Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids.

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Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics12121194 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1194

Author(s):

Aristote B. Buya ◽

Ana Beloqui ◽

Patrick B. Memvanga ◽

Véronique Préat

Keyword(s):

Drug Delivery ◽

Patient Compliance ◽

Oral Delivery ◽

Drug Delivery Systems ◽

Water Solubility ◽

Oral Drug Delivery ◽

Delivery Systems ◽

Oral Drug ◽

Statistical Design Of Experiments

Approximately one third of newly discovered drug molecules show insufficient water solubility and therefore low oral bio-availability. Self-nano-emulsifying drug-delivery systems (SNEDDSs) are one of the emerging strategies developed to tackle the issues associated with their oral delivery. SNEDDSs are composed of an oil phase, surfactant, and cosurfactant or cosolvent. SNEDDSs characteristics, their ability to dissolve a drug, and in vivo considerations are determinant factors in the choice of SNEDDSs excipients. A SNEDDS formulation can be optimized through phase diagram approach or statistical design of experiments. The characterization of SNEDDSs includes multiple orthogonal methods required to fully control SNEDDS manufacture, stability, and biological fate. Encapsulating a drug in SNEDDSs can lead to increased solubilization, stability in the gastro-intestinal tract, and absorption, resulting in enhanced bio-availability. The transformation of liquid SNEDDSs into solid dosage forms has been shown to increase the stability and patient compliance. Supersaturated, mucus-permeating, and targeted SNEDDSs can be developed to increase efficacy and patient compliance. Self-emulsification approach has been successful in oral drug delivery. The present review gives an insight of SNEDDSs for the oral administration of both lipophilic and hydrophilic compounds from the experimental bench to marketed products.

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In Vitro Production and Exudation of 20-Hydroxymaytenin from Gymnosporia heterophylla (Eckl. and Zeyh.) Loes. Cell Culture

Plants ◽

10.3390/plants10081493 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1493

Author(s):

Thanet Pitakbut ◽

Michael Spiteller ◽

Oliver Kayser

Keyword(s):

Biological Activities ◽

Quinone Methide ◽

Induction Medium ◽

Naphthalene Acetic Acid ◽

In Vitro Production ◽

Pentacyclic Triterpenoids ◽

Anticancer Properties ◽

Vitro Production ◽

First Time

The metabolite 20-Hydroxymaytenin (20-HM) is a member of the quinone-methide pentacyclic triterpenoids (QMTs) group. This metabolite group is present only in Celastraceae plants, and it has shown various biological activities from antioxidant to anticancer properties. However, most QMTs metabolites including 20-HM cannot be synthesized in a laboratory. Therefore, we optimized a plant tissue culture protocol and examined the potential of Gymnosporia heterophylla (synonym. Maytenus heterophylla) to produce 20-HM in an in vitro experiment. For the first time, we reported the optimum callus induction medium with a high percentage success rate of 82% from the combination of 1 mg/L indole-3-butyric acid and 5 mg/L naphthalene acetic acid. Later, our cell suspension culture cultivated in the optimum medium provided approximately 0.35 mg/g fresh weight of 20-HM. This concentration is roughly 87.5 times higher than a concentration of 20-HM presenting in Elaeodendron croceum (Celastraceae) leaves. In addition, we also found that 20-HM presented in a cultivation medium, suggesting that G. heterophylla cells secreted 20-HM as an exudate in our experiment. Noticeably, 20-HM was missing when Penicillium cf. olsonii occurred in the medium. These findings hint at an antifungal property of 20-HM.

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Plant Extracts Loaded in Nanostructured Drug Delivery Systems for Treating Parasitic and Antimicrobial Diseases

Current Pharmaceutical Design ◽

10.2174/1381612825666190628153755 ◽

2019 ◽

Vol 25 (14) ◽

pp. 1604-1615 ◽

Cited By ~ 2

Author(s):

Brenna L.C. Gondim ◽

João A. Oshiro-Júnior ◽

Felipe H.A. Fernanandes ◽

Fernanda P. Nóbrega ◽

Lúcio R.C. Castellano ◽

...

Keyword(s):

Drug Delivery ◽

Plant Extracts ◽

Drug Delivery Systems ◽

Biological Activities ◽

Delivery Systems ◽

Active Components ◽

Current Therapies ◽

The Stability

Background: Plant extracts loaded in nanostructured drug delivery systems (NDDSs) have been reported as an alternative to current therapies for treating parasitic and antimicrobial diseases. Among their advantages, plant extracts in NDSSs increase the stability of the drugs against environmental factors by promoting protection against oxygen, humidity, and light, among other factors; improve the solubility of hydrophobic compounds; enhance the low absorption of the active components of the extracts (i.e., biopharmaceutical classification II), which results in greater bioavailability; and control the release rate of the substances, which is fundamental to improving the therapeutic effectiveness. In this review, we present the most recent data on NDDSs using plant extracts and report results obtained from studies related to in vitro and in vivo biological activities.

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Strategies to Improve Resveratrol Systemic and Topical Bioavailability: An Update

Antioxidants ◽

10.3390/antiox8080244 ◽

2019 ◽

Vol 8 (8) ◽

pp. 244 ◽

Cited By ~ 31

Author(s):

Sebastiano Intagliata ◽

Maria N. Modica ◽

Ludovica M. Santagati ◽

Lucia Montenegro

Keyword(s):

Water Solubility ◽

Biological Activities ◽

Biological Effects ◽

Radical Scavenging ◽

Topical Administration ◽

In Vivo Studies ◽

Biochemical Mechanisms ◽

Free Radical Scavenging Activities

In recent years, a great deal of attention has been paid to natural compounds due to their many biological effects. Polyphenols are a class of plant derivatives that have been widely investigated for preventing and treating many oxidative stress-related pathological conditions, such as neurodegenerative and cardiovascular diseases, cancer, diabetes mellitus and inflammation. Among these polyphenols, resveratrol (RSV) has attracted considerable interest owing to its high antioxidant and free radical scavenging activities. However, the poor water solubility and rapid metabolism of RSV lead to low bioavailability, thus limiting its clinical efficacy. After discussing the main biochemical mechanisms involved in RSV biological activities, this review will focus on the strategies attempted to improve RSV effectiveness, both for systemic and for topical administration. In particular, technological approaches involving RSV incorporation into different delivery systems such as liposomes, polymeric and lipid nanoparticles, microemulsions and cyclodextrins will be illustrated, highlighting their potential clinical applications. In addition, chemical modifications of this antioxidant aimed at improving its physicochemical properties will be described along with the results of in vitro and in vivo studies.

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Antithrombotic activity of LB30057, a newly synthesized direct thrombin inhibitor

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613549 ◽

2003 ◽

Vol 89 (01) ◽

pp. 104-111 ◽

Cited By ~ 1

Author(s):

Kyu-Tae Kang ◽

Byoung-In Jung ◽

Ok-Nam Bae ◽

Moo-Yeol Lee ◽

Seung-Min Chung ◽

...

Keyword(s):

Water Solubility ◽

Biological Activities ◽

High Water ◽

Human Platelets ◽

Thrombin Inhibitor ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Serotonin Secretion ◽

In Vivo Animal Model

SummaryAn amidrazonophenylalanine derivative, LB30057, inhibits the catalytic activity of thrombin potently by interaction with the active site of thrombin, and has high water solubility. In the present study, we evaluated the effect of LB30057 on the biological activities of thrombin at various tissues, and determined whether thrombin inhibition by LB30057 could reduce the incidence of occlusive thrombosis in an in vivo animal model. Treatment with LB30057 to human plasma prolonged clotting times in a concentration-dependent manner. LB30057 suppressed significantly thrombin-induced phosphatidylserine (PS) exposure in platelets, suggesting that LB30057 could inhibit blood coagulation accelerated by PS exposure. In human platelets, soluble thrombin- and clot-induced platelet aggregation was inhibited by LB30057 potently. Consistent with this finding, LB30057 showed concentration-dependent inhibitory effects on serotonin secretion and P-selectin expression induced by thrombin in platelets. In the blood vessel isolated from the guinea pig, treatment with LB30057 resulted in a concentration-dependent inhibition of thrombin-induced vascular contraction. In vivo study revealed that LB30057 following oral administration significantly increased the time to occlusion and improved carotid arterial patency using rat carotid artery thrombosis model. All these results suggest that LB30057 is a potent inhibitor of biological activities of thrombin at various target tissues and, therefore, might be developed as an anti-thrombotic agent for treatment and prevention of thrombotic diseases.

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Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

Molecules ◽

10.3390/molecules26144212 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4212

Author(s):

Kittisak Likhitwitayawuid

Keyword(s):

Water Solubility ◽

Biological Activities ◽

Delivery Systems ◽

Protective Effects ◽

Pharmacological Activities ◽

Plant Materials ◽

Research Attention ◽

Pharmacokinetic Properties ◽

Simple Chemical ◽

Oral Availability

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

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Potential Role of Garcinol as an Anticancer Agent

Journal of Oncology ◽

10.1155/2012/647206 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 36

Author(s):

Nadia Saadat ◽

Smiti V. Gupta

Keyword(s):

Potential Role ◽

Therapeutic Potential ◽

Biological Activities ◽

Tropical Regions ◽

Anticancer Properties ◽

Garcinia Indica ◽

Scientific Investigations

Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit ofGarcinia indica, a plant found extensively in tropical regions. Although the fruit has been consumed traditionally over centuries, its biological activities, specifically its anticancer potential is a result of recent scientific investigations. The anticarcinogenic properties of garcinol appear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, and proapoptotic activities. In addition, garcinol displays effective epigenetic influence by inhibiting histone acetyltransferases (HAT 300) and by possible posttranscriptional modulation by mi RNA profiles involved in carcinogenesis.In vitroas well as somein vivostudies have shown the potential of this compound against several cancers types including breast, colon, pancreatic, and leukemia. Although this is a promising molecule in terms of its anticancer properties, investigations in relevant animal models, and subsequent human trials are warranted in order to fully appreciate and confirm its chemopreventative and/or therapeutic potential.

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Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems

Polymers ◽

10.3390/polym10030267 ◽

2018 ◽

Vol 10 (3) ◽

pp. 267 ◽

Cited By ~ 126

Author(s):

Twana M. Ways ◽

Wing Lau ◽

Vitaliy Khutoryanskiy

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Water Solubility ◽

Enzyme Inhibitors ◽

Ethylenediaminetetraacetic Acid ◽

Delivery Systems ◽

Sustained Drug Release ◽

Glycol Chitosan ◽

Synthetic Approaches

Mucoadhesive drug delivery systems are desirable as they can increase the residence time of drugs at the site of absorption/action, provide sustained drug release and minimize the degradation of drugs in various body sites. Chitosan is a cationic polysaccharide that exhibits mucoadhesive properties and it has been widely used in the design of mucoadhesive dosage forms. However, its limited mucoadhesive strength and limited water-solubility at neutral and basic pHs are considered as two major drawbacks of its use. Chemical modification of chitosan has been exploited to tackle these two issues. In this review, we highlight the up-to-date studies involving the synthetic approaches and description of mucoadhesive properties of chitosan and chitosan derivatives. These derivatives include trimethyl chitosan, carboxymethyl chitosan, thiolated chitosan, chitosan-enzyme inhibitors, chitosan-ethylenediaminetetraacetic acid (chitosan-EDTA), half-acetylated chitosan, acrylated chitosan, glycol chitosan, chitosan-catechol, methyl pyrrolidinone-chitosan, cyclodextrin-chitosan and oleoyl-quaternised chitosan. We have particularly focused on the effect of chemical derivatization on the mucoadhesive properties of chitosan. Additionally, other important properties including water-solubility, stability, controlled release, permeation enhancing effect, and in vivo performance are also described.

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Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?

Pharmaceutics ◽

10.3390/pharmaceutics13081180 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1180

Author(s):

Giovanna Rassu ◽

Milena Sorrenti ◽

Laura Catenacci ◽

Barbara Pavan ◽

Luca Ferraro ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Biological Activities ◽

Detailed Examination ◽

Delivery Systems ◽

Nasal Drug Delivery ◽

In Vivo Models ◽

Nasal Application

Cyclodextrins (CDs) are oligosaccharides widely used in the pharmaceutical field. In this review, a detailed examination of the literature of the last two decades has been made to understand the role of CDs in nasal drug delivery systems. In nasal formulations, CDs are used as pharmaceutical excipients, as solubilizers and absorption promoters, and as active ingredients due to their several biological activities (antiviral, antiparasitic, anti-atherosclerotic, and neuroprotective). The use of CDs in nasal formulations allowed obtaining versatile drug delivery systems intended for local and systemic effects, as well as for nose-to-brain transport of drugs. In vitro and in vivo models currently employed are suitable to analyze the effects of CDs in nasal formulations. Therefore, CDs are versatile pharmaceutical materials, and due to the continual synthesis of new CDs derivatives, the research on the new nasal applications is an interesting field evolving in the coming years, to which Italian research will still contribute.

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Novel Micro- and Nanocellulose-Based Delivery Systems for Liposoluble Compounds

Nanomaterials ◽

10.3390/nano11102593 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2593

Author(s):

Francisca Casanova ◽

Carla F. Pereira ◽

Alessandra B. Ribeiro ◽

Ricardo Freixo ◽

Eduardo Costa ◽

...

Keyword(s):

Bioactive Compounds ◽

Water Solubility ◽

Biological Activities ◽

Aqueous Solubility ◽

Delivery Systems ◽

Great Promise ◽

Gastrointestinal Conditions ◽

Wide Range ◽

State Of Research ◽

The Impact

Poor aqueous solubility of bioactive compounds is becoming a pronounced challenge in the development of bioactive formulations. Numerous liposoluble compounds have very interesting biological activities, but their low water solubility, stability, and bioavailability restrict their applications. To overcome these limitations there is a need to use enabling delivering strategies, which often demand new carrier materials. Cellulose and its micro- and nanostructures are promising carriers with unique features. In this context, this review describes the fast-growing field of micro- and nanocellulose based delivery systems with a focus on the release of liposoluble bioactive compounds. The state of research on this field is reviewed in this article, which also covers the chemistry, preparation, properties, and applications of micro- and nanocellulose based delivery systems. Although there are promising perspectives for introducing these materials into various fields, aspects of safety and toxicity must be revealed and are discussed in this review. The impact of gastrointestinal conditions on the systems and on the bioavailability of the bioactive compounds are also addressed in this review. This article helps to unveil the whole panorama of micro- and nanocellulose as delivery systems for liposoluble compounds, showing that these represent a great promise in a wide range of applications.

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