The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study

Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps® HPMC capsules, Vcaps® Plus HPMC capsules, gelatin and DRcaps® designed release capsules were used. The three HPMC-based capsules (Vcaps®, Vcaps® Plus and DRcaps® capsules) were tested as single capsules; furthermore, seven DUOCAP® capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and 13C3) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP® capsule-in-capsule configuration using a DRcaps® designed release capsule within a DRcaps® designed release outer capsule. In this combination, the inner DRcaps® designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps® Plus HPMC capsules showed the fastest and most consistent disintegration.

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Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation

Vaccines ◽

10.3390/vaccines9040369 ◽

2021 ◽

Vol 9 (4) ◽

pp. 369

Author(s):

Jennifer Schwestka ◽

Eva Stoger

Keyword(s):

Targeted Delivery ◽

Oral Delivery ◽

Protective Coatings ◽

Production Costs ◽

Cell Wall Proteins ◽

Production Host ◽

And Storage ◽

Harsh Conditions ◽

Encapsulation Methods

The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, such as the formulation of tablets for oral delivery, others require complex procedures that add significantly to production costs and require low-temperature transport and storage, making them inaccessible in developing countries. In this review we consider the benefits of encapsulation technologies based on plants. Plant-derived biopolymers such as starch and the maize storage protein zein are already used as protective coatings, but plant cells used as production host provide natural in vivo bioencapsulation that survives passage through the stomach and releases drugs in the intestine, due to the presence of microbes that can digest the cell wall. Proteins can also be encapsulated in subcellular compartments such as protein bodies, which ensure stability and activity while often conferring additional immunomodulatory effects. Finally, we consider the incorporation of drugs and vaccines into plant-derived nanoparticles assembled from the components of viruses. These are extremely versatile, allowing the display of epitopes and targeting peptides as well as carrying cargoes of drugs and imaging molecules.

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Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study

Scientific Reports ◽

10.1038/s41598-019-53999-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 6

Author(s):

Armin Mooranian ◽

Susbin Raj Wagle ◽

Bozica Kovacevic ◽

Ryu Takechi ◽

John Mamo ◽

...

Keyword(s):

Bile Acid ◽

Targeted Delivery ◽

Oral Delivery ◽

Ex Vivo ◽

Biological Effects ◽

Protective Effects ◽

Β Cells ◽

Positive Effects ◽

Anti Inflammatory

AbstractThe antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells. PB has poor solubility and bioavailability, and despite attempts to improve its oral delivery, none has shown dramatic improvements in absorption or antidiabetic effects. Preliminary data has shown potential benefits from bile acid co-encapsulation with PB. One bile acid has shown best potential improvement of PB oral delivery (ursodeoxycholic acid, UDCA). This study aimed to examine PB and UDCA microcapsules (with UDCA microcapsules serving as control) in terms of the microcapsules’ morphology, biological effects ex vivo, and their hypoglycemic and antilipidemic and anti-inflammatory effects in vivo. PBUDCA and UDCA microcapsules were examined in vitro (formulation studies), ex vivo and in vivo. PBUDCA microcapsules exerted positive effects on β-cells viability at hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on the prediabetic mice. In conclusion, PBUDCA co-encapsulation have showed beneficial therapeutic impact of dual antioxidant-bile acid effects in diabetes treatment.

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Preparation andIn VitroRelease of Drug-Loaded Microparticles for Oral Delivery Using Wholegrain Sorghum Kafirin Protein

International Journal of Polymer Science ◽

10.1155/2015/343647 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Esther T. L. Lau ◽

Stuart K. Johnson ◽

Roger A. Stanley ◽

Deirdre Mikkelsen ◽

Zhongxiang Fang ◽

...

Keyword(s):

Drug Delivery ◽

Gastrointestinal Tract ◽

Drug Delivery System ◽

Delivery System ◽

Targeted Delivery ◽

Oral Delivery ◽

Protein Digestibility ◽

Target Area ◽

Sorghum Grains

Kafirin microparticles have been proposed as an oral nutraceutical and drug delivery system. This study investigates microparticles formed with kafirin extracted from white and raw versus cooked red sorghum grains as an oral delivery system. Targeted delivery to the colon would be beneficial for medication such as prednisolone, which is used in the management of inflammatory bowel disease. Therefore, prednisolone was loaded into microparticles of kafirin from the different sources using phase separation. Differences were observed in the protein content,in vitroprotein digestibility, and protein electrophoretic profile of the various sources of sorghum grains, kafirin extracts, and kafirin microparticles. For all of the formulations, the majority of the loaded prednisolone was not released inin vitroconditions simulating the upper gastrointestinal tract, indicating that most of the encapsulated drug could reach the target area of the lower gastrointestinal tract. This suggests that these kafirin microparticles may have potential as a colon-targeted nutraceutical and drug delivery system.

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ORAL DELIVERY OF SILVER NANOPARTICLES – A REVIEW

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i11.42986 ◽

2021 ◽

pp. 9-14

Author(s):

VEDAMURTHY JOSHI ◽

FIRDOS SULTHANA ◽

DINESHA RAMADAS

Keyword(s):

Silver Nanoparticles ◽

Gastrointestinal Tract ◽

Adverse Effects ◽

Drug Absorption ◽

Oral Delivery ◽

English Language ◽

In Vivo Studies ◽

Recent Trends

Silver nanoparticles (NP) offer many applications in the science and technology. Oral delivery of such tiny particles results in enhanced drug absorption, reduction in dose, and minimize adverse effects. This review focuses on the mainly on the effects in the gastrointestinal tract along with its in vitro and in vivo studies carried on the silver NP. In this review, we compiled some of the extensive research in the field of silver NP, highlighting some of the most recent trends in the area. Search was carried in English language using Science direct, PubMed, and Google scholar search engines. The effects of silver NP on gastrointestinal tract such as absorption, distribution, metabolism, and elimination were compiled in this review. In addition, selected in vitro and in vivo studies related to the same are discussed. The accumulation of silver NP leading to Arginia condition also emphasized in the study. Silver NP and herbal silver NP in oral delivery can be exploited for the further safer and effective treatment.

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Development of a Novel Oral Delivery Vehicle for Probiotics

Current Pharmaceutical Design ◽

10.2174/1381612826666200210111925 ◽

2020 ◽

Vol 26 (26) ◽

pp. 3134-3140 ◽

Cited By ~ 1

Author(s):

Kevin Enck ◽

Surya Banks ◽

Hariom Yadav ◽

Mark E. Welker ◽

Emmanuel C. Opara

Keyword(s):

Targeted Delivery ◽

Oral Delivery ◽

Oral Drug Delivery ◽

Oral Drug ◽

Bacterial Cells ◽

Alginate Hydrogel ◽

Chemically Modified ◽

Delivery Platform ◽

Ph Conditions

Background: There is a significant interest in effective oral drug delivery of therapeutic substances. For probiotics, there is a particular need for a delivery platform that protects the bacteria from destruction by the acidic stomach while enabling targeted delivery to the intestine where microbiota naturally reside. The use of probiotics and how they impact the gut microbiota is a growing field and holds promise for the treatment of a variety of gastrointestinal diseases, including irritable bowel disease Crohn’s disease and C. diff and other diseases, such as obesity, diabetes, Parkinson’s, and Alzheimer’s diseases. Objective: The aim of this research was to use our newly developed chemically-modified alginate hydrogel with the characteristic feature of stability in acidic environments but disintegration under neutral-basic pH conditions to design a novel system for effective targeted delivery of ingested probiotics. Method and Results: We have used the approach of encapsulation of bacterial cells in the hydrogel of the modified alginate with in vitro studies in both simulated stomach acid and intestinal fluid conditions to demonstrate the potential application of this novel platform in oral delivery of probiotics. Our data provide a proof-of-concept that enables further studies in vivo with this delivery platform. Conclusion: We have demonstrated in the present study that our chemically modified alginate hydrogel is resistant to acidic conditions and protects bacterial cells encapsulated in it, but it is sensitive to neutral-basic pH conditions under which it disintegrates and releases its viable bacteria cell payload. Our data provide a proof-ofconcept that enables further studies in vivo with this delivery platform for the efficacy of therapeutic bacteria in various disease conditions.

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Medical Applications of Magnetic Nanoparticles

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.464 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2762-2768 ◽

Cited By ~ 75

Author(s):

C. Alexiou ◽

R. Jurgons ◽

C. Seliger ◽

H. Iro

Keyword(s):

Magnetic Nanoparticles ◽

Targeted Delivery ◽

Cell Separation ◽

Medical Applications ◽

Resonance Imaging ◽

Promising Tool ◽

Magnetic Cell Separation ◽

Magnetic Resonance Imaging Mri

In recent years biomedical research indicated, that magnetic nanoparticles can be a promising tool for several applications in vitro and in vivo. In medicine many approaches were investigated for diagnosis and therapy and offered a great variety of applications. Magnetic cell separation, magnetic resonance imaging (MRI), magnetic targeted delivery of therapeutics or magnetically induced hyperthermia are approaches of particular clinical relevance. For medical use, especially for in vivo application it is of great importance that these particles do not have any toxic effects or incompatibility with biological organism. Investigations on applicable particles induced a variability of micro- and nanostructures with different materials, sizes, and specific surface chemistry.

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Topical application of solubilized Reseda luteola extract inhibits ultraviolet B-induced inflammation in human volunteers in vivo

Planta Medica ◽

10.1055/s-0029-1234772 ◽

2009 ◽

Vol 75 (09) ◽

Author(s):

F Casetti ◽

W Jung ◽

U Wölfle ◽

J Reuter ◽

K Neumann ◽

...

Keyword(s):

Topical Application ◽

Ultraviolet B ◽

Human Volunteers

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A Multicenter Study of Recombinant Factor VIII (RecombinateTM) in Previously Treated Patients with Hemophilia A

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656030 ◽

1997 ◽

Vol 77 (04) ◽

pp. 660-667 ◽

Cited By ~ 110

Author(s):

G C White ◽

S Courter ◽

G L Bray ◽

M Lee ◽

E D Gomperts ◽

...

Keyword(s):

Hemophilia A ◽

Recombinant Dna ◽

Home Treatment ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Studies ◽

Open Label ◽

Treat Ment ◽

Previously Treated Patients ◽

Bleeding Episodes

SummaryA prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treat- ment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII; none was serious. No patient developed an inhibitor to r FVIII.

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