above problems to develop the application of TCM nanopreparations in the therapy of ischemia/reperfusion in the future.