scholarly journals Do Lipid-Based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5346
Author(s):  
Jian Sheng Loh ◽  
Li Kar Stella Tan ◽  
Wai Leng Lee ◽  
Long Chiau Ming ◽  
Chee Wun How ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticancer Agents ◽  
In Vitro Cytotoxicity ◽  
Clinical Translation ◽  
Toxicity Profile ◽  
Toxicity Data ◽  
In Vivo Efficacy ◽  
Broad Application

Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.

Polymeric/Inorganic Multifunctional Nanoparticles for Simultaneous Drug Delivery and Visualization

2010 ◽  
Vol 1257 ◽  
Author(s):  
Andrea Fornara ◽  
Alberto Recalenda ◽  
Jian Qin ◽  
Abhilash Sugunan ◽  
Fei Ye ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluorescence Microscopy ◽  
Contrast Agents ◽  
Gold Nanorods ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Multifunctional Nanoparticles ◽  
Cytotoxicity Studies

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.

scholarly journals Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

2021 ◽  
Vol 12 ◽  
Author(s):  
Josanne S. de Maar ◽  
Charis Rousou ◽  
Benjamin van Elburg ◽  
Hendrik J. Vos ◽  
Guillaume P.R. Lajoinie ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Translation ◽  
Drug Uptake ◽  
Single Element ◽  
Hydrophilic Drug ◽  
Ultrasound System ◽  
Fadu Cells ◽  
Set Up

Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.

Surface functionalized mesoporous silica nanoparticles for intravitreal application of tacrolimus

2020 ◽  
pp. 088532822097760
Author(s):  
Mayara Rodrigues Brandão Paiva ◽  
Gracielle Ferreira Andrade ◽  
Lays Fernanda Nunes Dourado ◽  
Brenda Fernanda Moreira Castro ◽  
Silvia Ligório Fialho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Silica Nanoparticles ◽  
Intravitreal Injection ◽  
Retinal Pigment ◽  
In Vitro Cytotoxicity ◽  
Eye Diseases ◽  
Functionalized Silica ◽  
Functionalized Silica Nanoparticles

Tacrolimus (TAC), a potent immunosuppressive macrolide, has been investigated for ocular diseases due to promising results in the treatment of anterior and posterior segments eye diseases. Mesoporous and functionalized silica nanoparticles show potential as TAC delivery platforms owing to their interesting characteristic as large surface area, uniform pore size distribution, high pore volume, and excellent biocompatibility. The purpose of this study was to incorporate TAC in functionalized silica nanoparticles with 3-aminopropyltriethoxysilane (MSNAPTES) and investigate the safety and biocompatibility of the systems. The MSNAPTES and MSNAPTES TAC nanoparticles were characterized. The in vitro cytotoxicity of MSNAPTES and MSNAPTES load with TAC (MSNAPTES-TAC) in retinal pigment epithelial cells (ARPE-19) was determined, chorioallantoic membrane (CAM) assay model was used to investigate the in vivo biocompatibility, and safety of intravitreal injection was evaluated using clinical examination (assessment of intraocular pressure and indirect fundus ophthalmoscopy), electroretinographic (ERG) and histologic studies in rats’ eyes. The elemental analysis (CHN), thermogravimetric (TGA), photon correlation spectroscopy and Fourier transform infrared (FTIR) analysis confirmed the presence of functionalized agent and TAC in the MSNAPTES nanoparticles. TAC loading was estimated at 7% for the MSNAPTES TAC nanoparticles. MSNAPTES and MSNAPTES TAC did not present in vitro cytotoxicity. The drug delivery systems showed good biocompatibility on CAM. No retinal abnormalities, vitreous hemorrhage, neovascularization, retinal detachment, and optic nerve atrophy were observed during the in vivo study. Follow-up ERGs showed no changes in the function of the retina cells after 15 days of intravitreal injection, and histopathologic observations support these findings. In conclusion, MSNAPTES TAC was successfully synthesized, and physicochemical analyses confirmed the presence of TAC in the nanoparticles. In vitro and in vivo studies indicated that MSNAPTES TAC was safe to intravitreal administration. Taking into account the enormous potential of MSNAPTES to carry TAC, this platform could be a promising strategy for TAC ocular drug delivery in the treatment of eye diseases.

Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression

2016 ◽  
Vol 128 (39) ◽  
pp. 12114-12118 ◽  
Author(s):  
Tommy Tsz-Him Fong ◽  
Chun-Nam Lok ◽  
Clive Yik-Sham Chung ◽  
Yi-Man Eva Fung ◽  
Pui-Keong Chow ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Anticancer Agents ◽  
Growth Suppression ◽  
In Vitro Cytotoxicity ◽  
Carbene Complexes ◽  
Tumor Growth Suppression

scholarly journals Characterization and toxicity of citral incorporated with nanostructured lipid carrier

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e3916 ◽  
Author(s):  
Noraini Nordin ◽  
Swee Keong Yeap ◽  
Nur Rizi Zamberi ◽  
Nadiah Abu ◽  
Nurul Elyani Mohamad ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Anticancer Agents ◽  
Drug Loading ◽  
Cancer Drug ◽  
Nanostructured Lipid Carrier ◽  
Tem Analysis

The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was −12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined viain vitroandin vivoroutes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity.

scholarly journals Degradable 2-Hydroxyethyl Methacrylate/Gelatin/Alginate Hydrogels Infused by Nanocolloidal Graphene Oxide as Promising Drug Delivery and Scaffolding Biomaterials

Gels ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 22
Author(s):  
Marija M. Babić Radić ◽  
Vuk V. Filipović ◽  
Marija Vukomanović ◽  
Jasmina Nikodinović Runić ◽  
Simonida Lj. Tomić
Keyword(s):  
Drug Delivery ◽  
Graphene Oxide ◽  
Entrapment Efficiency ◽  
In Vitro Cytotoxicity ◽  
Hydroxyethyl Methacrylate ◽  
Healthy Human ◽  
Swelling Properties ◽  
Mtt Test

The design and evaluation of novel 2-hydroxyethyl methacrylate/gelatin/alginate/graphene oxide hydrogels as innovative scaffolding biomaterials, which concurrently are the suitable drug delivery carrier, was proposed. The hydrogels were prepared by the adapted porogen leaching method; this is also the first time this method has been used to incorporate nanocolloidal graphene oxide through the hydrogel and simultaneously form porous structures. The effects of a material’s composition on its chemical, morphological, mechanical, and swelling properties, as well as on cell viability and in vitro degradation, were assessed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), measurements of Young’s modulus, gravimeter method and MTT test, respectively. The engineered hydrogels show good swelling capacity, fully hydrophilic surfaces, tunable porosity (from 56 to 76%) and mechanical properties (from 1.69 to 4.78 MPa), curcumin entrapment efficiency above 99% and excellent curcumin release performances. In vitro cytotoxicity on healthy human fibroblast (MRC5 cells) by MTT test reveal that the materials are nontoxic and biocompatible, proposing novel hydrogels for in vivo clinical evaluation to optimize tissue regeneration treatments by coupling the hydrogels with cells and different active agents to create material/biofactor hybrids with new levels of biofunctionality.

scholarly journals Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2632
Author(s):  
Mark J. Lynch ◽  
Oliviero L. Gobbo
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Rational Design ◽  
In Vitro Models ◽  
Clinical Translation ◽  
Clinical Testing ◽  
Cns Disorders ◽  
Novel Drug

Nanotheranostics constitute a novel drug delivery system approach to improving systemic, brain-targeted delivery of diagnostic imaging agents and pharmacological moieties in one rational carrier platform. While there have been notable successes in this field, currently, the clinical translation of such delivery systems for the treatment of neurological disorders has been limited by the inadequacy of correlating in vitro and in vivo data on blood–brain barrier (BBB) permeation and biocompatibility of nanomaterials. This review aims to identify the most contemporary non-invasive approaches for BBB crossing using nanotheranostics as a novel drug delivery strategy and current non-animal-based models for assessing the safety and efficiency of such formulations. This review will also address current and future directions of select in vitro models for reducing the cumbersome and laborious mandate for testing exclusively in animals. It is hoped these non-animal-based modelling approaches will facilitate researchers in optimising promising multifunctional nanocarriers with a view to accelerating clinical testing and authorisation applications. By rational design and appropriate selection of characterised and validated models, ranging from monolayer cell cultures to organ-on-chip microfluidics, promising nanotheranostic particles with modular and rational design can be screened in high-throughput models with robust predictive power. Thus, this article serves to highlight abbreviated research and development possibilities with clinical translational relevance for developing novel nanomaterial-based neuropharmaceuticals for therapy in CNS disorders. By generating predictive data for prospective nanomedicines using validated in vitro models for supporting clinical applications in lieu of requiring extensive use of in vivo animal models that have notable limitations, it is hoped that there will be a burgeoning in the nanotherapy of CNS disorders by virtue of accelerated lead identification through screening, optimisation through rational design for brain-targeted delivery across the BBB and clinical testing and approval using fewer animals. Additionally, by using models with tissue of human origin, reproducible therapeutically relevant nanomedicine delivery and individualised therapy can be realised.

Nanosponges Encapsulated Phytochemicals for Targeting Cancer: A Review

2020 ◽  
Vol 21 ◽  
Author(s):  
Shailaja Dombe ◽  
Pramodkumar Shirote
Keyword(s):  
Drug Delivery ◽  
Anticancer Agents ◽  
Biological Properties ◽  
The Body ◽  
Special Focus ◽  
Cancer Therapies ◽  
Nanostructured Particles ◽  
Inorganic Systems

Abstract: Cancer is the most ruinous disease globally. Natural products have impressive characteristics, such as excep-tional chemical versatility, chemical and biological properties of macromolecular specificity and less toxicity which make them good leads in finding novel drugs. The phytochemicals not only help to prevent but also treat chronic cancerous conditions. The present review attempts to put forth some selected anticancer phytochemicals that had reported omics char-acteristic and specifically suppressed cancer with in vitro and in vivo activity. Certain issues pertaining to anticancer phy-tochemicals like delivery to target site in the body and achieving controlled release in order to prevent overdoses havelong been a concern for medical researchers worldwide. The most conventional chemotherapy protocols for the treatment of cancer lead to adverse effects that limit biological efficacy and compromise patient outcomes. In order to defeat incompe-tency of current and upcoming natural anticancer agents and to attain targeted drug delivery with good efficacy and fewer side effects, there is a special focus on novel nanostructured particles and nano approaches consisting of carrier system. Recent studies have led to the discovery of mesoporous and nanoporous drug delivery mechanisms, such as inorganic or organic-based nanosponges. The metal based inorganic systems have exhibited toxicity and non-biodegradable character in vivo. As a result of problems related to inorganic systems, major shift of research from inorganic to organic nanosystems has occurred. About decades ago, researchers have developed organic nanosponges to control the limitation of drug delivery and cancer therapies. This review article discusses the development and application of nanosponges encapsulated phyto-chemicals for cancer therapy.

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