Anticancer Drug Delivery Agent Research Articles

Enhancement of the efficacy of synthetic and natural anticancer agents through nanocarrier for colon cancer treatment

Colon cancer ranks third amongst type of cancer and second in terms of mortality. Various natural and synthetic anticancer agents have been used for the treatment of colon cancer. However, most anticancer agents have poor aqueous solubility and thus low absorptions and bioavailability. Moreover, the chemotherapeutic agents are unable to differentiate between normal and healthy cells and thus kill both types of cells. Nanocarriers have surfaced as a budding anticancer agent delivery system that could enhance the solubility and bioavailability of the anticancer agents and at the same time specifically deliver them to the cancerous cells. In this regard, gold, polymeric, and solid lipid nanoparticles, dendrimers, liposomes, niosomes, and carbon nanotubes have shown promising results as targeted anticancer drug delivery agents with enhanced bioavailability. The objective of this review article is to highlight these nanocarriers and present a detailed overview of how they have enhanced the efficacy of both synthetic and natural anticancer agents.

Biodegradable diblock copolymeric PEG-PCL nanoparticles: Synthesis, characterization and applications as anticancer drug delivery agents

Poly (ethylene glycol) methyl ether-block-poly (Ɛ-caprolactone) copolymers are useful biomedical materials owing to their amphiphilic nature, biodegradability, biocompatibility and also due to their semi-crystalline form having a low glass transition temperature. Due to their slow drug release profile, PEG-PCL copolymers are excellent candidates for sustained delivery applications over a period of time of more than a year. This unique property has provoked their relevance specially in the area of anticancer drug delivery applications in the form of various nanoaggregates like microspheres, nanogels, nanospheres, polymersomes, micelles, etc. A large variety of anticancer drugs/bioactives have been encapsulated in PEG-PCL copolymers for developing effective anticancer drug delivery systems and also for producing controlled drug release profiles. In recent times, PEG-PCL copolymers based nanoparticles have shown tremendous advancements as anticancer drug delivery vehicles owing to their higher drug loading capacities of the hydrophobic drugs, enhanced bioavailability, keeping away from being overpowered by way of phagocytes, decreased blasted discharge, and also in increasing the scattering time of drug within the blood stream during their systemic inoculation. These nano-formulated drug delivery systems can be used for the delivery of anticancer drugs at a specific site in a targeted approach. The developed nano-formulations possess promising potential in the treatment of cancer with improved anticancer efficacy and reduced toxicity invivo. In the current review, our main focus is to highlight the development and synthesis of different types of PEG-PCL copolymers (both conventional and greener approaches) along with the physico-chemical characterization techniques used primarily for the PEG-PCL co-polymeric systems. We have also summarized the uses of PEG-PCL co-polymeric nano formulations with various anticancer drugs as drug delivery platforms in the area of anticancer chemotherapy.

Green Synthesized Montmorillonite/Carrageenan/Fe3O4 Nanocomposites for pH-Responsive Release of Protocatechuic Acid and Its Anticancer Activity.

Discovery of a novel anticancer drug delivery agent is important to replace conventional cancer therapies which are often accompanied by undesired side effects. This study demonstrated the synthesis of superparamagnetic magnetite nanocomposites (Fe3O4-NCs) using a green method. Montmorillonite (MMT) was used as matrix support, while Fe3O4 nanoparticles (NPs) and carrageenan (CR) were used as filler and stabilizer, respectively. The combination of these materials resulted in a novel nanocomposite (MMT/CR/Fe3O4-NCs). A series of characterization experiments was conducted. The purity of MMT/CR/Fe3O4-NCs was confirmed by X-ray diffraction (XRD) analysis. High resolution transmission electron microscopy (HRTEM) analysis revealed the uniform and spherical shape of Fe3O4 NPs with an average particle size of 9.3 ± 1.2 nm. Vibrating sample magnetometer (VSM) analysis showed an Ms value of 2.16 emu/g with negligible coercivity which confirmed the superparamagnetic properties. Protocatechuic acid (PCA) was loaded onto the MMT/CR/Fe3O4-NCs and a drug release study showed that 15% and 92% of PCA was released at pH 7.4 and 4.8, respectively. Cytotoxicity assays showed that both MMT/CR/Fe3O4-NCs and MMT/CR/Fe3O4-PCA effectively killed HCT116 which is a colorectal cancer cell line. Dose-dependent inhibition was seen and the killing was enhanced two-fold by the PCA-loaded NCs (IC50–0.734 mg/mL) compared to the unloaded NCs (IC50–1.5 mg/mL). This study highlights the potential use of MMT/CR/Fe3O4-NCs as a biologically active pH-responsive drug delivery agent. Further investigations are warranted to delineate the mechanism of cell entry and cancer cell killing as well as to improve the therapeutic potential of MMT/CR/Fe3O4-NCs.

Structural and Functional Analysis of Pullulanase Type 1 (PulA) from Geobacillus thermopakistaniensis.

Pullulanase type I (PulA) is a debranching enzyme that specifically cleaves α-1,6-glycosidic linkages in pullulan. Pullulan has not only diverse applications in food industry but also has immune-stimulatory effects on B and T cells, and found to enhance the production of various anti-inflammatory cytokines in human. Moreover, pullulan has been suggested as a possible anti-cancer drug delivery agent without adjuvant due to its unique structure. The process of pullulan degradation is unresolved due to imprecise pullulanase structural characteristics. Therefore, the present study aimed to understand the structural and functional characteristics of pullulanase enzyme fromGeobacillus thermopakistaniensis MAS1 strain using various computational approaches. The physio-chemical topographies and secondary structure of GT_PulA were explored using ProPram, InterPro and SMART. Various tools like I-TASSER, ModRefiner, RAMPAGE, PROCHECK and MOE 2009.10 were used to construct and verify the 3D structural model. The structural elucidation confirmed the significant domains, i.e., CBM48, CBM2, and TIM barrel having catalytically active residues, and conserved region YNGWDP. CBM2 domain along with TIM barrel has a capacity to bind different ligands and proved favorable for multiple substrate catalyses. These structural properties can have a potential effect on enhancing enzymatic activity of GT_PulA enzyme.

Saponin loaded montmorillonite-human serum albumin nanocomposites as drug delivery system in colorectal cancer therapy

This study reports the synthesis and application of new saponin (SAP)-loaded montmorillonite-human serum albumin (Mt-HSA) nanocomposites (NCs) as an anticancer drug delivery agent. When the biodegradable and biofriendly HSA was combined with Mt., which possesses excellent mucoadhesive properties, the resulting NCs could pass through the gastrointestinal barrier easily. SAP-Mt-HSA NCs were prepared by a modified desolvation technique in which ethanol and glutaraldehyde (GA) were used as precipitating and crosslinking agents, respectively. The efficacy of these NCs was assessed in a colorectal cancer cell line (DLD-1) as an in-vitro gastrointestinal model and L929 fibroblast cells as a healthy cell model. The release profile of SAP and the cytotoxic effect and cellular uptake of NCs were evaluated. The results clearly demonstrated that SAP-Mt-HSA NCs can induce dose-dependent cancer cell death with little or no toxicity toward healthy cells.

Synthesis of supramolecular biodendrimeric β-CD-(spacer-β-CD)21 via click reaction and evaluation of its application as anticancer drug delivery agent

ABSTRACTThe per-β-CD dendrimer (10), having 21 β-CD residues connected to the core β-CD in the primary and secondary sides with encapsulation efficacy and β-CDs moiety to preserve the biocompatibility properties was synthesized using click reaction. The dendritic network and β-CD cavity of the obtained dendrimer were utilized to form a supramolecular compound via the formation of a host-guest inclusion complex with methotrexate (MTX) drug molecule. The MTT assay of compound 10 showed very low toxicity on T47D cancer cells. In vitro drug release investigation at pHs 7.4, 5, and 3 indicated that the release manner was remarkably pH dependent.

Fabrication of biodendrimeric β-cyclodextrin via click reaction with potency of anticancer drug delivery agent

The aim of this work was the synthesis of biodendrimeric β-cyclodextrin (β-CD) on the secondary face with encapsulation efficacy, with β-CDs moiety to preserve the biocompatibility properties, also particularly growth their loading capacity for drugs with certain size. The new dendrimer, having 14 β-CD residues attached to the core β-CD in secondary face (11), was prepared through click reaction. The encapsulation property of the prepared compound was evaluated by methotrexate (MTX) drug molecule. Characterization of compound 11 was performed with 1H NMR, 13C NMR and FTIR and its supramolecular inclusion complex structure was determined using FTIR, DLS, DSC and SEM techniques. In vitro cytotoxicity test results showed that compound 11 has very low or no cytotoxic effect on T47D cancer cells. In vitro drug release study at pHs 3, 5 and 7.4 showed that the release process was noticeably pH dependent and the dendrimer could be used as an appropriate controlled drug delivery system (DDS) for cancer treatment.

Uptake and clearance analysis of Technetium99m labelled iron oxide nanoparticles in a rabbit brain.

Nanoparticles as solid colloidal particles are extensively studied and used as anticancer drug delivery agents because of their physical properties. This current research aims to prepare water base suspension of uncoated iron oxide nanoparticles and their biodistribution study to different organs, especially the brain, by using a single photon emission computed tomography gamma camera. The water-based suspension of iron oxide nanoparticles was synthesised by a reformed version of the co-precipitation method and labelled with Tc99m for intravenous injection. The nanoparticles were injected without surface modification. X-ray diffraction (XRD), energy dispersive spectrometry (EDS) and transmission electron microscope (TEM) techniques were used for characterisation. Peaks of XRD and EDS indicate that the particles are magnetite and exist in aqueous suspension. The average diameter of iron oxide nanoparticles without any surface coating determined by TEM is 10 nm. These particles are capable of evading the reticuloendothelial system and can cross the blood-brain barrier in the rabbit. The labelling efficiency of iron oxide nanoparticles labelled with Tc99m is 85%, which is good for the biodistribution study. The sufficient amount of iron oxide nanoparticles concentration in the brain as compared with the surrounding soft tissues and their long blood retention time indicates that the water-based suspension of iron oxide nanoparticles may be an option for drug delivery into the brain.

Double Layered Hydroxides as Potential Anti-Cancer Drug Delivery Agents

The emergence of nanotechnology has changed the scenario of the medical world by revolutionizing the diagnosis, monitoring and treatment of cancer. This nanotechnology has been proved miraculous in detecting cancer cells, delivering chemotherapeutic agents and monitoring treatment from non-specific to highly targeted killing of tumor cells. In the past few decades, a number of inorganic materials have been investigated such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for examining their efficacy in targeting drug delivery. The reason behind the selection of these inorganic materials was their versatile and unique features efficient in drug delivery, such as wide availability, rich surface functionality, good biocompatibility, potential for target delivery, and controlled release of the drug from these inorganic nanomaterials. Although, the drug-LDH hybrids are found to be quite instrumental because of their application as advanced anti-cancer drug delivery systems, there has not been much research on them. This mini review is set to highlight the advancement made in the use of layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with the advantages of LDHs as anti-cancer drug delivery agents, the process of interaction of some of the common anti-cancer drugs with LDH has also been discussed.

Double Layered Hydroxides as Potential Anti-Cancer Drug Delivery Agents

Double Layered Hydroxides as Potential Anti-Cancer Drug Delivery Agents

Folate‐Conjugated Polymer Micelles with pH‐Triggered Drug Release Properties

Folate has been applied as a targeting moiety for various anticancer drug-delivery agents to avoid non-specific attack of normal tissues as well as to increase cellular uptake at the target tumor cells. Polymer micelles made of poly[(D,L-lactide)-co-glycolide)]-poly(ethylene glycol)-folate (PLGA-PEG-FOL) was fabricated as a tumor targeting carrier for encapsulating the anticancer drug doxorubicin. To accelerate the drug release in the endosome after folate-mediated cellular uptake, pH-sensitive poly(β-amino ester)-PEG-FOL (PAE-PEG-FOL) was added together with PLGA-PEG-FOL to form mixed micelles. The results showed that the drug release can be triggered at different pH due to the ionization of PAE. The IC(50) of PLGA-PEG-FOL micelles is 0.46 × 10(-6) M. With 20% PAE in the mixed micelles (20:80 mixed micelles), the IC(50) decreases to 0.34 × 10(-6) M, which is comparable to that of pure PAE-PEG-FOL micelles at pH 7.4. As a result of the pH sensitivity, the PAE-PEG-FOL micelles are not stable at pH 6.5 or lower, and the drug may be released from the micelles into the extracellular environment before uptake by the cells. The 20:80 mixed micelles are relatively stable at this condition. As a result, the micelles retain more drug in the micelles for a higher degree of cellular uptake by folate receptor-mediated endocytosis, and exhibit higher cytotoxicity.