Nanocarrier-based Drug Delivery Systems Research Articles

Drug Delivery System Approaches for Rheumatoid Arthritis Treatment: A Review.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that has traditionally been treated using a variety of pharmacological compounds. However, the effectiveness of these treatments is often limited due to challenges associated with their administration. Oral and parenteral routes of drug delivery are often restricted due to issues such as low bioavailability, rapid metabolism, poor absorption, first-pass effect, and severe side effects. In recent years, nanocarrier-based delivery methods have emerged as a promising alternative for overcoming these challenges. Nanocarriers, including nanoparticles, dendrimers, micelles, nanoemulsions, and stimuli-sensitive carriers, possess unique properties that enable efficient drug delivery and targeted therapy. Using nanocarriers makes it possible to circumvent traditional administration routes' limitations. One of the key advantages of nanocarrier- based delivery is the ability to overcome resistance or intolerance to traditional antirheumatic therapies. Moreover, nanocarriers offer improved drug stability, controlled release kinetics, and enhanced solubility, optimizing the therapeutic effect. They can also protect the encapsulated drug, prolonging its circulation time and facilitating sustained release at the target site. This targeted delivery approach ensures a higher concentration of the therapeutic agent at the site of inflammation, leading to improved therapeutic outcomes. This article explores potential developments in nanotherapeutic regimens for RA while providing a comprehensive summary of current approaches based on novel drug delivery systems. In conclusion, nanocarrier-based drug delivery systems have emerged as a promising solution for improving the treatment of rheumatoid arthritis. Further advancements in nanotechnology hold promise for enhancing the efficacy and safety of RA therapies, offering new hope for patients suffering from this debilitating disease.

Assessment of nanocarrier mediated afatinib pharmacokinetic: A comparative in-vivo study in rat model for enhanced therapeutic efficacy in lung cancer management

Nanocarrier-based drug delivery systems are at the forefront of innovative research in the field of medical science, providing potential pathways for treatments across several routes of administration. Notably, a great deal of research has gone into maximizing the potential of polymeric nanoparticles and liposomes, with a focus on addressing the intricacies of lung cancer through the pulmonary route. The present research aims to improve the pharmacokinetic profile of afatinib using a liposome and polymeric nanoparticle based dry powder approach rather than the afatinib plain drug solution to increase the survival rate and improvise the treatment of patients suffering from lung cancer. Formulated afatinib encapsulated PEGylated liposomal and afatinib loaded PLGA nanoparticles dry powder inhaler were characterized for the in-vivo pulmonary pharmacokinetics study using rat model upon intratracheal administration. The results of in-vivo pulmonary pharmacokinetics studies of both formulations indicated that it improved the pharmacokinetics profiles of the encapsulated agent (afatinib) by increasing the Cmax, AUC Total, Mean residence time (MRT) and decreasing the clearance (CL), and volume of distribution (VZ) than the afatinib plain drug solution. Results suggested that the selective targeting ability of the nanocarrier system can be a favourable approach for the management of lung cancer by the inhalation route.

Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer.

Prostate cancer remains a significant global health concern, requiring innovative approaches for improved therapeutic outcomes. In recent years, nanoparticle-based drug delivery systems have emerged as promising strategies to address the limitations of conventional cancer chemotherapy. The key trends include utilizing nanoparticles for enhancing drug delivery to prostate cancer cells. Nanoparticles have some advantages such as improved drug solubility, prolonged circulation time, and targeted delivery of drugs. Encapsulation of chemotherapeutic agents within nanoparticles allows for controlled release kinetics, reducing systemic toxicity while maintaining therapeutic efficacy. Additionally, site-specific accumulation within the prostate tumor microenvironment is made possible by the functionalization of nanocarrier with targeted ligands, improving therapeutic effectiveness. This article highlights the basics of prostate cancer, statistics of prostate cancer, mechanism of multidrug resistance, targeting approach, and different types of nanocarrier used for the treatment of prostate cancer. It also includes the applications of nanocarriers for the treatment of prostate cancer and clinical trial studies to validate the safety and efficacy of the innovative drug delivery systems. The article focused on developing nanocarrier-based drug delivery systems, with the goal of translating these advancements into clinical applications in the future.

The development of nanocarriers for natural products.

Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier-based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self-assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long-term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

CURRENT PERSPECTIVES ON APPLICATIONS OF NANOPARTICLES FOR CANCER MANAGEMENT

In the realm of cancer diagnostics, imaging and therapeutics, nanocarrier-based drug delivery systems have gained extensive importance owing to their promising attributes and potential to enhance therapeutic effectiveness. The primary area of research revolves around formulating innovative intelligent nanocarriers such as nanoparticles (NPs) which are capable of selectively responding to cancer-specific conditions and efficiently delivering medications to target cells. These nanocarriers, whether operating in a passive or active manner, can transport loaded therapeutic cargos to the tumor site while minimizing drug elimination from the drug delivery systems. This review primarily focuses on presenting recent advancements in the development and utilization of nanoparticles in the treatment of various cancer types, such as pancreatic cancer, prostate cancer, colorectal cancer, cervical cancer, and breast cancer.

Recent advances in microwave-assisted nanocarrier based drug delivery system: Trends and technologies

Recent advances in microwave-assisted nanocarrier based drug delivery system: Trends and technologies

Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant Tuberculosis.

Tuberculosis (TB) is one of the most prevalent infectious diseases. The global TB situation is further complicated by increasing patient numbers infected with Mycobacterium tuberculosis (M.tb.) strains resistant to either one or two of the first-line therapeutics, promoted by insufficient treatment length and/or drug levels due to adverse reactions and reduced patient compliance. An intriguing approach to improve anti-TB therapy relates to nanocarrier-based drug-delivery systems, which enhance local drug concentrations at infection sites without systemic toxicity. Recently developed anti-TB antibiotics, however, are lipophilic and difficult to transport in aqueous systems. Here, the very lipophilic TB-antibiotics bedaquiline (BDQ) and BTZ (1,3-benzothiazin-4-one 043) are prepared as high-dose, amorphous nanoparticles via a solvent-antisolvent technique. The nanoparticles exhibit mean diameters of 60 ± 13 nm (BDQ) and 62 ± 44 nm (BTZ) and have an extraordinarily high drug load with 69% BDQ and >99% BTZ of total nanoparticle mass plus a certain amount of surfactant (31% for BDQ, <1% for BTZ) to make the lipophilic drugs water-dispersible. Suspensions with high drug load (4.1 mg/mL BDQ, 4.2 mg/mL BTZ) are stable for several weeks. In vitro and in vivo studies employing M.tb.-infected macrophages and susceptible C3HeB/FeJ mice show promising activity, which outperforms conventional BDQ/BTZ solutions (in DMF or DMSO) with an up to 50% higher efficacy upon pulmonary delivery. In vitro, the BDQ/BTZ nanoparticles demonstrate their ability to cross the different biological barriers and to reach the site of the intracellular mycobacteria. In vivo, high amounts of the BDQ/BTZ nanoparticles are found in the lung and specifically inside granulomas, whereas only low BDQ/BTZ-nanoparticle levels are observed in spleen or liver. Thus, pulmonary delivered BDQ/BTZ nanoparticles are promising formulations to improve antituberculosis treatment.

Lipid Nanocarrier-Based Drug Delivery Systems: Therapeutic Advances in the Treatment of Lung Cancer.

Although various treatments are currently being developed, lung cancer still has a very high mortality rate. Moreover, while various strategies for the diagnosis and treatment of lung cancer are being used in clinical settings, in many cases, lung cancer does not respond to treatment and presents reducing survival rates. Cancer nanotechnology, also known as nanotechnology in cancer, is a relatively new topic of study that brings together scientists from a variety of fields, including chemistry, biology, engineering, and medicine. The use of lipid-based nanocarriers to aid drug distribution has already had a significant impact in several scientific fields. Lipid-based nanocarriers have been demonstrated to help stabilize therapeutic compounds, overcome barriers to cellular and tissue absorption, and improve in vivo drug delivery to specific target areas. For this reason, lipid-based nanocarriers are being actively researched and used for lung cancer treatment and vaccine development. This review discusses the improvements in drug delivery achieved with lipid-based nanocarriers, the obstacles that still exist with in vivo applications, and the current clinical and experimental applications of lipid-based nanocarriers in lung cancer treatment and management.

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives.

Exosomes are nanosized (size ~ 30-150nm) natural vesicular structures released from cells by physiological processes or pathological circumstances. Exosomes are growing in popularity as a result of their many benefits over conventional nanovehicles, including their ability to escape homing in the liver or metabolic destruction and their lack of undesired accumulation before reaching their intended targets. Various therapeutic molecules, including nucleic acids, have been incorporated into exosomes by different techniques, many of which have shown satisfactory performance in various diseases. Surface-modified exosomes are a potentially effective strategy, and it increases the circulation time and produces the specific drug target vehicle. In this comprehensive review, we describe composition exosomes biogenesis and the role of exosomes in intercellular signaling and cell-cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research and discuss future perspectives. In addition to the current status of exosomes as a therapeutic carrier, the lacuna in the clinical development lifecycles along with the possible strategies to fill the lacuna have been addressed.

Nanocarrier-Based Drug-Delivery System in Herpes Simplex Virus Treatment

Herpes simplex virus (HSV) is a highly contagious DNA virus that affects the majority of people worldwide. HSV establishes a latent infection in the ganglia, where it can reactivate, leading to recurrent disease. Currently, there are many experimental vaccines against HSV, but none have been used to treat herpes infections. At the same time, the therapeutic effect of existing anti-HSV drugs is limited. Nanocarriers, which deliver drugs to specific targets, have been used in different diseases, including viral infections. Nanocarriers could be designed to encapsulate drugs and directly target infected cells. This review will describe in detail the use of nanocarriers for targeted therapy of HSV infection.

Capsaicin-loaded alginate nanoparticles embedded polycaprolactone-chitosan nanofibers as a controlled drug delivery nanoplatform for anticancer activity

Nanocarrier-based drug delivery systems have been designed into various structures that can effectively prevent cancer progression and improve the therapeutic cancer index. However, most of these delivery systems are designed to be simple nanostructures with several limitations, including low stability and burst drug release features. A nano-in-nano delivery technique is explored to address the aforementioned concerns. Accordingly, this study investigated the release behavior of a novel nanoparticles-in-nanofibers delivery system composed of capsaicin-loaded alginate nanoparticles embedded in polycaprolactone-chitosan nanofiber mats. First, alginate nanoparticles were prepared with different concentrations of cationic gemini surfactant and using nanoemulsion templates. The optimized formulation of alginate nanoparticles was utilized for loading capsaicin and exhibited a diameter of 19.42 ± 1.8 nm and encapsulation efficiency of 98.7 % ± 0.6 %. Likewise, blend polycaprolactone-chitosan nanofibers were prepared with different blend ratios of their solutions (i.e., 100:0, 80:20, 60:40) by electrospinning method. After the characterization of electrospun mats, the optimal nanofibers were employed for embedding capsaicin-loaded alginate nanoparticles. Our findings revealed that embedding capsaicin-loaded alginate nanoparticles in polycaprolactone-chitosan nanofibers, prolonged capsaicin release from 120 h to more than 500 h. Furthermore, the results of in vitro analysis demonstrated that the designed nanoplatform could effectively inhibit the proliferation of MCF-7 human breast cells while being nontoxic to human dermal fibroblasts (HDF). Collectively, the prepared nanocomposite drug delivery platform might be promising for the long-term and controlled release of capsaicin for the prevention and treatment of cancer.

Implementation of Quality by Design in the Formulation and Development of Nanocarrier-Based Drug Delivery Systems.

Quality by design (QbD) has recently fascinated researchers for utilizing it in various arenas of pharma trends. By overcoming the conventional process, QbD prevents the risk of errors caused by the 'guess and by god approach'. This framework fosters profound knowledge of product and process quality by implying sound science and risk assessment strategies. The virtue of QbD leads to the collaborative contribution to pharmaceutical industrialists and satisfies the regulatory bodies. Additionally, leading to rapid production, saves time and expenditure, tremendous versatility, provides immense knowledge, improves robustness, higher consistency, reduces user's dilemma, decreases certainty of failure, declining inter-batch variation in pharmaceutical development. In this ever-increasing continuous production world, regulatory organizations such as the U.S. Food & Drug Administration and the International Conference on Harmonization recommend Q8 to Q14 guidelines in order to obtain the desired quality product. This review extensively discusses on various approaches of QbD for the pharmaceutical development of nano-carrier drug delivery systems. Additionally, QbD's applications in process and analytical method development techniques are documented.

Nanocarriers in Veterinary Medicine: A Challenge for Improving Osteosarcoma Conventional Treatments.

In recent years, several nanocarrier-based drug delivery systems, such as polymeric nanoparticles, solid lipid nanoparticles, metallic nanoparticles, liposomes, and others, have been explored to target and treat a wide variety of diseases. Their employment has brought many benefits, not only to human medicine but also to veterinary medicine, albeit at a slower rate. Soon, the use of nanocarriers could revolutionize the animal health sector, and many veterinary therapies will be more effective as a result. The purpose of this review is to offer an overview of the main applications of nanocarriers in the veterinary field, from supplements for animal health and reproduction to nanovaccines and nanotherapies. Among the major pathologies that can affect animals, special attention is given to canine osteosarcoma (OSA): a comparison with human OSA is provided and the main treatment options are reviewed emphasizing the benefits that nanocarriers could bring in the treatment of this widespread disease.

Targeting nanoparticle-conjugated microbubbles combined with ultrasound-mediated microbubble destruction for enhanced tumor therapy

The stress of the abnormal stromal matrix of solid tumors is a major limiting factor that prevents drug penetration. Controlled, accurate, and efficient delivery of theranostic agents into tumor cells is crucial. Combining ultrasound with nanocarrierbased drug delivery systems have become a promising approach for targeted drug delivery in preclinical cancer therapy. In this study, to ensure effective tumor barrier penetration, access to the tumor microenvironment, and local drug release, we designed targeted nanoparticle (NP)-conjugated microbubbles (MBs); ultrasound could then help deliver acoustic energy to release the NPs from the MBs. The ultrasound-targeted MB destruction (UTMD) system of negatively charged NPs was conjugated with positively charged MBs using an ionic gelation method. We demonstrated the transfer of targeted NPs and their entry into gastric cancer cells through ligand-specific recognition, followed by enhanced cell growth inhibition owing to drug delivery-induced apoptosis. Moreover, the UTMD system combining therapeutic and ultrasound image properties can effectively target gastric cancer, thus significantly enhancing antitumor activity, as evident by tumor localization in an orthotopic mouse model of gastric cancer. The combination of ultrasound and NP-based drug delivery systems has become a promising approach for targeted drug delivery in preclinical cancer therapy.

Multifunctional bovine serum albumin-based nanocarriers with endosomal escaping and NIR light-controlled release to overcome multidrug resistance of breast cancer cells

The development of nanocarrier-based drug delivery systems is essential to fight against multidrug-resistant (MDR) breast cancer. Herein, we firstly conjugated bovine serum albumin (BSA) with triphenylphosphonium (TPP), and then encapsulated model anticancer drug (doxorubicin, DOX) and photothermal reagent (IR820) via one-pot synthesis of glutathione reduction, to obtain BSA-TPP@(IR820/DOX) nanocomposites. Compared to BSA@(IR820/DOX) with no TPP modifications as a control, BSA-TPP@(IR820/DOX) nanocomposites could be internalized by MDR breast cancer cells with higher efficiency, and rapidly escape from the intracellular endo-/lysosomes into cytoplasms. Moreover, they also had a good behavior of dual pH/NIR light-controlled release of DOX molecules. On this basis, BSA-TPP@(IR820/DOX) nanocomposites exhibited an enhanced inhibitive activity against the proliferation of MDR breast cancer cells via combined chemo-photothermal therapy. Considering the excellent biosafty of BSA, we suggested that this delivery nanosystem developed here has a great promise to overcome MDR of breast cancer in future clinic.

Self-assembled micelles of the natural medicine ginsenosides for cancer metastasis therapy

The nanocarrier-based drug delivery systems have become an alternative strategy for cancer treatment. Whereas, increasing studies find that the utilization of drug carriers may result in poor biocompatibility, lower drug loading capacity and unpredictable side reactions. Therefore, we herein reported self-assembled micelles based on herbal product ginsenosides, which are the main active ingredients of Panax ginseng C.A. The ginsenosides-based micelle system exerts excellent biosafety, better stability, high drug capacity, and lower cytotoxicity compared to free ginsenosides. Meanwhile, ginsenosides micelles exhibits superior inhibitory effects on cancer cell adhesion activity, especially the expression of intercellular adhesion molecule-1, which is the critical factor of cancer metastasis. Importantly, ginsenosides micelles results in remarkably therapeutic efficacy on lung metastasis of liver cancer. All these results highlight the potential utilization of ginsenosides micelles in the clinic. Meanwhile, the carrier-free nano-drugs self-delivery system of ginsenosides showed great promise to become an emerging approach for cancer metastasis therapy.

Biomaterial-based strategy for bone tumor therapy and bone defect regeneration: An innovative application option

Bone tumors are deadly and incurable diseases that invade large areas of bone, resulting in bone defects. Traditional therapies combining surgery, chemotherapy, and radiation have reached their limit of efficacy, motivating efforts to develop new therapeutic methods. Fortunately, the development of biomaterials provides innovative options for bone tumor treatment. Suitable biomaterials are capable of simultaneously providing tumor therapy and promoting bone regeneration. This review summarizes recent progress in the effort to achieve new strategies for bone tumor treatment using biomaterials, focusing on the innovative scaffold design. It also discusses the development of nanocarrier-based drug delivery systems and hyperthermia therapy for bone tumor treatment. In the future, biomaterial-based strategies are likely to become the most effective and reliable options for treating bone tumors, and they have the potential to greatly improve the prognosis and quality of life for patients.

Cancer therapeutics strategy using nano-carrier mediated natural drugs

Nucleolin is a multifactorial protein, having a significant role in chromatin remodelling, mRNA stability, ribosome biogenesis, stemness, angiogenesis, etc., thus, it is potential therapeutic target in cancer. The purpose of this paper is to study porous silicon (pSi) nanocarrier-based natural drug delivery system targeting dysregulated nucleolin expression for cancer therapeutics. Quercetin was loaded in pre-synthesized and characterized pSi nanoparticles, and release kinetics was studied. The study compared the inhibitory concentration (IC50) of quercetin, synthetic drug doxorubicin, and quercetin-loaded pSi nanoparticles. Further, mRNA expression of a target gene, nucleolin, was tested with a quercetin treated breast cancer cell line (MCF-7). Quercetin-loaded pSi nanoparticles followed first-order release kinetics. IC50 was determined at concentrations of 312 nM, 160 µM, and 50 µM against doxorubicin, quercetin, and quercetin-loaded pSi nanoparticles, respectively. The results further indicated 16-fold downregulation of nucleolin mRNA expression after 48h of quercetin treatment of exponentially growing MCF-7 cells. Whether pSi nanoparticle loaded quercetin can significantly downregulate nucleolin protein expression and its impact on apoptosis, cell proliferation, and angiogenic pathways need further investigation. The practical application of the proposed nanocarrier-based drug delivery system potentially lays out a path for developing targeted therapy against nucleolin-dysregulated cancer using natural products to minimize the side effects of conventional chemotherapeutic drugs. Inhibition of nucleolin and nucleolin regulated pathways using natural compounds and its targeted delivery with nanocarrier is not yet done.

Trends in advanced oral drug delivery system for curcumin: A systematic review.

Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed positive impacts of NDS for enhancement of oral absorption of curcumin.