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1.
Mol Neurobiol ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829514

ABSTRACT

Stroke, a severe medical condition arising from abnormalities in the coagulation-fibrinolysis cycle and metabolic processes, results in brain cell impairment and injury due to blood flow obstruction within the brain. Prompt and efficient therapeutic approaches are imperative to control and preserve brain functions. Conventional stroke medications, including fibrinolytic agents, play a crucial role in facilitating reperfusion to the ischemic brain. However, their clinical efficacy is hampered by short plasma half-lives, limited brain tissue distribution attributed to the blood-brain barrier (BBB), and lack of targeted drug delivery to the ischemic region. To address these challenges, diverse nanomedicine strategies, such as vesicular systems, polymeric nanoparticles, dendrimers, exosomes, inorganic nanoparticles, and biomimetic nanoparticles, have emerged. These platforms enhance drug pharmacokinetics by facilitating targeted drug accumulation at the ischemic site. By leveraging nanocarriers, engineered drug delivery systems hold the potential to overcome challenges associated with conventional stroke medications. This comprehensive review explores the pathophysiological mechanism underlying stroke and BBB disruption in stroke. Additionally, this review investigates the utilization of nanocarriers for current therapeutic and diagnostic interventions in stroke management. By addressing these aspects, the review aims to provide insight into potential strategies for improving stroke treatment and diagnosis through a nanomedicine approach.

2.
Life Sci ; 350: 122747, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38797364

ABSTRACT

AIMS: To present the recent update on the isolation, engineering techniques for extracellular vesicles, limitations associated with different isolation techniques, different biomedical applications, and challenges of engineered extracellular vesicles for the benefit of researchers from academic, industry, etc. MATERIALS AND METHODS: Peer-reviewed articles from most recognized journals were collected, and presented information was analyzed to discuss collection, chemical, electroporation, cellular, and membrane surface engineering to design extracellular vesicles for various therapeutic applications. In addition, we present the applications and limitations of techniques for the collection of extracellular vesicles. KEY FINDINGS: There is a need for isolation techniques with the gold standard. However, advanced extracellular vesicle isolation techniques showed improved recovery, and purity of extracellular vesicles. Tumor therapy is a major part of the therapy section that illustrates the role of engineered extracellular vesicles in synergetic therapy such as phototherapy, theragnostic, and delivery of genetic materials. In addition, extracellular vesicles have shown their potential in the treatment of retinal disorders, neurodegenerative disease, tuberculosis, osteoporosis, inflammatory bowel disease, vaccine production, and wound healing. SIGNIFICANCE: Engineered extracellular vesicles can deliver cargo to the specific cells, elicit an immune response and could be used for the development of the vaccines in the future. However, the progress is at the initial stage. Overall, this review will provide a comprehensive understanding and could serve as a reference for researchers in the clinical translation of engineered extracellular vesicles in different biomedical fields.


Subject(s)
Extracellular Vesicles , Extracellular Vesicles/transplantation , Extracellular Vesicles/metabolism , Humans , Animals , Drug Delivery Systems/methods
3.
Ageing Res Rev ; 98: 102318, 2024 07.
Article in English | MEDLINE | ID: mdl-38705362

ABSTRACT

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive loss of memory. Presently, AD is challenging to treat with current drug therapy as their delivery to the brain is restricted by the presence of the blood-brain barrier. Nanomedicines, due to their size, high surface volume ratio, and ease of tailoring drug release characteristics, showed their potential to treat AD. The nanotechnology-based formulations for brain targeting are expected to enter the market in the near future. So, regulatory frameworks are required to ensure the quality, safety, and effectiveness of the nanomedicines to treat AD. In this review, we discuss different strategies, in-vitro blood-brain permeation models, in-vivo permeation assessment, and regulatory aspects for the development of nanomedicine to treat AD.


Subject(s)
Alzheimer Disease , Nanomedicine , Alzheimer Disease/drug therapy , Humans , Nanomedicine/methods , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Drug Delivery Systems/methods
4.
Mol Neurobiol ; 61(3): 1383-1403, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37707740

ABSTRACT

Stroke accounts for one of the top leading reasons for neurological mortality and morbidity around the globe. Both ischemic and hemorrhagic strokes lead to local hypoxia and are brought about by the occlusion or rupturing of the blood vessels. The events taking place after the onset of a stroke include membrane ion pump failure, calcium and glutamate-mediated excitotoxicity, increased ROS production causing DNA damage, mitochondrial dysfunction, oxidative stress, development of brain edema, and microvascular dysfunction. To date, tissue plasminogen activator (tPA) therapy and mechanical removal of blood clots are the only clinically available stroke therapies, approved by Food and Drug Administration (FDA). But because of the narrow therapeutic window of around 4.5 h for tPA therapy and complications like systemic bleeding and anaphylaxis, more clinical trials are ongoing in the same field. Therefore, using nanocarriers with diverse physicochemical properties is a promising strategy in treating and diagnosing stroke as they can efficiently bypass the tight blood-brain barrier (BBB) through mechanisms like receptor-mediated transcytosis and help achieve controlled and targeted drug delivery. In this review, we will mainly focus on the pathophysiology of stroke, BBB alterations following stroke, strategies to target BBB for stroke therapies, different types of nanocarriers currently being used for therapeutic intervention of stroke, and biomarkers as well as imaging techniques used for the detection and diagnosis of stroke.


Subject(s)
Brain Ischemia , Stroke , Humans , Tissue Plasminogen Activator , Brain Ischemia/drug therapy , Stroke/diagnosis , Stroke/therapy , Stroke/complications , Hemorrhage/complications , Blood-Brain Barrier
5.
Drug Discov Today ; 28(12): 103822, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37949429

ABSTRACT

Despite extensive research, a complete cure remains lacking for most types of cancer. Nanotechnology-based carriers, such as liposomes, nanoparticles (NPs), dendrimers, nanoemulsions, and other nanocarriers, can target cancer cells, but their in vivo fate is unpredictable. Bioinspired quantum dots (BQDs) offer enhanced aqueous solubility, exceptionally low toxicity, biocompatibility, easy biofunctionalization, and selective cancer targeting. Due to their photoluminescence, high longitudinal relaxation value, photothermal effect upon laser irradiation, generation of singlet oxygen, and production of H2S for gas therapy, BQDs are excellent cancer theranostic agents. In this review, we highlight the theranostic application of, and existing challenges relating to BQDs.


Subject(s)
Nanoparticles , Neoplasms , Quantum Dots , Humans , Precision Medicine , Theranostic Nanomedicine , Nanoparticles/therapeutic use , Neoplasms/diagnosis , Neoplasms/drug therapy
6.
Drug Dev Ind Pharm ; 49(12): 734-747, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37982183

ABSTRACT

OBJECT: We report the preparation, characterization, and in-vitro therapeutic evaluation of Metformin-Loaded, Transferrin-Poloxamer-Functionalized Chitosan Nanoparticles (TPMC-NPs) for their repurposing in Alzheimer's disease (AD). SIGNIFICANCE: Usefulness of this work to establish the repurposing of metformin for the treatment of AD. METHODS: The TPMC-NPs were prepared by ionic gelation method using sodium tripolyphosphate. The modification and functionalization were confirmed by FTIR and 1H-NMR spectroscopy. The physicochemical characterization was performed using DLS, FTIR,1H-NMR, CD spectroscopy, SEM, DSC, PXRD, HR-TEM, and hot-stage microscopy. RESULTS: The size, PDI, percent entrapment efficiency, and percent drug loading of TPMC-NPs were found to be 287.4 ± 9.5, 0.273 ± 0.067, 81.15 ± 7.17%, 11.75%±8.21%, respectively. Electron microscope analysis revealed smooth and spherical morphology. The transferrin conjugation efficiency was found to be 46% by the BCA method. CD spectroscopy confirmed no significant loss of the secondary structure of transferrin after conjugation. PXRD data indicated the amorphous nature of the TPMC-NPs. Hot-stage microscopy and DSC confirmed the thermal stability of TPMC-NPs. The in-vitro drug release showed a sustained release at pH 7.4. The DPPH assay displayed 80% antioxidant activity of TPMC-NPs in comparison with metformin and blank NPs. The in-vitro cytotoxicity assay revealed 69.60% viable SH- SY5Y cells at 100 µg/mL of TPMC NPs. The ex-vivo nasal ciliotoxicity and mucoadhesion studies showed no significant toxicity, and 98.16% adhesion, respectively. The nasal permeability study showed the release of metformin within 30 min from TPMC-NPs. CONCLUSION: The obtained results suggested the usefulness of TPMC-NPs in the treatment of AD via the intranasal route.


Subject(s)
Alzheimer Disease , Chitosan , Metformin , Nanoparticles , Humans , Drug Carriers/chemistry , Chitosan/chemistry , Poloxamer/chemistry , Transferrin , Metformin/pharmacology , Alzheimer Disease/drug therapy , Nanoparticles/chemistry , Particle Size
7.
Eur J Pharmacol ; 961: 176117, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37907134

ABSTRACT

The risk of neurodegeneration was found to be increased among people with type 2 diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are considered neurodegenerative diseases and can be characterized by progressive loss of neurons. The deficiency of insulin, impaired signaling, and its resistance lead to alteration in the neuronal functioning of the brain. Insulin degrading enzyme (IDE) plays a significant role in the amyloid ß metabolism, aggregation, and deposition of misfolded proteins in the brain's hippocampal and cortical neuronal regions. The insulin signaling via IP3 activation upregulates the IDE and could be a promising approach to regulate neurodegeneration. The repurposing of existing antidiabetic drugs such as Metformin, DPP-4 inhibitors, thiazolidinediones, glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy to treat neurodegeneration via modulating insulin signaling, insulin resistance, IDE activity, oxidative stress, mitochondrial dysfunction, serum lipid profile and neuroinflammation in the brain. Antidiabetic medications reduce the risk of neuroinflammation, oxidative stress, and Aß deposition by enhancing their clearance rate. The downregulation of IDE alters the degradation of Aß monomers in the Tg2576 APP mice. Also, the treatment with metformin activated the AMPK pathway and suppressed mTOR and BACE-1 protein expression in the APP/PS1-induced mice model. Thus, the primary intention of this review is to explore the link between T2DM and neurodegenerative disorders, and the possible role of various antidiabetic drugs in the management of neurodegenerative disorders.


Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Metformin , Humans , Mice , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Amyloid beta-Peptides/metabolism , Diabetes Mellitus, Type 2/drug therapy , Drug Repositioning , Neuroinflammatory Diseases , Alzheimer Disease/drug therapy , Insulin/metabolism , Metformin/pharmacology
8.
Curr Pharm Des ; 29(10): 732-747, 2023.
Article in English | MEDLINE | ID: mdl-36999427

ABSTRACT

Recently, breast cancer has reached the highest incident rate amongst all the reported cancers, and one of its variants, known as triple-negative breast cancer (TNBC), is deadlier compared to the other types of breast cancer due to a lack of feasible diagnostic techniques. Advancements in nanotechnology have paved the way to formulate several nanocarriers with the ability to deliver anticancer drugs effectively and selectively to cancer cells with minimum side effects to non-cancerous cells. Nanotheranostics is a novel approach that can be used in the diagnosis of disease along with therapeutic effects. Currently, various imaging agents, such as organic dyes, radioactive agents, upconversion nanoparticles, various contrasting agents, quantum dots, etc., are being explored for the imaging of internal organs or to examine drug distribution. Furthermore, ligand-targeted nanocarriers, which have the potential to target cancer sites, are being used as advanced agents for cancer theranostic applications, including the identification of various metastatic sites of the cancerous tumor. This review article discusses the need for theranostic application in breast cancer with various imaging techniques, the latest nanotheranostic carriers in breast cancer, and related safety and toxicity issues, as well as highlights the importance of nanotheranostics in breast cancer, which could be helpful in deciphering questions related to nanotheranostic systems.


Subject(s)
Antineoplastic Agents , Nanoparticles , Triple Negative Breast Neoplasms , Humans , Theranostic Nanomedicine/methods , Antineoplastic Agents/therapeutic use , Nanoparticles/therapeutic use , Drug Carriers , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/drug therapy
9.
Drug Deliv Transl Res ; 13(6): 1730-1744, 2023 06.
Article in English | MEDLINE | ID: mdl-36641487

ABSTRACT

PlK1 has a significant role in the development of breast cancer. Thus, silencing of PlK1 gene may arrest the growth of breast cancer. However, the in vivo stability of PlK1 siRNA after injection remains a challenge to target the specific site. The delivery of siPlK1 RNA via viral vector and amine group-terminated dendrimer is associated with immune reaction and cellular cytotoxicity. Thus, in the present study, hyaluronic acid-functionalized and -thiolated polycaprolactone nanoparticles (SH-HPP NPs) were developed for enhancing the targeting capabilities of siRNA towards human breast cancer cells. NPs displayed size in the range of 180-217 nm, and with sustain and pH-dependent release of siRNA up to 120 h. The in vitro treatments with siRNA-containing NPs showed the high number of necrotic cells and the cell cycle arrest at the G2/M phase. The gene expression analysis depicts the decrease of endogenous PLK1 siRNA expression on MCF-7 cells upon PLK1 NPs treatment. In vitro cytotoxicity experiments demonstrated effective anticancer properties against MCF-7. Finally, in vivo results showed that substantial tumor inhibition was achieved with PLK1 siRNA-containing SH-HPP NPs in comparison of the control group. Hence, HPP NPs have enormous potential for the selective delivery of siRNA, i.e., breast cancer cells.


Subject(s)
Breast Neoplasms , Nanoparticles , Female , Humans , Cell Line, Tumor , Hyaluronic Acid , RNA, Small Interfering , Polo-Like Kinase 1
10.
CNS Neurol Disord Drug Targets ; 22(4): 477-499, 2023.
Article in English | MEDLINE | ID: mdl-35450536

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is characterized by the presence of aggregated amyloid fibers, neurodegeneration, and loss of memory. Although "Food and Drug Administration" (FDA) approved drugs are available to treat AD, drugs that target AD have limited access to the brain and cause peripheral side effects. These peripheral side effects are the results of exposure of peripheral organs to the drugs. The blood-brain barrier (BBB) is a very sophisticated biological barrier that allows the selective permeation of various molecules or substances. This selective permeation by the BBB is beneficial and protects the brain from unwanted and harmful substances. However, this kind of selective permeation hinders the access of therapeutic molecules to the brain. Thus, a peculiar drug delivery system (nanocarriers) is required. OBJECTIVE: Due to selective permeation of the "blood-brain barrier," nanoparticulate carriers may provide special services to deliver the drug molecules across the BBB. This review article is an attempt to present the role of different nanocarriers in the diagnosis and treatment of Alzheimer's disease. METHODS: Peer-reviewed and appropriate published articles were collected for the relevant information. RESULT: Nanoparticles not only traverse the blood-brain barrier but may also play roles in the detection of amyloid ß, diagnosis, and drug delivery. CONCLUSION: Based on published literature, it could be concluded that nano-particulate carriers may traverse the blood-brain barrier via the transcellular pathway, receptor-mediated endocytosis, transcytosis, and may enhance the bioavailability of drugs to the brain. Hence, peripheral side effects could be avoided.


Subject(s)
Alzheimer Disease , Nanoparticles , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Brain/metabolism , Blood-Brain Barrier/metabolism , Drug Delivery Systems/methods , Nanoparticles/therapeutic use
11.
Mol Neurobiol ; 59(8): 4806-4824, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35618981

ABSTRACT

The aim of the present review article is to summarize the role of nanodiamonds in various neurological diseases. We have taken related literature of making this review article from ScienceDirect, springer, Research gate, PubMed, Sci-finder, etc. The current approaches for treating neurological conditions such as glioblastoma includes chemotherapy or combination anti-retro viral therapy for HIV (human immunodeficiency virus) or use of anti-Alzheimer drugs during cognitive impairment. These approaches can provide only symptomatic relief as they do not target the cause of the disease due to their inability to penetrate the blood brain barrier. On long-term use, they may cause CNS toxicity due to accumulation in the brain. So nanodiamonds could prove as a promising approach in the brain targeting of the bioactive and to treat many neurological disorders such as Alzheimer's disease, Parkinson's disease, brain tumor (glioblastoma), HIV, amyotrophic multiple sclerosis, Huntington disease, stroke (cerebrovascular attack), batten disease, schizophrenia, epilepsy, and bacterial infections (encephalitis, sepsis, and meningitis) due to their ability to penetrate the blood-brain barrier and owing to their excellent surface properties, i.e., nano size and high surface area, ease of functionalization, multiple drug binding, and biocompatibility; they can be useful for brain targeted drug delivery with minimal side effects.


Subject(s)
Glioblastoma , Nanodiamonds , Nervous System Diseases , Blood-Brain Barrier/metabolism , Brain/metabolism , Drug Delivery Systems , Glioblastoma/metabolism , Humans , Nervous System Diseases/drug therapy , Nervous System Diseases/metabolism
12.
Expert Opin Drug Deliv ; 19(1): 87-102, 2022 01.
Article in English | MEDLINE | ID: mdl-35040728

ABSTRACT

INTRODUCTION: The irreversible destruction of neurons, progressive loss of memory and cognitive behavior, high cost of therapy, and impact on society, desire a better, effective, and affordable treatment of AD. The nose-to-brain delivery approach holds great potential to access the brain without any hindrance of BBB and results in higher bioavailability and thus better therapeutic efficacy of anti-AD drugs. AREAS COVERED: The present review article highlights the current facts and worldwide statistics of AD and its detailed etiology. This is followed by barriers to brain delivery, nose-to-brain delivery, their limitations, and amalgamation with various novel carrier systems. We have emphasized recent advancements in nose-to-brain delivery using mucoadhesive, stimuli-responsive carriers, polymeric nanoparticles, lipid nanoparticles, and protein/peptide delivery for treatment of AD. EXPERT OPINION: The available therapies are symptomatic and mitigate the symptoms of AD at the initial stages. In lieu of this, nose-to-brain delivery has the ability to overcome these limitations and increase drug bioavailability in the brain. Various novel strategies including stimuli-responsive systems, nanoparticles, etc. enhance the nasal permeation, protect the drug, and enhance its therapeutic potency. However, successful preclinical data do not assure the clinical success of the therapy, and hence exhaustive clinical investigations are needed to make the therapy available for patients.


Subject(s)
Alzheimer Disease , Nanoparticles , Alzheimer Disease/drug therapy , Blood-Brain Barrier , Brain , Drug Delivery Systems/methods , Humans , Liposomes
13.
Curr Pharm Biotechnol ; 23(12): 1460-1482, 2022.
Article in English | MEDLINE | ID: mdl-34579630

ABSTRACT

Burn wounds are complex and intricate injuries that have become a common cause of trauma leading to significant mortality and morbidity every year. Dressings are applied to burn wounds with the aim of promoting wound healing, preventing burn infection and restoring skin function. The dressing protects the injury and contributes to recovery of dermal and epidermal tissues. Polymer-based nanotherapeutics are increasingly being exploited as burn wound dressings. Natural polymers such as cellulose, chitin, alginate, collagen, gelatin and synthetic polymers like poly (lactic-co-glycolic acid), polycaprolactone, polyethylene glycol, and polyvinyl alcohol are being obtained as nanofibers by nanotechnological approaches like electrospinning and have shown wound healing and re-epithelialization properties. Their biocompatibility, biodegradability, sound mechanical properties and unique structures provide optimal microenvironment for cell proliferation, differentiation, and migration contributing to burn wound healing. The polymeric nanofibers mimic collagen fibers present in extracellular matrix and their high porosity and surface area to volume ratio enable increased interaction and sustained release of therapeutics at the site of thermal injury. This review is an attempt to compile all recent advances in the use of polymer-based nanotherapeutics for burn wounds. The various natural and synthetic polymers used have been discussed comprehensively and approaches being employed have been reported. With immense research effort that is currently being invested in this field and development of proper characterization and regulatory framework, future progress in burn treatment is expected to occur. Moreover, appropriate preclinical and clinical research will provide evidence for the great potential that polymer-based nanotherapeutics hold in the management of burn wounds.


Subject(s)
Burns , Polymers , Bandages , Burns/drug therapy , Collagen/metabolism , Humans , Nanomedicine , Polymers/therapeutic use , Wound Healing
14.
J Microencapsul ; 38(7-8): 572-593, 2021.
Article in English | MEDLINE | ID: mdl-34591731

ABSTRACT

AIM: The inability of drug molecules to cross the 'Blood-Brain Barrier' restrict the effective treatment of Alzheimer's disease. Lipid nanocarriers have proven to be a novel paradigm in brain targeting of bioactive by facilitating suitable therapeutic concentrations to be attained in the brain. METHODS: The relevant information regarding the title of this review article was collected from the peer-reviewed published articles. Also, the physicochemical properties, and their in vitro and in vivo evaluations were presented in this review article. RESULTS: Administration of lipid-based nano-carriers have abilities to target the brain, improve the pharmacokinetic and pharmacodynamics properties of drugs, and mitigate the side effects of encapsulated therapeutic active agents. CONCLUSION: Unlike oral and other routes, the Intranasal route promises high bioavailability, low first-pass effect, better pharmacokinetic properties, bypass of the systemic circulation, fewer incidences of unwanted side effects, and direct delivery of anti-AD drugs to the brain via circumventing 'Blood-Brain Barrier'.


Subject(s)
Alzheimer Disease , Nanoparticles , Administration, Intranasal , Alzheimer Disease/drug therapy , Blood-Brain Barrier , Brain , Drug Delivery Systems , Humans , Lipids
15.
Crit Rev Ther Drug Carrier Syst ; 38(4): 39-78, 2021.
Article in English | MEDLINE | ID: mdl-34369739

ABSTRACT

Nanodiamonds (ND) belong to the nano-carbon family, which involves several synthesis, post-synthesis methods, and other modifications for ND preparation. NDs have played vital role both inside and outside of medicine in recent years. The study of NDs has stated in early 1960s, NDs are smaller particles with a size of about 4-5 nm with confined size distribution, large-scale synthesis at lower costs relying on the carbon explosives ignition, apparent surface functional design along with bio-conjugation and extreme biocompatibility. It has been predicted that the ND's magnetic characteristics will contribute to the up-growth of various therapeutic promoters for delivery vehicles, diagnostic probes, gene therapy, tissue scaffolds, anti-bacterial and anti-viral treatments, and devices like nano-robots. Furthermore, the wide applications of biotechnology have displayed the potential usage of NDs in certain bioanalytical needs like fluorescent bio labeling through fluorescent and protein purification of proteins. In this current review, the determination of ND's design, property, classes, constancy, organization, surface modification, biocompatibility, and its applications in the biomedical field have penned. The usage of ND as anti-neoplastic agents and in other health related formulations have displayed exceptional results for future growth. Additionally, NDs provide other functionalities such as production of biodegradable surgical devices of bone, the assassination of drug resistant microbes and viruses, tissue engineering scaffolds, and aids in the delivery of genetic matter into the nucleus of cells.


Subject(s)
Antineoplastic Agents , Nanodiamonds , Drug Carriers , Drug Delivery Systems , Tissue Engineering
16.
Drug Discov Today ; 26(12): 2881-2888, 2021 12.
Article in English | MEDLINE | ID: mdl-34332094

ABSTRACT

Alzheimer's disease (AD) is an irreversible dementia state with characteristic clinical manifestations, including declining cognitive skills and loss of memory, which particularly affects the older population. Despite significant efforts in the field of nano-based drug delivery, there have been few successes achieved in the design of a rational drug therapy. Nanoemulsions (NEs) have potential for the delivery of AD therapeutics owing to their capability for brain drug delivery. Still, there is a long way to go before such therapeutics become a reality in the clinic. In this review, we highlight the preclinical assessment of NEs for AD and discuss the regulatory constraints to their clinical acceptance.


Subject(s)
Alzheimer Disease/drug therapy , Drug Delivery Systems , Nanoparticles , Aged , Alzheimer Disease/physiopathology , Animals , Brain/metabolism , Brain/physiopathology , Drug Evaluation, Preclinical/methods , Emulsions , Humans , Tissue Distribution
17.
Nanomaterials (Basel) ; 11(2)2021 Feb 07.
Article in English | MEDLINE | ID: mdl-33562310

ABSTRACT

Three-dimensional (3D) printing is gaining numerous advances in manufacturing approaches both at macro- and nanoscales. Three-dimensional printing is being explored for various biomedical applications and fabrication of nanomedicines using additive manufacturing techniques, and shows promising potential in fulfilling the need for patient-centric personalized treatment. Initial reports attributed this to availability of novel natural biomaterials and precisely engineered polymeric materials, which could be fabricated into exclusive 3D printed nanomaterials for various biomedical applications as nanomedicines. Nanomedicine is defined as the application of nanotechnology in designing nanomaterials for different medicinal applications, including diagnosis, treatment, monitoring, prevention, and control of diseases. Nanomedicine is also showing great impact in the design and development of precision medicine. In contrast to the "one-size-fits-all" criterion of the conventional medicine system, personalized or precision medicines consider the differences in various traits, including pharmacokinetics and genetics of different patients, which have shown improved results over conventional treatment. In the last few years, much literature has been published on the application of 3D printing for the fabrication of nanomedicine. This article deals with progress made in the development and design of tailor-made nanomedicine using 3D printing technology.

18.
Int J Pharm ; 557: 238-253, 2019 Feb 25.
Article in English | MEDLINE | ID: mdl-30594688

ABSTRACT

The intention of present research work is to formulate usnic acid (UA) loaded heparin modified gellan gum (HAG) nanoparticles (NPs). HAG copolymer based conjugation was synthesized and characterized by 1H NMR and FT-IR spectroscopy. Plain and UA loaded HAG NPs were prepared via nanoprecipitation technique. NPs were typified and further characterized for particle size, polydispersity index, entrapment efficiency, zeta potential, atomic force microscopy, differential scanning calorimetry, X-ray diffraction analysis, and in-vitro release. In-vitro tube formation assay, tumorsphere assay, autophagy assay, DNA cleavage assay, internalization by confocal and FACS based internalization analysis, caspase assay and cell cycle assay were performed for biological activity. Obtained experimental results explored that HAG NPs displayed a sustained release of UA (95.67% in 48 h) compared to gellan gum NPs (96.12% in 8 h). In cytotoxicity studies, UA loaded HAG NPs exhibited an enormous cytotoxic potential against A549 cancer cells. In the in vivo bio-distribution study, using albino rat model the free UA concentration was found 7.09 ±â€¯0.9%, 2.7 ±â€¯1.5%, 7.5 ±â€¯2.1, 9.2 ±â€¯2%, and 6.25 ±â€¯1.3% post two hours of intravenous administration, however, in the case of UA loaded HAG NPs the obtained level was 4.1 ±â€¯1.10, 7.7 ±â€¯1.30%, 2.21 ±â€¯0.29%, 1.85 ±â€¯0.25%, 2.2 ±â€¯0.78%, 2.9 ±â€¯1.21% respectively, in heart, lung, liver, spleen, intestine and kidney. The overall anticancer study and result of internalization deciphered the higher anticancer potential of UA loaded HAG NPs.


Subject(s)
Adipates/administration & dosage , Antineoplastic Agents/administration & dosage , Benzofurans/administration & dosage , Drug Carriers/administration & dosage , Heparin/administration & dosage , Nanoparticles/administration & dosage , Polysaccharides, Bacterial/administration & dosage , A549 Cells , Adipates/chemistry , Adipates/pharmacokinetics , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Apoptosis/drug effects , Benzofurans/chemistry , Benzofurans/pharmacokinetics , Cell Cycle/drug effects , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Liberation , Erythrocytes/drug effects , Hematologic Tests , Hemolysis/drug effects , Heparin/chemistry , Heparin/pharmacokinetics , Humans , Male , Nanoparticles/chemistry , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/pharmacokinetics , Rats
19.
ACS Biomater Sci Eng ; 4(8): 2860-2869, 2018 Aug 13.
Article in English | MEDLINE | ID: mdl-33435009

ABSTRACT

The present study was aimed at delivering a low bioavailability drug, rivastigmine hydrogen tartrate (RTG), to the brain through its encapsulation in mesoporous silica nanoparticles (MSNs) and targeted to amyloid inhibition in the brain. MSNs were characterized for size, zeta potential, and drug entrapment using SEM, TEM, HR-TEM, FT-IR, and PXRD. Drug-loaded MSNs were assessed for in vitro release kinetics and ex vivo followed by animal studies. The average size of the prepared blank (MCM-41B) and drug-loaded MSNs (MCM-41L) was 114 ± 2.0 and 145 ± 0.4 nm with the zeta potential of approximately -43.5 ± 1.1 and -37.6 ± 1.4 mV, respectively. MCM-41L exhibited an average entrapment efficiency of 88%. In vitro release studies exhibited early surge followed by a sluggish persistent or constant release (biphasic pattern). Hemolytic studies proved that the developed MCM-41L NPs are less hemolytic compared to RTG. A reduced ThT fluorescence was observed with MCM-41L compared to MCM-41B and RTG in the amyloid inhibition studies. A significant (p < 0.05) inhibition of AChE (acetycholinesterase) was observed for MCM-41L (80 ± 4.98%), RTG (62 ± 3.25%), and MCM-41B (54 ± 4.25%). In vivo pharmacokinetics in Wistar rats revealed that the AUC and mean residence time (MRT) for MCM-41L was sustained and significantly higher (p < 0.05) (780 ± 3.30 ng/L; 5.49 ± 0.25 h) compared to RTG solution (430 ± 3.50 ng/L; 0.768 ± 0.17 h). Similarly, the half-life was found to be significantly higher in case of MCM-41L. The promising result was brain delivery of RTG in Wistar rats which was enhanced almost 127 folds in vivo, using MCM-41L nanoparticles. MCM-41L nanoparticles effectively enhanced the bioavailability of RTG. Conclusively, these can be used for the administration of RTG and other related low bioavailability drugs for improved brain delivery.

20.
Artif Cells Nanomed Biotechnol ; 46(3): 452-464, 2018 May.
Article in English | MEDLINE | ID: mdl-28685588

ABSTRACT

Mucosal administration of vaccine is most prevalent way to induce desired immunity against various types of antigen and microbial in central and in addition, the peripheral blood in most external mucosal surface. Mucosal delivery of vaccine provides both humoral and cellular responses against mucosal infection. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganism, are one of the main region where infections are built up, also, thus have frontline status in immunity, making mucosa perfect site for vaccines application. The nasal route is favoured over parenteral route due to ease of administration, protection of antigen from degradation and induces sIgA which is not produced by systemic immunity. Natural and synthetic polymers are utilized to get nanoparticles carrier systems for development of nasal mucosal antibodies. The present review summarized the recent development in the field of vaccine delivery by means of mucoadhesive polymeric carriers. This review also describes the recent patent conceded for mucosal immunization utilizing these polymeric carriers.


Subject(s)
Biodegradable Plastics/therapeutic use , Drug Carriers/therapeutic use , Immunity, Mucosal/drug effects , Immunization/methods , Nanoparticles/therapeutic use , Nasal Mucosa/immunology , Animals , Humans , Immunoglobulin A, Secretory/immunology
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