In vitro evaluation and modification of pectinate gel beads containing trimethyl chitosan, as a multi-particulate system for delivery of water-soluble macromolecules to colon

Atyabi, Fatemeh; Majzoob, Sayeh; Iman, Maryam; Salehi, Masoud; Dorkoosh, Farid Abedin

doi:10.1016/j.carbpol.2005.02.005

Cited by 88 publications

(47 citation statements)

References 29 publications

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“…Conversely, the ZPG beads did not disintegrate and only a small amount of MSKE (5%-15%) was released after 8 h of incubation. These results are consistent with those of El-Gibaly [18], Atyabi et al [19] and Chambin et al [20] who reported differences in the degree of cross-linking with the two pectinate gel types and that the CPG beads displayed more drastic swelling-erosion in the intestinal medium than the ZPG beads. Calcium ions could possibly form loose linkages with carboxyl groups in the pectin chains, allowing the penetration of SIM into the Ca-pectinate network.…”

Section: In Vitro Release Studies Of Mske-loaded Pectinate Beadssupporting

confidence: 82%

The Development, Physicochemical Characterisation and in Vitro Drug Release Studies of Pectinate Gel Beads Containing Thai Mango Seed Kernel Extract

et al. 2013

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Pectinate gel beads containing Thai mango seed kernel extract (MSKE, cultivar 'Fahlun') were developed and characterised for the purpose of colon-targeted delivery. The MSKE-loaded pectinate beads were prepared using ionotropic gelation with varying pectin-to-MSKE ratios, MSKE concentrations, and concentrations of two cross-linkers (calcium chloride and zinc acetate). The formulated beads were spherical in shape and ranged in size between 1.13 mm and 1.88 mm. Zinc-pectinate (ZPG) beads containing high amounts of MSKE showed complete entrapment efficiency (EE) of MSKE (100%), while calcium-pectinate (CPG) beads demonstrated 70% EE. The in vitro release tests indicated that MSKE-loaded CPG beads were unstable in both simulated gastric medium (SGM) and simulated intestinal medium (SIM), while MSKE-loaded ZPG beads were stable in SIM but unable to prevent the release of MSKE in SGM. The protection of ZPG beads with gastro-resistant capsules (Eudragit ® L 100-55) resulted in stability in both SGM and SIM; they disintegrated immediately in simulated colonic medium containing pectinolytic enzymes. MSKE-loaded ZPG beads were stable at 4, 25 and 45 °C during the study period OPEN ACCESSMolecules 2013, 18 6505 of four months. The present study revealed that ZPG beads in enteric-coated capsules might be a promising carrier for delivering MSKE to the colon.

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Section: In Vitro Release Studies Of Mske-loaded Pectinate Beadssupporting

confidence: 82%

The Development, Physicochemical Characterisation and in Vitro Drug Release Studies of Pectinate Gel Beads Containing Thai Mango Seed Kernel Extract

et al. 2013

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“…High methoxyl pectin has been advocated as the polymer of choice because it is inherently less water soluble than low methoxyl pectin (75,76,86). However, it is reported that low methoxyl pectinate beads coated with high methoxyl pectin exhibit a higher propensity of drug release than uncoated beads (92). This is ascribed to prolonged exposure of drug core to moist high methoxyl pectin layer during coating process.…”

Section: -Fluorouracilmentioning

confidence: 99%

“…Enzymatic degradation of pectin components forms the primary mechanism of colon-specific drug release. Nevertheless, the leaching of pectin components from coat may suppress the formation of hydrated pectin channels (87,92). The undigested coat on matrix can be reconstructed via distension, plugging up pores, reducing free volume between polymer chains and preventing drug release.…”

Section: -Fluorouracilmentioning

confidence: 99%

Pectin Matrix as Oral Drug Delivery Vehicle for Colon Cancer Treatment

2010

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Abstract. Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.

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“…13,18) On the other hand, phosphate solution provided a buffer environment with a certain pH around isoelectric point of insulin, which also contributed to a better entrapment capability.…”

Section: Morphology Of Cpg Microbeads Typical Scanning Electron Micromentioning

confidence: 99%

“…The main drawback of calcium pectinate gel (CPG) beads is their macroporous structures, which may cause low entrapment efficiency 4,9) and fast release [9][10][11] of incorporated drugs, especially for those of low molecular weight and water-solubility. In recent investigation, emulsion-gelation method 12) or a multi-particulate system 13) could also exhibit a high drug entrapment efficiency and a slow release profile. However, to some proteins, this method does not work since the proteins have to be exposed to organic solvent systems which lead to denaturation.…”

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confidence: 99%

Calcium Pectinate Gel Bead Intended for Oral Protein Delivery: Preparation Improvement and Formulation Development

Zhao

Huang

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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663With recent advances in biotechnology, protein and peptide drugs have become a focus on current formulation research. Most of protein pharmaceuticals are mostly administered parenterally, 1) with the limitations included that oscillating blood drug concentrations caused by repeated doses and patient compliance resulted from frequent injections. 2)Oral delivery, which allows for a more varied load to be released, is the most convenient method of administration. However, it still remains a challenge especially since the labile structures of proteins are prone to hydrolization and enzymatic degradation.3) Natural hydrogel systems, especially polysaccharides such as pectin and chitosan, have been researched extensively in the development of protein and peptide drugs delivery systems in recent years. 2,[4][5][6] Pectin is an anionic, soluble heterogeneous polysaccharide containing linear chains of a-(1→4)-D-galacturonic acid residues. 7,8) Low-methoxy pectin with degree of esterification less than 50% can form rigid gels by the action of calcium ions or multivalent cations and cross-link the galacturonic acid chains. The main drawback of calcium pectinate gel (CPG) beads is their macroporous structures, which may cause low entrapment efficiency 4,9) and fast release 9-11) of incorporated drugs, especially for those of low molecular weight and water-solubility. In recent investigation, emulsion-gelation method 12) or a multi-particulate system 13) could also exhibit a high drug entrapment efficiency and a slow release profile. However, to some proteins, this method does not work since the proteins have to be exposed to organic solvent systems which lead to denaturation. Therefore, it is of great importance to develop a method capable to increase drug entrapment efficiencies and stable for protein and peptide drugs loaded.Isoelectric point is of great significance in protein properties because it is the pH at which proteins have minimal solubility and most stable property against denaturation.14-16) We hypothesized that minimization of the protein dissolution and diffusion during their preparation by maintaining the pH of all working solutions at or close to its isoelectric point could enhance the entrapment efficiency of the microbeads. It was of interest to see whether microbeads containing proteins such as insulin could be prepared by this strategy and exhibited better profiles.In this study, the CPG microbeads were prepared by ionotropic gelation technique coupled with working solution pH design for potential use of oral delivery system of protein and peptide drugs. Insulin, one of the most important drugs for diabetes, was chosen as a model amphoteric protein due to its comparative stability and crystallizing under different conditions. In addition, an air compressor was employed to reduce the particle size. This work also focused on the influences of some factors, such as phosphate buffer concentration, pH value of CaCl 2 solution, calcium concentration and pectin concentration, on the CPG microbeads propertie...

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In vitro evaluation and modification of pectinate gel beads containing trimethyl chitosan, as a multi-particulate system for delivery of water-soluble macromolecules to colon

Cited by 88 publications

References 29 publications

The Development, Physicochemical Characterisation and in Vitro Drug Release Studies of Pectinate Gel Beads Containing Thai Mango Seed Kernel Extract

The Development, Physicochemical Characterisation and in Vitro Drug Release Studies of Pectinate Gel Beads Containing Thai Mango Seed Kernel Extract

Pectin Matrix as Oral Drug Delivery Vehicle for Colon Cancer Treatment

Calcium Pectinate Gel Bead Intended for Oral Protein Delivery: Preparation Improvement and Formulation Development

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