Nanocargos: A Burgeoning Quest in Cancer Management

2020 ◽  
Vol 10 (2) ◽  
pp. 149-163
Author(s):  
Atul Jain ◽  
Teenu Sharma ◽  
Sumant Saini ◽  
Om Prakash Katare ◽  
Vandana. Soni ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Imaging Techniques ◽  
Intestinal Barrier ◽  
Oral Route ◽  
In Vitro Models ◽  
In Vitro Toxicity ◽  
Cancer Management ◽  
Surface Modified

Cancer, a complex series of diseased conditions, contributes to a significant health problem and is a leading cause of mortalities across the world. Lately, with the advent of improved diagnostics and imaging techniques, and newer advanced oral chemotherapeutics; millions of cancer affected people can lengthen their life span. Despite all the challenges associated with an active chemotherapeutic molecule like microenvironment and the intestinal barrier of the gastrointestinal tract (GIT) etc., the oral delivery remains the most acceptable route of drug administration. In this regard, nanotechnology has played a significant role in the counteracting the challenges encountered with newly developed molecules and aiding in improving their bioavailability and targetability to the tumour site, while administering through the oral route. Several literature instances document the usage of nanostructured drug delivery systems such as lipid-based, polymerbased or metallic nanomaterials to improve the efficacy of chemotherapy. Besides, sitespecific targeted surface-modified drug delivery system designed to deliver the active molecule has opened up to the newer avenues of nanotechnology. However, the issue of potential toxicity allied with nanotechnology cannot be compromised and thus, needs specific ethical regulations and guidelines. The various in vitro models have been developed to evaluate the in vitro toxicity profile which can be further correlated with the invivo model. Thus, this review provides a summarized account of the various aspects related to the role of nanotechnology in cancer therapy and various related issues thereof; that must be triumphed over to apprehend its full promise.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

scholarly journals Effect of Chitosan Coating on PLGA Nanoparticles for Oral Delivery of Thymoquinone: In Vitro, Ex Vivo, and Cancer Cell Line Assessments

Coatings ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 6
Author(s):  
Sultan Alshehri ◽  
Syed Sarim Imam ◽  
Md Rizwanullah ◽  
Khalid Umar Fakhri ◽  
Mohd Moshahid Alam Rizvi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Particle Size ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Cancer Cell Line ◽  
Entrapment Efficiency ◽  
Plga Nanoparticles ◽  
Cancer Management ◽  
Mcf 7

In the present study, thymoquinone (TQ)-encapsulated chitosan- (CS)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were formulated using the emulsion evaporation method. NPs were optimized by using 33-QbD approach for improved efficacy against breast cancer. The optimized thymoquinone loaded chitosan coated Poly (d,l-lactide-co-glycolide) nanoparticles (TQ-CS-PLGA-NPs) were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The surface coating of PLGA-NPs was completed by CS coating and there were no significant changes in particle size and entrapment efficiency (EE) observed. The developed TQ-CS-PLGA-NPs showed particle size, polydispersibility index (PDI), and %EE in the range between 126.03–196.71 nm, 0.118–0.205, and 62.75%–92.17%. The high and prolonged TQ release rate was achieved from TQ-PLGA-NPs and TQ-CS-PLGA-NPs. The optimized TQ-CS-PLGA-NPs showed significantly higher mucoadhesion and intestinal permeation compared to uncoated TQ-PLGA-NPs and TQ suspension. Furthermore, TQ-CS-PLGA-NPs showed statistically enhanced antioxidant potential and cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated TQ-PLGA-NPs and pure TQ. On the basis of the above findings, it may be stated that chitosan-coated TQ-PLGA-NPs represent a great potential for breast cancer management.

scholarly journals Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1379 ◽  
Author(s):  
Sarah Stewart ◽  
Juan Domínguez-Robles ◽  
Ryan Donnelly ◽  
Eneko Larrañeta
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Patient Compliance ◽  
Oral Delivery ◽  
Oral Route ◽  
Clinical Applications ◽  
Drug Concentrations ◽  
Effective Delivery ◽  
Materials Used ◽  
Drug Delivery Devices

The oral route is a popular and convenient means of drug delivery. However, despite its advantages, it also has challenges. Many drugs are not suitable for oral delivery due to: first pass metabolism; less than ideal properties; and side-effects of treatment. Additionally, oral delivery relies heavily on patient compliance. Implantable drug delivery devices are an alternative system that can achieve effective delivery with lower drug concentrations, and as a result, minimise side-effects whilst increasing patient compliance. This article gives an overview of classification of these drug delivery devices; the mechanism of drug release; the materials used for manufacture; the various methods of manufacture; and examples of clinical applications of implantable drug delivery devices.

scholarly journals Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2920
Author(s):  
Ameeduzzafar Zafar ◽  
Syed Sarim Imam ◽  
Nabil K. Alruwaili ◽  
Omar Awad Alsaidan ◽  
Mohammed H. Elkomy ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
System Optimization ◽  
Globule Size

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

scholarly journals Heterogeneous expression of Pil3 pilus is critical for Streptococcus gallolyticus translocation across polarized colonic epithelial monolayers

2019 ◽  
Author(s):  
Mariana Martins ◽  
Laurence du Merle ◽  
Patrick Trieu-Cuot ◽  
Shaynoor Dramsi
Keyword(s):  
Intestinal Barrier ◽  
Opportunistic Pathogen ◽  
Oral Route ◽  
Elderly Persons ◽  
Dependent Manner ◽  
Bacterial Surface ◽  
Streptococcus Gallolyticus ◽  
Heterogeneous Expression ◽  
Colonic Cells

ABSTRACTStreptococcus gallolyticus subspecies gallolyticus (Sgg) is an opportunistic pathogen responsible for septicaemia and endocarditis in elderly persons. Sgg is also a commensal of the human gastrointestinal tract. Here we demonstrate that Sgg strain UCN34 translocates across tight intestinal barriers in vitro in a Pil3-dependent manner. Confocal images of UCN34 passage across human colonic cells reveals that Sgg utilizes a paracellular pathway. Pil3 was previously shown to be expressed heterogeneously and WT UCN34 consists of about 90% of Pil3low and 10% of Pil3high cells. We found that both the Δpil3 mutant and the Pil3+ overexpressing variant could not translocate across Caco-2 and T84 barriers. Interestingly, combining live Δpil3 mutant cells with fixed Pil3+ variants in a 10:1 ratio (mimicking UCN34 WT population) allowed efficient translocation of the Δpil3 mutant. These experiments demonstrate that heterogeneous expression of Pil3 plays a key role in optimal translocation of Sgg across the intestinal barrier.ABSTRACT IMPORTANCEStreptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen responsible for septicemia and infective endocarditis in elderly persons. Sgg is a commensal of the rumen of herbivores and transmission to humans most probably occurs through the oral route. In this work, we have studied how this bacterium crosses the intestinal barrier using well-known in vitro models. Confocal microscopy images revealed that Sgg UCN34 can traverse the epithelial monolayer in between adjacent cells. We next showed that passage of Sgg from the apical to the basolateral compartment is dependent on the heterogenous expression of the Pil3 pilus at the bacterial surface. We hypothesize that Pil3high cocci adhere firmly to epithelial cells to activate transient opening of tight junctions thereby allowing the traversal of Pil3low bacteria.

New and novel approaches for enhancing the oral absorption and bioavailability of protein and peptides therapeutics

2020 ◽  
Vol 11 (11) ◽  
pp. 713-732
Author(s):  
Abhishek Kanugo ◽  
Ambikanandan Misra
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Enzyme Inhibitors ◽  
Oral Route ◽  
Limited Success ◽  
Physical Chemical ◽  
Novel Approaches ◽  
Active Research

The advancement of the oral route for macromolecules has gained a lot of attention due to its noninvasive nature, safe and challenging in active research but with limited success. Oral administration poses challenges due to poor solubility, short half-life, quick elimination and the physical, chemical and biological barriers of the gastrointestinal tract. Approaches of past for improving oral absorption, such as enhancers, mucoadhesive delivery and enzyme inhibitors have been taken over by novel approaches like advanced liposomes, self-nanoemulsifying drug delivery system, nanoparticles and targeted delivery. Eudratech™ Pep, Peptelligence, Rani Pill and Pharm Film are the emerging technologies for delivering oral proteins and peptide. Calcitonin, semaglutide and octreotide are the peptides available in the market for oral delivery as outcomes of these technologies.

scholarly journals Toxicity of Carbon Nanomaterials and Their Potential Application as Drug Delivery Systems: In Vitro Studies in Caco-2 and MCF-7 Cell Lines

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1617
Author(s):  
Rosa Garriga ◽  
Tania Herrero-Continente ◽  
Miguel Palos ◽  
Vicente L. Cebolla ◽  
Jesús Osada ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Graphene Oxide ◽  
Carbon Nanomaterials ◽  
Chemotherapeutic Agents ◽  
Breast Adenocarcinoma ◽  
In Vitro Toxicity ◽  
Carbon Nanomaterial ◽  
Carbon Nanohorns ◽  
Mcf 7

Carbon nanomaterials have attracted increasing attention in biomedicine recently to be used as drug nanocarriers suitable for medical treatments, due to their large surface area, high cellular internalization and preferential tumor accumulation, that enable these nanomaterials to transport chemotherapeutic agents preferentially to tumor sites, thereby reducing drug toxic side effects. However, there are widespread concerns on the inherent cytotoxicity of carbon nanomaterials, which remains controversial to this day, with studies demonstrating conflicting results. We investigated here in vitro toxicity of various carbon nanomaterials in human epithelial colorectal adenocarcinoma (Caco-2) cells and human breast adenocarcinoma (MCF-7) cells. Carbon nanohorns (CNH), carbon nanotubes (CNT), carbon nanoplatelets (CNP), graphene oxide (GO), reduced graphene oxide (GO) and nanodiamonds (ND) were systematically compared, using Pluronic F-127 dispersant. Cell viability after carbon nanomaterial treatment followed the order CNP < CNH < RGO < CNT < GO < ND, being the effect more pronounced on the more rapidly dividing Caco-2 cells. CNP produced remarkably high reactive oxygen species (ROS) levels. Furthermore, the potential of these materials as nanocarriers in the field of drug delivery of doxorubicin and camptothecin anticancer drugs was also compared. In all cases the carbon nanomaterial/drug complexes resulted in improved anticancer activity compared to that of the free drug, being the efficiency largely dependent of the carbon nanomaterial hydrophobicity and surface chemistry. These fundamental studies are of paramount importance as screening and risk-to-benefit assessment towards the development of smart carbon nanomaterial-based nanocarriers.

scholarly journals GASTRORETENTIVE DRUG DELIVERY SYSTEMS: FROM CONCEPTION TO COMMERCIAL SUCCESS

2017 ◽  
Vol 4 (2) ◽  
pp. 10 ◽  
Author(s):  
Harshil P. Shah ◽  
Shailesh T. Prajapati ◽  
C. N. Patel
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Oral Route ◽  
Delivery Systems ◽  
Present Review ◽  
Gastric Residence Time ◽  
In Vivo Characterization ◽  
Absorption Window

Despite the extensive advancements in the field of drug delivery, the oral route remains the favorable route for administration of therapeutic actives. A success of oral controlled drug delivery systems is associated with reduced dosing frequency, decreased fluctuation in plasma drug concentration profile along with improved patient compliance. However, they are also associated with challenges like shorter gastric residence time, unpredictable gastric emptying and poor bioavailability for some molecules. This has initiated tremendous advancements in the field of gastro-retention to achieve controlled release of drugs along with improved bioavailability of drugs with narrow absorption window as well as localized action in the stomach and upper part of GIT. In present review, efforts have been envisaged to summarize our current understanding in the field of gastro-retention and their in vitro as well as in vivo characterization. Present review also highlights commercially utilized gastro-retentive technologies and some recently granted US patents in the field of GRDDS.

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