Essential oils as anticancer agents: Potential role in malignancies, drug delivery mechanisms, and immune system enhancement

The recent success of checkpoint blocking antibodies has sparked a revolution in cancer immunotherapy. Checkpoint inhibition activates the adaptive immune system leading to durable responses across a range of tumor types, although this response is limited to patient populations with pre-existing tumor-infiltrating T cells. Strategies to stimulate the immune system to prime an antitumor response are of intense interest and several groups are now working to develop agents to activate the Pattern Recognition Receptors (PRRs), proteins which detect pathogenic and damageassociated molecules and respond by activating the innate immune response. Although early efforts focused on the Toll-like Receptor (TLR) family of membrane-bound PRRs, TLR activation has been associated with both pro- and antitumor effects. Nonetheless, TLR agonists have been deployed as potential anticancer agents in a range of clinical trials. More recently, the cytosolic PRR Stimulator of IFN Genes (STING) has attracted attention as another promising target for anticancer drug development, with early clinical data beginning to emerge. Besides STING, several other cytosolic PRR targets have likewise captured the interest of the drug discovery community, including the RIG-Ilike Receptors (RLRs) and NOD-like Receptors (NLRs). In this review, we describe the outlook for activators of PRRs as anticancer therapeutic agents and contrast the earlier generation of TLR agonists with the emerging focus on cytosolic PRR activators, both as single agents and in combination with other cancer immunotherapies.

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Nanostructured Lipid Carriers (NLCs) for drug delivery: Role of Liquid lipid (oil)

Current Drug Delivery ◽

10.2174/1567201817666200423083807 ◽

2020 ◽

Vol 17 ◽

Author(s):

Anisha D’Souza ◽

Ranjita Shegokar

Keyword(s):

Drug Delivery ◽

Essential Oils ◽

Drug Carrier ◽

Drug Loading ◽

Performance Criteria ◽

Long Term Stability ◽

Natural Oils ◽

Optimal Drug

: In recent years, SLNs and NLCs are among the popular drug delivery systems studied for delivery of lipophilic drugs. Both systems have demonstrated several beneficial properties as an ideal drug-carrier, optimal drug-loading and good long-term stability. NLCs are getting popular due to their stability advantages and possibility to load various oil components either as an active or as a matrix. This review screens types of oils used till date in combination with solid lipid to form NLCs. These oils are broadly classified in two categories: Natural oils and Essential oils. NLCs offer range advantages in drug delivery due to the formation of imperfect matrix owing to the presence of oil. The type and percentage of oil used determines optimal drug loading and stability. Literature shows that variety of oils is used in NLCs mainly as matrix, which is from natural origin, triglycerides class. On the other hand, essential oils not only serve as a matrix but as an active. In short, oil is the key ingredient in formation of NLCs, hence needs to be selected wisely as per the performance criteria expected.

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Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200811124013 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sahil Kumar ◽

Bandna Sharma ◽

Tilak R. Bhardwaj ◽

Rajesh K. Singh

Keyword(s):

Drug Delivery ◽

Colon Cancer ◽

Drug Release ◽

Anticancer Agents ◽

Release Kinetics ◽

In Vitro Release ◽

Specific Treatment ◽

Drug Conjugates ◽

Polymer Drug Conjugates

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.

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Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

Pharmaceutics ◽

10.3390/pharmaceutics12060544 ◽

2020 ◽

Vol 12 (6) ◽

pp. 544

Author(s):

Miao Wang ◽

Sung-Kyun You ◽

Hong-Ki Lee ◽

Min-Gu Han ◽

Hyeon-Min Lee ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Anticancer Agents ◽

Lipid Membrane ◽

Ex Vivo ◽

System Optimization ◽

Raw Material ◽

Phospholipid Complex ◽

Low Solubility

Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex (DTX@PLC), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, DTX@PLC-loaded SME (DTX@PLC-SME) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared DTX@PLC-SME by combining dual technologies, which are advantages for oral absorption. Next, we optimized DTX@PLC-SME with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that DTX@PLC-SME showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that DTX@PLC-SME improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that DTX@PLC-SME can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability.

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Drug Delivery: Design of a Novel Mesoporous Organosilica Hybrid Microcarrier: a pH Stimuli-Responsive Dual-Drug-Delivery Vehicle for Intracellular Delivery of Anticancer Agents (Part. Part. Syst. Charact. 12/2013)

Particle & Particle Systems Characterization ◽

10.1002/ppsc.201370046 ◽

2013 ◽

Vol 30 (12) ◽

pp. 999-999 ◽

Cited By ~ 1

Author(s):

Madhappan Santha Moorthy ◽

Jae-Ho Bae ◽

Mi-Ju Kim ◽

Sun-Hee Kim ◽

Chang-Sik Ha

Keyword(s):

Drug Delivery ◽

Anticancer Agents ◽

Intracellular Delivery ◽

Stimuli Responsive ◽

Delivery Vehicle ◽

Drug Delivery Vehicle ◽

Mesoporous Organosilica ◽

Dual Drug

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Haptoglobin and Its Related Protein, Zonulin—What Is Their Role in Spondyloarthropathy?

Journal of Clinical Medicine ◽

10.3390/jcm10051131 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1131

Author(s):

Magdalena Chmielińska ◽

Marzena Olesińska ◽

Katarzyna Romanowska-Próchnicka ◽

Dariusz Szukiewicz

Keyword(s):

Immune Response ◽

Free Radicals ◽

Immune System ◽

Potential Role ◽

Acute Phase Protein ◽

Related Protein ◽

Functional Differences ◽

Phase Protein ◽

Its Polymorphism

Haptoglobin (Hp) is an acute phase protein which supports the immune response and protects tissues from free radicals. Its concentration correlates with disease activity in spondyloarthropathies (SpAs). The Hp polymorphism determines the functional differences between Hp1 and Hp2 protein products. The role of the Hp polymorphism has been demonstrated in many diseases. In particular, the Hp 2-2 phenotype has been associated with the unfavorable course of some inflammatory and autoimmune disorders. Its potential role in modulating the immune system in SpA is still unknown. This article contains pathophysiological considerations on the potential relationship between Hp, its polymorphism and SpA.

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Doxorubicin Embedded into Nanofibrillated Bacterial Cellulose (NFBC) Produces a Promising Therapeutic Outcome for Peritoneally Metastatic Gastric Cancer in Mice Models via Intraperitoneal Direct Injection

Nanomaterials ◽

10.3390/nano11071697 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1697

Author(s):

Hidenori Ando ◽

Takashi Mochizuki ◽

Amr S. Abu Lila ◽

Shunsuke Akagi ◽

Kenji Tajima ◽

...

Keyword(s):

Gastric Cancer ◽

Drug Delivery ◽

Tumor Growth ◽

Bacterial Cellulose ◽

Anticancer Agents ◽

Intraperitoneal Administration ◽

In Vitro Release ◽

Xenograft Model ◽

Tumor Growth Inhibition

Natural materials such as bacterial cellulose are gaining interest for their use as drug-delivery vehicles. Herein, the utility of nanofibrillated bacterial cellulose (NFBC), which is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) in a medium supplemented with carboxymethylcellulose (CMC) that is referred to as CM-NFBC, is described. Recently, we demonstrated that intraperitoneal administration of paclitaxel (PTX)-containing CM-NFBC efficiently suppressed tumor growth in a peritoneally disseminated cancer xenograft model. In this study, to confirm the applicability of NFBC in cancer therapy, a chemotherapeutic agent, doxorubicin (DXR), embedded into CM-NFBC, was examined for its efficiency to treat a peritoneally disseminated gastric cancer via intraperitoneal administration. DXR was efficiently embedded into CM-NFBC (DXR/CM-NFBC). In an in vitro release experiment, 79.5% of DXR was released linearly into the peritoneal wash fluid over a period of 24 h. In the peritoneally disseminated gastric cancer xenograft model, intraperitoneal administration of DXR/CM-NFBC induced superior tumor growth inhibition (TGI = 85.5%) by day 35 post-tumor inoculation, compared to free DXR (TGI = 62.4%). In addition, compared with free DXR, the severe side effects that cause body weight loss were lessened via treatment with DXR/CM-NFBC. These results support the feasibility of CM-NFBC as a drug-delivery vehicle for various anticancer agents. This approach may lead to improved therapeutic outcomes for the treatment of intraperitoneally disseminated cancers.

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Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics13081151 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1151

Author(s):

Lu Tang ◽

Jing Li ◽

Qingqing Zhao ◽

Ting Pan ◽

Hui Zhong ◽

...

Keyword(s):

Drug Delivery ◽

Cancer Treatment ◽

Small Molecule ◽

Anticancer Agents ◽

Targeted Drug Delivery ◽

Treatment Modalities ◽

Biological Macromolecules ◽

Passive Targeting ◽

Efficient Delivery ◽

Targeted Drug

The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

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Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

Frontiers in Medicine ◽

10.3389/fmed.2021.745789 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mohammed M. Almutairi ◽

Farzane Sivandzade ◽

Thamer H. Albekairi ◽

Faleh Alqahtani ◽

Luca Cucullo

Keyword(s):

Immune System ◽

Molecular Mechanisms ◽

Potential Role ◽

Immune Cell ◽

Clinical Manifestations ◽

Cell Infiltration ◽

Cellular Mechanisms ◽

Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

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