Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives

The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed.

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Computer-Aided Discovery of New Solubility-Enhancing Drug Delivery System

Biomolecules ◽

10.3390/biom10060913 ◽

2020 ◽

Vol 10 (6) ◽

pp. 913

Author(s):

Mikołaj Mizera ◽

Eugene N. Muratov ◽

Vinicius M. Alves ◽

Alexander Tropsha ◽

Judyta Cielecka-Piontek

Keyword(s):

Therapeutic Potential ◽

Aqueous Solubility ◽

Cefuroxime Axetil ◽

Structure Property ◽

Pharmaceutical Ingredients ◽

Structure Property Relationship ◽

Poorly Soluble ◽

The Stability ◽

First Time ◽

Poor Stability

The poor aqueous solubility of active pharmaceutical ingredients (APIs) places a limit on their therapeutic potential. Cyclodextrins (CDs) have been shown to improve the solubility of APIs, but the magnitude of the improvement depends on the structure of both the CDs and APIs. We have developed quantitative structure–property relationship (QSPR) models that predict the stability of the complexes formed by a popular poorly soluble antibiotic, cefuroxime axetil (CA) and different CDs. We applied this model to five CA–CD systems not included in the modeling set. Two out of three systems predicted to have poor stability and poor CA solubility, and both CA–CD systems predicted to have high stability and high CA solubility were confirmed experimentally. One of the CDs that significantly improved CA solubility, methyl-βCD, is described here for the first time, and we propose this CD as a novel promising excipient. Computational approaches and models developed and validated in this study could help accelerate the development of multifunctional CDs-based formulations.

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Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.5.7 ◽

2020 ◽

Vol 13 (5) ◽

pp. 5102-5109

Author(s):

Venu Madhav K ◽

Somnath De ◽

Chandra Shekar Bonagiri ◽

Sridhar Babu Gummadi

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Solid Dispersions ◽

In Vitro Release ◽

Aqueous Solubility ◽

Water Soluble ◽

Scanning Calorimetry ◽

In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension. From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

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Strategies for Oral Delivery of Metal-Saturated Lactoferrin

Current Protein and Peptide Science ◽

10.2174/1389203720666190513085839 ◽

2019 ◽

Vol 20 (11) ◽

pp. 1046-1051 ◽

Cited By ~ 1

Author(s):

Przemysław Gajda-Morszewski ◽

Klaudyna Śpiewak-Wojtyła ◽

Maria Oszajca ◽

Małgorzata Brindell

Keyword(s):

Biological Activity ◽

Oral Delivery ◽

Therapeutic Potential ◽

Structure And Function ◽

The Difference ◽

And Function ◽

First Time

Lactoferrin was isolated and purified for the first time over 50-years ago. Since then, extensive studies on the structure and function of this protein have been performed and the research is still being continued. In this mini-review we focus on presenting recent scientific efforts towards the elucidation of the role and therapeutic potential of lactoferrin saturated with iron(III) or manganese(III) ions. The difference in biological activity of metal-saturated lactoferrin vs. the unmetalated one is emphasized. The strategies for oral delivery of lactoferrin, are also reviewed, with particular attention to the metalated protein.

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The Potential of Milk-derived Exosomes for Drug Delivery

Current Drug Delivery ◽

10.2174/1567201817666200817112503 ◽

2020 ◽

Vol 17 ◽

Author(s):

Shuyuan Li ◽

Yue Tang ◽

Yushun Dou

Keyword(s):

Drug Delivery ◽

Oral Delivery ◽

Therapeutic Potential ◽

Current Knowledge ◽

Biological Fluids ◽

Drug Loading ◽

Drug Carriers ◽

Current Application ◽

Therapeutic Benefits ◽

Loading Methods

Background: Exosomes, one of the extracellular vesicles, are widely present in all biological fluids and play an important role in intercellular communication. Because of its hydrophobic lipid bilayer and aqueous hydrophilic core structure, it is considered a possible alternative to liposome drug delivery systems. Not only do they protect the cargo like liposomes during delivery, they are less toxic and better tolerated. However, due to the lack of sources and methods for obtaining enough exosomes, the therapeutic application of exosomes as drug carriers is limited. Methods: A literature search was performed using the ScienceDirect and PubMed electronic databases to obtain information from published literature on milk exosomes related to drug delivery. Results: Here, we briefly reviewed the current knowledge of exosomes, expounded the advantages of milk-derived exosomes over other delivery vectors, including a higher yield, the oral delivery characteristic and additional therapeutic benefits. The purification and drug loading methods of milk exosomes, and the current application of milk exosomes were also introduced. Conclusion: The emergence of milk-derived exosomes is expected to break through the limitations of exosomes as therapeutic carriers of drugs. We hope to raise awareness of the therapeutic potential of milk-derived exosomes as a new drug delivery system.

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Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential

Plants ◽

10.3390/plants10020400 ◽

2021 ◽

Vol 10 (2) ◽

pp. 400

Author(s):

Henry Lowe ◽

Blair Steele ◽

Joseph Bryant ◽

Ngeh Toyang ◽

Wilfred Ngwa

Keyword(s):

Secondary Metabolites ◽

Cannabis Sativa ◽

Therapeutic Potential ◽

Physiological Activity ◽

Economic Value ◽

Therapeutic Window ◽

Future Directions ◽

Medicinal Properties ◽

The Many ◽

Human Viruses

The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites—Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

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Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽

10.3390/nu11092147 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2147 ◽

Cited By ~ 42

Author(s):

Michele Dei Cas ◽

Riccardo Ghidoni

Keyword(s):

Small Intestine ◽

Cellular Uptake ◽

Oral Delivery ◽

Therapeutic Potential ◽

Pharmacokinetic Profile ◽

Yellow Pigment ◽

The Body ◽

Anti Cancer ◽

Poor Absorption ◽

Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

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Non-Cannabinoid Metabolites of Cannabis sativa with Therapeutic Potential

10.20944/preprints202010.0551.v2 ◽

2020 ◽

Author(s):

Henry Lowe ◽

Blair Steele ◽

Joseph Bryant ◽

Ngeh Toyang ◽

Wilfred Ngwa

Keyword(s):

Secondary Metabolites ◽

Cannabis Sativa ◽

Therapeutic Potential ◽

Physiological Activity ◽

Economic Value ◽

Therapeutic Window ◽

Future Directions ◽

Medicinal Properties ◽

The Many ◽

Human Viruses

The Cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most prominent and most studied secondary metabolites— Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus SARS-COV2, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

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Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration

Pharmaceutics ◽

10.3390/pharmaceutics11110561 ◽

2019 ◽

Vol 11 (11) ◽

pp. 561 ◽

Cited By ~ 1

Author(s):

Maharjan ◽

Kim ◽

Jin ◽

Ko ◽

Song ◽

...

Keyword(s):

Macular Degeneration ◽

Oral Delivery ◽

Water Solubility ◽

Vision Loss ◽

Oral Absorption ◽

Aqueous Solubility ◽

Oral Formulation ◽

Preclinical Study ◽

Age Related Macular Degeneration ◽

Age Related

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.

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Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment

Cancers ◽

10.3390/cancers12020522 ◽

2020 ◽

Vol 12 (2) ◽

pp. 522 ◽

Cited By ~ 4

Author(s):

Vanessa T. Chivere ◽

Pierre P. D. Kondiah ◽

Yahya E. Choonara ◽

Viness Pillay

Keyword(s):

Oral Delivery ◽

Oral Drug Delivery ◽

Specific Binding ◽

Biological Effects ◽

Aqueous Solubility ◽

Oral Route ◽

Oral Drug ◽

Cancer Drugs ◽

Anti Cancer ◽

Route Of Delivery

Routes of drug administration and their corresponding physiochemical characteristics play major roles in drug therapeutic efficiency and biological effects. Each route of delivery has favourable aspects and limitations. The oral route of delivery is the most convenient, widely accepted and safe route. However, the oral route of chemotherapeutics to date have displayed high gastric degradation, low aqueous solubility, poor formulation stability and minimum intestinal absorption. Thus, mainstream anti-cancer drugs in current formulations are not suitable as oral chemotherapeutic formulations. The use of biopolymers such as chitosan, gelatin, hyaluronic acid and polyglutamic acid, for the synthesis of oral delivery platforms, have potential to help overcome problems associated with oral delivery of chemotherapeutics. Biopolymers have favourable stimuli-responsive properties, and thus can be used to improve oral bioavailability of anti-cancer drugs. These biopolymeric formulations can protect gastric-sensitive drugs from pH degradation, target specific binding sites for targeted absorption and consequently control drug release. In this review, the use of various biopolymers as oral drug delivery systems for chemotherapeutics will be discussed.

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MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Genes ◽

10.3390/genes10100752 ◽

2019 ◽

Vol 10 (10) ◽

pp. 752 ◽

Cited By ~ 11

Author(s):

Rawat ◽

Kadian ◽

Gupta ◽

Kumar ◽

Chain ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Therapeutic Potential ◽

Critical Role ◽

Mirna Biogenesis ◽

Effective Management ◽

Future Directions ◽

Novel Therapeutic Strategies ◽

Conclusion Section

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.

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