Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals

Homayun, Bahman; Lin, Xueting; Choi, Hyo-Jick

doi:10.3390/pharmaceutics11030129

Cited by 602 publications

(424 citation statements)

References 220 publications

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“…Specifically, rats are one of the most widely used small animal models for the assessment of new pharmaceutical entities during pre-clinical studies [3][4][5][6][7][8][9]. The oral route is the most preferred and convenient way to administer drugs which can either be formulated to act locally in the gastrointestinal (GI) tract or be absorbed to achieve a systemic effect [10]. Hard shell capsules are commonly used for oral administration of drugs.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

Gómez-Lado

Seoane-Viaño

Matiz³

et al. 2020

Pharmaceutics

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Following oral administration, gastric emptying is often a rate-limiting step in the absorption of drugs and is dependent on both physiological and pharmaceutical factors. To guide translation into humans, small animal imaging during pre-clinical studies has been increasingly used to localise the gastrointestinal transit of solid dosage forms. In contrast to humans, however, anaesthesia is usually required for effective imaging in animals which may have unintended effects on intestinal physiology. This study evaluated the effect of anaesthesia and capsule size on the gastric emptying rate of coated capsules in rats. Computed tomography (CT) imaging was used to track and locate the capsules through the gastrointestinal tract. Two commercial gelatine mini-capsules (size 9 and 9h) were filled with barium sulphate (contrast agent) and coated using Eudragit L. Under the effect of anaesthesia, none of the capsules emptied from the stomach. In non-anaesthetised rats, most of the size 9 capsules did not empty from the stomach, whereas the majority of the smaller size 9h capsules successfully emptied from the stomach and moved into the intestine. This study demonstrates that even with capsules designed to empty from the stomach in rats, the gastric emptying of such solid oral dosage forms is not guaranteed. In addition, the use of anaesthesia was found to abolish gastric emptying of both capsule sizes. The work herein further highlights the utility of CT imaging for the effective visualisation and location of solid dosage forms in the intestinal tract of rats without the use of anaesthesia.

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Section: Introductionmentioning

confidence: 99%

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

Gómez-Lado

Seoane-Viaño

Matiz³

et al. 2020

Pharmaceutics

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“…ELISA analysis shows that insulin released from the gel is recovered quantitatively, while in the absence of gel is completely hydrolyzed. Therefore, the described hydrogelators show successful results in the proof of concept experiment of protection and release of insulin, overcoming the primary barrier for oral administration of drugs, the harsh conditions of pH and presence of hydrolytic enzymes along the gastrointestinal tract …”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the described hydrogelators show successful results in the proof of concept experiment of protection and release of insulin, overcoming the primary barrier for oral administration of drugs, the harsh conditions of pH and presence of hydrolytic enzymes along the gastrointestinal tract. [62] Overall, relatively simple molecules, which can be prepared quickly on grams scale, form hydrogels that show dual stimuli responsiveness. The modular nature of their skeleton paves the way for improved properties based on different amino acid building blocks and terminal units.…”

Section: Resultsmentioning

confidence: 99%

A Dual Stimuli Responsive Supramolecular Gel Provides Insulin Hydrolysis Protection and Redox‐Controlled Release of Actives

Navarro‐Barreda

Bedrina

Galindo

et al. 2020

Macro Chemistry & Physics

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Two supramolecular hydrogelators containing a central disulfide moiety and terminal carboxylic acid groups are studied. On the one hand, the hydrogels are responsive to a reductive environment, which transforms the disulfide unit to the corresponding thiols. On the other hand, the hydrogels show pH response associated with the presence of carboxylic acid units. Gels are formed at pH below ≈4 while at higher pH values, ionization of the gelators provokes gel disassembly. The properties of the gel are exploited for the release, as a proof of concept, of Bromophenol Blue in the presence of the reducing species tris(2‐carboxyethyl)phosphine hydrochloride. Additionally, insulin is loaded into the hydrogels and protected from hydrolysis with simulated gastric fluid containing pepsin. Quantitative release of unaltered insulin, checked with an enzyme‐linked immunosorbent assay colorimetric assay, is observed upon treatment with pH 7.4 buffer. This behavior would permit the use of the new hydrogels for oral insulin delivery.

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“…The greatest advantage of liposomes as a drug delivery system may be their excellent biocompatibility, which has already been proven by the approved liposomal formulations for intravenous administration, such as Doxil ® , a doxorubicin-containing stealth liposome. As mentioned above, liposomes can encapsulate various drugs, including hydrophilic and hydrophobic drugs, as well as peptides, proteins, and nucleic acids, without loss of activity [48]. There is a large variety of available phospholipids and other lipids providing enormous flexibility of formulations.…”

Section: Advantages and Disadvantages Of Liposomes For Oral Deliverymentioning

confidence: 99%

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

Lee

2020

Pharmaceutics

178

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It has been known that a considerable number of drugs in clinical use or under development are water-insoluble drugs with poor bioavailability (BA). The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase dissolution and subsequently absorption in the gastrointestinal (GI) tract because of its biocompatibility and ability to encapsulate hydrophobic molecules in the lipid domain. However, there have been several drawbacks, such as structural instability in the GI tract and poor permeability across intestinal epithelia because of its relatively large size. In addition, there have been no liposomal formulations approved for oral use to date, despite the success of parenteral liposomes. Nevertheless, liposomal oral delivery has resurged with the rapid increase of published studies in the last decade. However, it is discouraging that most of this research has been in vitro studies only and there have not been many water-insoluble drugs with in vivo data. The present review focused on the in vivo evidence for the improved BA of water-insoluble drugs using liposomes to resolve doubts raised concerning liposomal oral delivery and attempted to provide insight by highlighting the approaches used for in vivo achievements.Pharmaceutics 2020, 12, 264 2 of 30 However, there have been several drawbacks to be overcome, such as instability in the GI tract and poor permeability across the intestinal epithelia because of liposomes' relatively large size [8]. Moreover, it seemed that liposomal oral delivery was faltering during 1980s due to some disappointing results for insulin [9]. However, liposomal oral delivery resurged with a rapid increase in the number of papers published, as shown in Pubmed search results, mainly due to various advanced modification technologies, even though liposomal oral delivery-related papers account for only 5-6% of the total number of liposomes-related studies (Figure 1). In addition, there was an encouraging meta-analysis report in which phospholipid-based solid formulations were analyzed as being effective for BA enhancement [10]. Although liposomal delivery does not seem to achieve satisfactory improvement of oral BA for peptides and protein drugs yet, it looks more promising for oral delivery of hydrophobic drugs because liposomes can solubilize poorly water-soluble drugs, protect the drug from degradation in the GI tract and enhance permeability through the epithelial cell membrane, consequently increasing oral BA. However, most published papers performed in vitro studies only, thus lacking in vivo pharmacokinetic results. The present review focuses on the in vivo evidence for the improved BA of water-insoluble drugs and highlights the approaches used for in vivo achievements.

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Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals

Cited by 602 publications

References 220 publications

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

A Dual Stimuli Responsive Supramolecular Gel Provides Insulin Hydrolysis Protection and Redox‐Controlled Release of Actives

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

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