A Critical Appraisal of Solubility Enhancement Techniques of Polyphenols

Polyphenols constitute a family of natural substances distributed widely in plant kingdom. These are produced as secondary metabolites by plants and so far 8000 representatives of this family have been identified. Recently, there is an increased interest in the polyphenols because of the evidence of their role in prevention of degenerative diseases such as neurodegenerative diseases, cancer, and cardiovascular diseases. Although a large number of drugs are available in the market for treatment of these diseases, however, the emphasis these days is on the exploitation of natural principles derived from plants. Most polyphenols show low in vivo bioavailability thus limiting their application for oral drug delivery. This low bioavailability could be associated with low aqueous solubility, first pass effect, metabolism in GIT, or irreversible binding to cellular DNA and proteins. Therefore, there is a need to devise strategies to improve oral bioavailability of polyphenols. Various approaches like nanosizing, self-microemulsifying drug delivery systems (SMEDDS), microencapsulation, complexation, and solid dispersion can be used to increase the bioavailability. This paper will highlight the various methods that have been employed till date for the solubility enhancement of various polyphenols so that a suitable drug delivery system can be formulated.

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Recent Advances in Liposomal Drug Delivery System of Quercetin for Cancer Targeting: A Mechanistic Approach

Current Drug Delivery ◽

10.2174/1567201817666200415112657 ◽

2020 ◽

Vol 17 (10) ◽

pp. 845-860 ◽

Cited By ~ 5

Author(s):

Sabya S. Das ◽

Afzal Hussain ◽

Priya R. Prasad Verma ◽

Syed S. Imam ◽

Mohammad A. Altamimi ◽

...

Keyword(s):

Drug Delivery ◽

Oral Drug Delivery ◽

Aqueous Solubility ◽

Free Radical Scavenger ◽

Oral Drug ◽

Radical Scavenger ◽

Solid Cancer ◽

Liposomal Drug

Quercetin (QT, 3,3′,4′,5,7-pentahydroxyflavone), is a natural flavonoid with nutritional value and acts as a potential free-radical scavenger (antioxidant). QT has also been explored for its anti-cancer as well as anti-proliferative activities against numerous cancerous cells. Moreover, QT exhibits significant pro-apoptotic activity against tumor cells and is well established to control the growth of different carcinoma cells at various phases of the cell cycle. Hence, it can reduce the burden of human solid cancer and metastasis. Both these activities have been established in a diverse class of human cell lines in-vitro as well as in animal models (in-vivo). Apart from the promising therapeutic activities of QT molecule, their applications have been limited due to some major concerns, including low oral bioavailability and poor aqueous solubility. Also, rapid gastrointestinal digestion of QT seems to be a key barrier for its clinical translations for oral drug delivery in conventional dosage form. Henceforth, to overcome these drawbacks, QT is loaded with liposomal systems, which exhibit promising outcomes in the upregulation of QT by the epithelial system and also improved its targeting at the site of action. Furthermore, Liposomes based Drug Delivery Systems (LDDS) have showed significant therapeutic activity with conjugated drug moiety and exhibit safety, biocompatibility, biodegradability, and mitigated toxicity despite having certain limitations associated with physiological and biological barriers. Herein, in this review, we have focused on the mechanism related with the chemotherapeutic activity of QT and also discussed the promising activity of QT-loaded LDDS as a potent chemotherapeutic agent for cancer therapy.

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In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms

Pharmaceutics ◽

10.3390/pharmaceutics11080416 ◽

2019 ◽

Vol 11 (8) ◽

pp. 416 ◽

Cited By ~ 3

Author(s):

Schneider ◽

Koziolek ◽

Weitschies

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Oral Drug Delivery ◽

Test Methods ◽

Delivery Systems ◽

Oral Drug ◽

Gastrointestinal Physiology ◽

In Vivo Test

More than 50 years ago, the first concepts for gastroretentive drug delivery systems were developed. Despite extensive research in this field, there is no single formulation concept for which reliable gastroretention has been demonstrated under different prandial conditions. Thus, gastroretention remains the holy grail of oral drug delivery. One of the major reasons for the various setbacks in this field is the lack of predictive in vitro and in vivo test methods used during preclinical development. In most cases, human gastrointestinal physiology is not properly considered, which leads to the application of inappropriate in vitro and animal models. Moreover, conditions in the stomach are often not fully understood. Important aspects such as the kinetics of fluid volumes, gastric pH or mechanical stresses have to be considered in a realistic manner, otherwise, the gastroretentive potential as well as drug release of novel formulations cannot be assessed correctly in preclinical studies. This review, therefore, highlights the most important aspects of human gastrointestinal physiology and discusses their potential implications for the evaluation of gastroretentive drug delivery systems.

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Stearic Acid-g-chitosan Polymeric Micelle for Oral Drug Delivery: In Vitro Transport and in Vivo Absorption

Molecular Pharmaceutics ◽

10.1021/mp100289v ◽

2010 ◽

Vol 8 (1) ◽

pp. 225-238 ◽

Cited By ~ 81

Author(s):

Hong Yuan ◽

Lin-Juan Lu ◽

Yong-Zhong Du ◽

Fu-Qiang Hu

Keyword(s):

Drug Delivery ◽

Stearic Acid ◽

Oral Drug Delivery ◽

Polymeric Micelle ◽

Oral Drug ◽

In Vivo Absorption

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In vitro and in vivo studies of enzyme-digestible hydrogels for oral drug delivery

Journal of Controlled Release ◽

10.1016/0168-3659(92)90071-x ◽

1992 ◽

Vol 19 (1-3) ◽

pp. 131-144 ◽

Cited By ~ 31

Author(s):

Waleed S.W. Shalaby ◽

William E. Blevins ◽

Kinam Park

Keyword(s):

Drug Delivery ◽

Oral Drug Delivery ◽

In Vivo Studies ◽

Oral Drug

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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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Determination of the in vitro and in vivo oral drug delivery capabilities of complexation hydrogels

10.17918/etd-1305 ◽

2021 ◽

Author(s):

Eric D. Perakslis

Keyword(s):

Drug Delivery ◽

Oral Drug Delivery ◽

Oral Drug

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Design of a Soft, Self-Uncoiling Stent for Extended Retention of Drug Delivery in the Small Intestine

2021 Design of Medical Devices Conference ◽

10.1115/dmd2021-1063 ◽

2020 ◽

Author(s):

Sunandita Sarker ◽

Ryan Jones ◽

Gabriel Chow ◽

Benjamin Terry

Keyword(s):

Drug Delivery ◽

Small Intestine ◽

Oral Drug Delivery ◽

Ileocecal Valve ◽

Drug Carriers ◽

Oral Formulation ◽

In Vivo Studies ◽

Oral Drug ◽

Biological Drugs

Abstract Despite being the preferred route of drug administration, the oral formulation of biological drugs is limited due to its intrinsic instability, low permeability, and physical, chemical and immunological barriers. Various innovative swallowable technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities. The current work presents a novel soft stent platform that can facilitate contact between the small intestine tissue and drug carriers to enhance drug absorption and increase residence time. This study aims to prove the concept of this novel platform and determine if the soft stent will retain orally to the ileocecal valve longer than a capsule-shaped bolus. Benchtop studies on an intestinal simulator showed successful retention of the soft stent compared to a control capsule. In vivo studies in pig models also showed that the soft stent was retained longer than the control capsule. Overall, this study shows promise that this novel platform could be used for oral drug delivery of biologics.

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Food Protein Based Core–Shell Nanocarriers for Oral Drug Delivery: Effect of Shell Composition on in Vitro and in Vivo Functional Performance of Zein Nanocarriers

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.6b01017 ◽

2017 ◽

Vol 14 (3) ◽

pp. 757-769 ◽

Cited By ~ 26

Author(s):

Mohammed S. Alqahtani ◽

M. Saiful Islam ◽

Satheesh Podaralla ◽

Radhey S. Kaushik ◽

Joshua Reineke ◽

...

Keyword(s):

Drug Delivery ◽

Oral Drug Delivery ◽

Functional Performance ◽

Oral Drug ◽

Core Shell ◽

Food Protein ◽

Shell Composition

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Bioadhesive Mannosylated Nanoparticles for Oral Drug Delivery

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.445 ◽

2006 ◽

Vol 6 (9) ◽

pp. 3203-3209 ◽

Cited By ~ 46

Author(s):

Hesham H. Salman ◽

Carlos Gamazo ◽

Miguel A. Campanero ◽

Juan M. Irache

Keyword(s):

Drug Delivery ◽

Oral Delivery ◽

Oral Drug Delivery ◽

Normal Mucosa ◽

Oral Drug ◽

Con A ◽

Distribution Profile ◽

The Given

The aim of this work was to design mannosylated Gantrez® AN nanoparticles (M-NP) and to describe their gut bioadhesive properties in order to develop a promising carrier for future applications in oral drug delivery. For that purpose, the process of the nanoparticles coating with mannosamine was optimized by the incubation of Gantrez® AN nanoparticles with different volumes of mannosamine aqueous solutions at different times. Then, the nanoparticles were characterized by measuring the size, zeta potential, mannosamine content, and concanavalin A (Con A) binding. Furthermore, in vivo quantitative bioadhesion study and kinetic analysis of the bioadhesion curves were performed after oral administration to rats of fluorescently labelled nanoparticles. The selected mannosylated nanoparticles (M-NP1 and M-NP10) were of homogenous sizes (about 300 and 200 nm), negatively charged and successfully coated with 36 and 18 μg mannosamine/mg NP, respectively. In vitro agglutination assay using Con A confirmed the successful coating of nanoparticles with mannosamine. The gut distribution profile of M-NP1 indicated a stronger bioadhesive capacity than M-NP10 and non-mannosylated ones, 1 h post-administration. Interestingly, M-NP1 showed an important ileum tropism where around 20% of the given dose remained adhered. Besides, the kinetic parameters of the bioadhesion profile of M-NP1 indicated their higher bioadhesive capacity with Qmax and AUCadh about 2-times higher than control ones. Moreover, fluorescence microscopy corroborated the stronger interactions of M-NP1 with the normal mucosa and demonstrated a strong uptake of these carriers by Peyer's patches. In conclusion, we propose that mannosylated nanoparticles could be a promising non-live vector for oral delivery strategies.

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