Effectiveness of submicronized chitosan-coated liposomes in oral absorption of indomethacin

Sugihara, Hikaru; Yamamoto, Hiromitsu; Kawashima, Yasunaru; Takeuchi, Hirofumi

doi:10.3109/08982104.2011.621128

Cited by 41 publications

(18 citation statements)

References 16 publications

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“…9) In the present study, therefore, we also investigated the effect of feeding on the time dependency of the gastrointestinal transition of ssCS-Lip. The liposomal distributions following the oral administration of ssCS-Lip in the fasting and fed conditions are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Effects of Food Intake on the Mucoadhesive and Gastroretentive Properties of Submicron-Sized Chitosan-Coated Liposomes

Sugihara

Yamamoto

Kawashima

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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The gastrointestinal transition of mucoadhesive drug carriers may be affected by food intake, since food changes the physiological conditions of the gastrointestinal tract, and the food content itself is a physical obstruction for the drug carriers. Here we investigated the effects of food intake on the gastrointestinal transition and mucoadhesive function of submicron-sized chitosan-coated liposomes (ssCS-Lip). The stomach and small intestine were removed after oral administration of ssCS-Lip and non-coated liposomes (ssLip) containing fluorescent dye to fasted or fed rats, and retentive properties were quantitatively confirmed by measuring the amount of dye in each part of the gastrointestinal tract. Both types of liposome were retained in the stomach at approx. 40% in the fed rats at 1 h after oral administration, whereas transitions in the intestine were reduced compared to the fasted rats. However, the transition of ssCS-Lip in intestine was prolonged compared to ssLip even, in the fed state. The mucoadhesive behavior of ssCS-Lip was evaluated by confocal laser scanning microscopy. The ssCS-Lip tended to penetrate into the mucosal part of the intestine, and in addition, ssCS-Lip was detected in the basolateral side in both conditions, and therefore the mucopenetrative function was confirmed in the fed condition. Based on these results, we confirmed that ssCS-Lip shows a predominant gastrointestinal transition and mucopenetration, even after food intake.Key words liposome; chitosan; mucoadhesion; food intake; oral A drug delivered in a mucoadhesive dosage form adheres to mucosa in the gastrointestinal tract. The mucoadhesive dosage form improves the absorption of poorly absorbed compounds based on its extended retention time at absorption sites.Liposomes are phospholipid vesicles, comprising a phospholipid bilayer surrounding an aqueous compartment. Due to their biphasic characteristic and diversity in design, liposomes offer an adaptable function for improving drug absorption. We developed mucoadhesive liposomes by coating the anionic liposomal surface with a cationic mucoadhesive polymer, chitosan. The effectiveness of the chitosan-coated liposomes (CS-Lip) was confirmed in previous studies that showed enhanced and prolonged pharmacological effects of insulin, which was orally administered to rats in the polymercoated liposomal form.1,2) The effectiveness of mucoadhesive liposomes in drug absorption has also been demonstrated by using calcitonin as a model peptide drug. Carbopol-coated liposomes, with a mucoadhesive property similar to that of CS-Lip, were as effective as CS-Lip.3) In addition, the effects of particle size on the mucoadhesive properties of chitosan-coated liposomes and on the absorption of entrapped calcitonin were evaluated. Submicron-sized chitosan-coated liposomes (ssCS-Lip) showed excellent penetration into the intestinal mucosa, and the pharmacological effect of calcitonin was prolonged up to 120 h after oral administration to rats. 4)The influence of food on gastrointestinal conditio...

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Section: Resultsmentioning

confidence: 99%

Effects of Food Intake on the Mucoadhesive and Gastroretentive Properties of Submicron-Sized Chitosan-Coated Liposomes

Sugihara

Yamamoto

Kawashima

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Importantly, many works report the use of chitosan as a coating material, instead of being a part of the matrix of the system [22,26,27,28], which is a relevant recognition of chitosan appealing properties. In this respect, the coating of several different core structures has been reported, including solid lipid nanoparticles [26,29], polymeric nano and microparticles [28,30,31,32] and liposomes [33,34]. The clear objective of such an approach is to modify the surface properties of the core structure, either to improve the pattern of interaction with surrounding structures or to improve the biodegradation profile.…”

Section: Chitosan Application In Drug Deliverymentioning

confidence: 99%

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

Rodrigues

Dionísio

López

et al. 2012

JFB

295

154

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Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.

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“…Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that belongs to BCS class II drug. Sugihara et al tried to improve the oral BA of indomethacin by using liposomes modified with mucoadhesive polymer, chitosan [24]. They also controlled the particle size of chitosan-coated liposomes to fall within the submicron range (270-310 nm).…”

Section: Indomethacinmentioning

confidence: 99%

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

Lee

2020

Pharmaceutics

179

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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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Effectiveness of submicronized chitosan-coated liposomes in oral absorption of indomethacin

Cited by 41 publications

References 16 publications

Effects of Food Intake on the Mucoadhesive and Gastroretentive Properties of Submicron-Sized Chitosan-Coated Liposomes

Effects of Food Intake on the Mucoadhesive and Gastroretentive Properties of Submicron-Sized Chitosan-Coated Liposomes

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

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

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