Nanocarrier-based Delivery Systems Research Articles

Advances in Chronic Wound Management: From Conventional Treatment to Novel Therapies and Biological Dressings.

Chronic wounds can be classified as diabetic foot ulcers, pressure ulcers, or venous leg ulcers. Chronic wound management has become a threat to clinicians and constitutes a major healthcare burden. The healing process of chronic wounds requires many factors to work in concert to achieve optimal healing. Various treatment options, ranging from hypoxia to infection, have evolved considerably to address the challenges associated with chronic wound healing. The conventional and accelerating treatments for chronic wounds still represent an unmet medical need due to the complex pathophysiology of the chronic wound microenvironment. In clinical settings, traditional chronic wound care practices rely on nonspecific topical treatment, which can reduce pain and alleviate disease progression with varying levels of success but fail to completely cure the wounds. Conventional wound dressings, such as hydrocolloids, gauze, foams, and films, have also shown limited success for the treatment of chronic wounds and only act as a physical barrier and absorb wound exudates. Emerging advances in treatment approaches, including novel therapies (stem cells, microRNAs, and nanocarrier-based delivery systems) and multifunctional biological dressings, have been reported for chronic wound repair. This review summarizes the challenges offered by chronic wounds and discusses recent advancements in chronic wound treatment.

Azadirachta indica Biopesticide: A Sustainable Alternative to Synthetic Chemicals in Pest Control (A Review)

Over time, heavy reliance on synthetic pesticides to combat phytophagous insects has led to their accumulation in the environment, resulting in increased pest resistance and reduced soil biodiversity. Approximately 90% of these pesticides enter various environmental systems through runoff, posing significant health risks to both farmers and consumers. Thus, there’s a growing need for eco-friendly alternatives to establish effective pest management while reducing health hazards. One such approach involves harnessing Azadirachta indica, commonly known as the neem plant, which contains agro-medicinal components with insecticidal, immunomodulatory, and anti-cancer properties. Azadirachtin, a key ingredient, acts as an insect deterrent, disrupts reproduction, and enhances pest control through innovative nanocarrier-based delivery systems, ensuring stability and sustainability. In this review, we examine the essential components of neem with pesticidal properties, explore their active functional ingredients, and investigate the utilization of nanocarriers for controlled release, thereby enhancing stability and sustainability.

Cannabidiol-Loaded Nanocarriers and Their Therapeutic Applications.

Cannabidiol (CBD), one of the most promising constituents isolated from Cannabis sativa, exhibits diverse pharmacological actions. However, the applications of CBD are restricted mainly due to its poor oral bioavailability. Therefore, researchers are focusing on the development of novel strategies for the effective delivery of CBD with improved oral bioavailability. In this context, researchers have designed nanocarriers to overcome limitations associated with CBD. The CBD-loaded nanocarriers assist in improving the therapeutic efficacy, targetability, and controlled biodistribution of CBD with negligible toxicity for treating various disease conditions. In this review, we have summarized and discussed various molecular targets, targeting mechanisms and types of nanocarrier-based delivery systems associated with CBD for the effective management of various disease conditions. This strategic information will help researchers in the establishment of novel nanotechnology interventions for targeting CBD.

Potentials of Polymeric Nanocarriers Loaded with Clarithromycin for Antibacterial Activity

Clarithromycin (CTM) is a semisynthetic derivative of erythromycin that have been reported to exhibit potential antibiotic activities mostly against the gram-negative and gram-positive bacteria, lower/upper respiratory tract and skin infection causing pathogens. It is widely used for the prevention and management of infections due to Mycobacterium avium complexes and peptic ulcers due to Helicobacter pylori. Various marketed formulation of CTM in the form of tablets, capsules and other conventional dosage forms is available as anti-infective, however the drug itself has several limitations. These limitations include low oral bioavailability, rapid metabolism, poor targeting to infected sites and toxicity to normal cells/tissues. Also, the CTM-based therapy has been reported for several gastrointestinal adverse effects, including diarrhea, stomach upset, gastric distress, atypical taste, and others. Thus, to overcome these issue, various novel strategies including nanotechnology or nanocarrier-based approaches have showed significant effects and have been immensely considered worldwide. In recent years, the various nanocarriers or nanocarrier-based delivery systems, particularly the polymeric nanocarrier have played significant role in effective drug targeting. Thus, in this review, the various polymeric nanocarrier-based delivery systems of CTM that effective reduced the dosing frequency, improved the patient compliance and potentially enhanced the therapeutic efficiency of CTM has been summarized.

Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process

Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.

Construction and application of star polycation nanocarrier-based microRNA delivery system in Arabidopsis and maize

BackgroundMicroRNA (miRNA) plays vital roles in the regulation of both plant architecture and stress resistance through cleavage or translation inhibition of the target messenger RNAs (mRNAs). However, miRNA-induced gene silencing remains a major challenge in vivo due to the low delivery efficiency and instability of miRNA, thus an efficient and simple method is urgently needed for miRNA transformation. Previous researches have constructed a star polycation (SPc)-mediated transdermal double-stranded RNA (dsRNA) delivery system, achieving efficient dsRNA delivery and gene silencing in insect pests.ResultsHere, we tested SPc-based platform for direct delivery of double-stranded precursor miRNA (ds-MIRNA) into protoplasts and plants. The results showed that SPc could assemble with ds-MIRNA through electrostatic interaction to form nano-sized ds-MIRNA/SPc complex. The complex could penetrate the root cortex and be systematically transported through the vascular tissue in seedlings of Arabidopsis and maize. Meanwhile, the complex could up-regulate the expression of endocytosis-related genes in both protoplasts and plants to promote the cellular uptake. Furthermore, the SPc-delivered ds-MIRNA could efficiently increase mature miRNA amount to suppress the target gene expression, and the similar phenotypes of Arabidopsis and maize were observed compared to the transgenic plants overexpressing miRNA.ConclusionTo our knowledge, we report the first construction and application of star polycation nanocarrier-based platform for miRNA delivery in plants, which explores a new enable approach of plant biotechnology with efficient transformation for agricultural application.Graphical

Identification of the fibroin of Stigmaeopsis nanjingensis by a nanocarrier-based transdermal dsRNA delivery system

Stigmaeopsis nanjingensis (Ma and Yuan) (Acari: Tetranychidae) is an important pest of bamboo—feeding behavior and silk production by the female adult mites is seriously harmful to bamboo leaves. Due to its small size, silking and cocooning, its management is difficult. This study discusses a fast and easy method for management of the pest by disturbing the spinning behavior. Stigmaeopsis nanjingensis is host specific and feeds only on bamboo leaves. Leaf margins of bamboo are highly hydrophobic, which makes dsRNA difficult to immerse. Hence, it is a challenge to apply the commonly used feeding method to inhibit gene expression in mites. In this study, we deliver dsRNA to interfere with the expression of fibroin by body wall permeation with a nanocarrier-based delivery system. The dsRNA/nanocarrier formulation droplets could enter the body cavity within 2 min after falling on the mite. The fibroin silencing efficiency was 75.4%, and the results of electron microscopy showed that dsRNA/nanocarrier damage the morphological structure of the silk thread. This study demonstrated the effectiveness of a nanocarrier-based percutaneous dsRNA delivery system in S. nanjingensis and its effect on the fibroin gene that influences the spinning behavior of S. nanjingensis. These findings may provide a new delivery system for RNAi-based control of spider mites that utilize protective webbing in the field.

Potential of Nanocarrier-Based Drug Delivery Systems for Brain Targeting: A Current Review of Literature.

The advent of nanotechnologies such as nanocarriers and nanotherapeutics has changed the treatment strategy and developed a more efficacious novel drug delivery system. Various drug delivery systems are focused on drug-targeting of brain cells. However, the manifestation of the brain barrier is the main hurdle for the effective delivery of chemotherapeutics, ultimately causing treatment failure of various drugs. To solve this problem, various nanocarrier-based drug delivery system has been developed for brain targeting. This review outlines nanocarrier-based composites for different brain diseases and highlights nanocarriers for drug targeting towards brain cells. It also summarizes the latest developments in nanocarrier-based delivery systems containing liposomal systems, dendrimers, polymeric micelles, polymeric nanocarriers, quantum dots (QDs), and gold nanoparticles. Besides, the optimal properties of nanocarriers and therapeutic implications for brain targeting have been extensively studied. Finally, the potential applications and research opportunities for nanocarriers in brain targeting are discussed.

Nano-Medicines a Hope for Chagas Disease!

Chagas disease, is a vector-mediated tropical disease whose causative agent is a parasitic protozoan named Trypanosoma cruzi. It is a very severe health issue in South America and Mexico infecting millions of people every year. Protozoan T. cruzi gets transmitted to human through Triatominae, a subfamily of the Reduviidae, and do not have any effective treatment or preventative available. The lack of economic gains from this tropical parasitic infection, has always been the reason behind its negligence by researchers and drug manufacturers for many decades. Hence there is an enormous requirement for more efficient and novel strategies to reduce the fatality associated with these diseases. Even, available diagnosis protocols are outdated and inefficient and there is an urgent need for rapid high throughput diagnostics as well as management protocol. The current advancement of nanotechnology in the field of healthcare has generated hope for better management of many tropical diseases including Chagas disease. Nanoparticulate systems for drug delivery like poloxamer coated nanosuspension of benzimidazole have shown promising results in reducing toxicity, elevating efficacy and bioavailability of the active compound against the pathogen, by prolonging release, thereby increasing the therapeutic index. Moreover, nanoparticle-based drug delivery has shown promising results in inducing the host’s immune response against the pathogen with very few side effects. Besides, advances in diagnostic assays, such as nanosensors, aided in the accurate detection of the parasite. In this review, we provide an insight into the life cycle stages of the pathogen in both vertebrate host and the insect vector, along with an overview of the current therapy for Chagas disease and its limitations; nano carrier-based delivery systems for antichagasic agents, we also address the advancement of nano vaccines and nano-diagnostic techniques, for treatment of Chagas disease, majorly focusing on the novel perspectives in combating the disease.

Versatile delivery systems for non-platinum metal-based anticancer therapeutic agents

• Non-Pt metal-based compounds have great potential as anticancer agents. • Versatile delivery systems were designed to deliver non-Pt metal-based compounds. • Multifunctional nano-drug delivery systems are very useful for cancer treatment. Platinum-based anticancer drugs currently available in the market are associated with severe side effects. Therefore, extensive research has been performed to design and synthesize non-platinum metal coordination compounds, while their delivery using nanocarriers has attracted particular interest, providing encouraging results. In this review, coordination compounds based on ruthenium, copper, gold, iridium, palladium, zinc, etc. have received reasonable attention as anticancer agents. Moreover, we summarize the advances reported in the last decade in the design of various nanocarrier types, such as carbon-, amphiphilic copolymer-, polysaccharide-, and protein- or peptide-based nanocarriers, as well as inorganic nanoparticles and metal–organic frameworks, for the delivery of ruthenium-, copper-, gold-, iridium-, palladium- and zinc-based compounds. The delivery of other non-platinum metal-based compounds, the main challenges and future prospects in this field are also discussed. We expect that the future direction of nanocarrier-based delivery systems for non-platinum metal anticancer compounds will lead to a new generation in anticancer medicine.

Nanocarriers-Mediated Drug Delivery Systems for Anticancer Agents: An Overview and Perspectives.

Nanotechnology has been actively integrated as drug carriers over the last few years to treat various cancers. The main hurdle in the clinical management of cancer is the development of multidrug resistance against chemotherapeutic agents. To overcome the limitations of chemotherapy, the researchers have been developing technological advances for significant progress in the oncotherapy by enabling the delivery of chemotherapeutic agents at increased drug content levels to the targeted spots. Several nano-drug delivery systems designed for tumor-targeting are evaluated in preclinical and clinical trials and showed promising outcomes in cancerous tumors’ clinical management. This review describes nanocarrier’s importance in managing different types of cancers and emphasizing nanocarriers for drug delivery and cancer nanotherapeutics. It also highlights the recent advances in nanocarriers-based delivery systems, including polymeric nanocarriers, micelles, nanotubes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and quantum dots (QDs). The nanocarrier-based composites are discussed in terms of their structure, characteristics, and therapeutic applications in oncology. To conclude, the challenges and future exploration opportunities of nanocarriers in chemotherapeutics are also presented.

Resveratrol: nanocarrier-based delivery systems to enhance its therapeutic potential.

Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic compound existing in trees, peanuts and grapes and exhibits a broad spectrum of promising therapeutic activities, but it is unclear whether this entity targets the sites of action after oral administration. In vivo applicability of resveratrol has limited success so far, mainly due to its incompetent systemic delivery resulting from its low water solubility, poor bioavailability and short biological half-life. First-pass metabolism and presence of enterohepatic recirculation create doubt on the biological application of high doses typically used for in vitro trials. To augment bioavailability, absorption and uptake of resveratrol by cellular internalization, countless approaches have been implemented which involve the use of nanocarriers. Nanocarriers are a well-known delivery system used to reduce first-pass hepatic metabolism, overcome enterohepatic recirculation and accelerate the absorption of drugs via lymphatic pathways.

Nanotherapies for the Treatment of Age-Related Macular Degeneration (AMD) Disease: Recent Advancements and Challenges.

Age-related Macular Degeneration (AMD) is one of the common diseases affecting the posterior part of the eye, of a large population above 45 years old. Anti-Vascular Endothelial Growth Factor- A (Anti-VEGF-A) agents have been considered and approved as therapeutic agents for the treatment of AMD. Due to the large molecular weight and poor permeability through various eye membranes, VEGF-A inhibitors are given through an intravitreal injection, even though the delivery of small therapeutic molecules by topical application to the posterior part of the eye exhibits challenges in the treatment. To overcome these limitations, nanocarrier based delivery systems have been utilized to a large extent for the delivery of therapeutics. Nanocarriers system offers prodigious benefits for the delivery of therapeutics to the posterior part of the eye in both invasive and non-invasive techniques. The nano size can improve the permeation of therapeutic agent across the biological membranes. They provide protection from enzymes present at the site, targeted delivery or binding with the disease site and extend the release of therapeutic agents with prolonged retention. This leads to improved therapeutic efficacy, patient compliance, and cost effectiveness of therapy with minimum dose associated side-effects. This review has summarized various nanocarriers explored for the treatment of AMD and challenges in translation.

Nanocarriers for the Delivery of Medical, Veterinary, and Agricultural Active Ingredients.

Nanocarrier-based delivery systems can be used to increase the safety and efficacy of active ingredients in medical, veterinary, or agricultural applications, particularly when such ingredients are unstable, sparingly soluble, or cause off-target effects. In this review, we highlight the diversity of nanocarrier materials and their key advantages compared to free active ingredients. We discuss current trends based on peer-reviewed research articles, patent applications, clinical trials, and the nanocarrier formulations already approved by regulatory bodies. Although most nanocarriers have been engineered to combat cancer, the number of formulations developed for other purposes is growing rapidly, especially those for the treatment of infectious diseases and parasites affecting humans, livestock, and companion animals. The regulation and prohibition of many pesticides have also fueled research to develop targeted pesticide delivery systems based on nanocarriers, which maximize efficacy while minimizing the environmental impact of agrochemicals.

Nanoparticles and Vaccine Development.

In spite of the progress of conventional vaccines, improvements are required due to concerns about the low immunogenicity of the toxicity, instability, and the need for multiple administrations of the vaccines. To overcome the mentioned problems, nanotechnology has recently been incorporated into vaccine development. Nanotechnology increasingly plays an important role in vaccine development nanocarrier-based delivery systems that offer an opportunity to increase the cellular and humoral immune responses. The use of nanoparticles in vaccine formulations allows not only enhanced immunogenicity and stability of antigen, but also targeted delivery and slow release. Over the past decade, nanoscale size materials such as virus-like particles, liposomes, ISCOMs, polymeric, inorganic nanoparticles and emulsions have gained attention as potential delivery vehicles for vaccine antigens, which can both stabilize vaccine antigens and act as adjuvants. This advantage is attributable to the nanoscale particle size, which facilitates uptake by Antigen- Presenting Cells (APCs), then leading to efficient antigen recognition and presentation. Modifying the surfaces of nanoparticles with different targeting moieties permits the delivery of antigens to specific receptors on the cell surface, thereby stimulating selective and specific immune responses. This review provides an overview of recent advances in nanovaccinology.

Advances in nanocarriers as drug delivery systems in Chagas disease.

Chagas disease is one of the most important public health problems in Latin America due to its high mortality and morbidity levels. There is no effective treatment for this disease since drugs are usually toxic with low bioavailability. Serious efforts to achieve disease control and eventual eradication have been unsuccessful to date, emphasizing the need for rapid diagnosis, drug development, and a reliable vaccine. Novel systems for drug and vaccine administration based on nanocarriers represent a promising avenue for Chagas disease treatment. Nanoparticulate systems can reduce toxicity, and increase the efficacy and bioavailability of active compounds by prolonging release, and therefore improve the therapeutic index. Moreover, nanoparticles are able to interact with the host’s immune system, modulating the immune response to favour the elimination of pathogenic microorganisms. In addition, new advances in diagnostic assays, such as nanobiosensors, are beneficial in that they enable precise identification of the pathogen. In this review, we provide an overview of the strategies and nanocarrier-based delivery systems for antichagasic agents, such as liposomes, micelles, nanoemulsions, polymeric and non-polymeric nanoparticles. We address recent progress, with a particular focus on the advances of nanovaccines and nanodiagnostics, exploring new perspectives on Chagas disease treatment.

Nanocarrier-based systems for targeted and site specific therapeutic delivery.

Systemic drug delivery methods such as oral or parenteral administration of free drugs possess relatively low treatment efficiency and marked adverse side effects. The use of nanoparticles for drug delivery in most cases substantially enhances drug efficacy, improves pharmacokinetics and drug release and limits their side effects. However, further enhancement in drug efficacy and significant limitation of adverse side effects can be achieved by specific targeting of nanocarrier-based delivery systems especially in combination with local administration. The present review describes major advantages and limitations of organic and inorganic nanocarriers or living cell-based drug and nucleic acid delivery systems. Among these, different nanoparticles, supramolecular gels, therapeutic cells as living drug carriers etc. have emerged as a new frontier in modern medicine.

Nanoparticles for Immune Stimulation Against Infection, Cancer, and Autoimmunity.

Vaccination using nanocarrier-based delivery systems has recently emerged as a promising approach for meeting the continued challenge posed by infectious diseases and cancer. A diverse portfolio of nanocarriers of various sizes, compositions, and physical parameters have now been developed, and this diversity provides an opportunity for the rational design of vaccines that can mediate targeted delivery of various antigens and adjuvants or immune regulatory agents in ways unachievable with classical vaccination approaches. This flexibility allows control over the characteristics of vaccine-elicited immune responses such that they can be tailored to be effective in circumstances where classical vaccines have failed. Furthermore, the utility of nanocarrier-based immune modulation extends to the treatment of autoimmune disease where precisely targeted inhibition of immune responses is desirable. Clearly, the selection of appropriate nanocarriers, antigens, adjuvants, and other components underpins the efficacy of these nanoimmune interventions. Herein, we provide an overview of currently available nanocarriers of various types and their physical and pharmacological properties with the goal of providing a resource for researchers exploring nanomaterial-based approaches for immune modulation and identify some information gaps and unexplored questions to help guide future investigation.

Small Molecule Nanodrug Assembled of Dual-Anticancer Drug Conjugate for Synergetic Cancer Metastasis Therapy.

The nanocarrier-based delivery system has emerged as a promising candidate for cancer therapy; nevertheless, their quality problems, variation between batches, and carrier-related toxicity issues have restricted their clinical utilization. Compared with traditional carrier-based nanoparticles, carrier-free nanodrug delivery systems preferred to overcome all these drawbacks and will have a wide range of applications in biomedicine and nanotechnology. Herein, we developed a novel carrier-free nanodrug Asp-UA consisted of the classical drug aspirin and the natural plant drug UA via a green and simple approach. The Asp-UA NPs were investigated for shape, particle size, zeta potential, stability, and UV-vis spectroscopy absorption. Cellular uptake study showed that Asp-UA NPs could be easily internalized by HepG2 cells; cellular study demonstrated that Asp-UA NPs held better inhibitory efficiency on tumor metastasis with low toxicity in vitro and in vivo. Moreover, Asp-UA NPs could obviously suppress the progress of cancer metastasis by H22 cells in vivo. Overall, Asp-UA NPs possess a variety of advantages and hold promise to become an alternative to the treatment of cancer metastasis.

Enhanced Antitumor Effects of Epidermal Growth Factor Receptor Targetable Cetuximab-Conjugated Polymeric Micelles for Photodynamic Therapy.

Nanocarrier-based delivery systems are promising strategies for enhanced therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)—a light-triggered chemical reaction that generates localized tissue damage for disease treatments—usually has side effects, and thus patients receiving photosensitizers should be kept away from direct light to avoid skin phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225) was conjugated to the surface of methoxy poly(ethylene glycol)-b-poly(lactide) (mPEG-b-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6-loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing A431 cells observed by confocal laser scanning microscopy (CLSM), thereby decreasing the IC50 value of Ce6-mediated PDT from 0.42 to 0.173 μM. No significant differences were observed in cellular uptake study or IC50 value between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of tumor growth inhibition, TGI% = 84.8) were significantly smaller than those in the Ce6-PDT (TGI% = 38.4) and Ce6/PM-PDT groups (TGI% = 53.3) (p < 0.05) at day 21 through reduced cell proliferation in A431 xenografted mice. These results indicated that active EGFR targeting of photosensitizer-loaded micelles provides a possible way to resolve the dose-limiting toxicity of conventional photosensitizers and represents a potential delivery system for PDT in a clinical setting.