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Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs

หน่วยงาน จุฬาลงกรณ์มหาวิทยาลัย

รายละเอียด

ชื่อเรื่อง : Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs
นักวิจัย : Parkpoom Tengamnuay , Achariya Sailasuta , Garnpimol C. Ritthidej
คำค้น : Chitosan , Peptide drugs
หน่วยงาน : จุฬาลงกรณ์มหาวิทยาลัย
ผู้ร่วมงาน : Chulalongkorn University. Faculty of Pharmacy , Chulalongkorn University. Faculty of Veterinary , Chulalongkorn University. Faculty of Pharmacy
ปีพิมพ์ : 2541
อ้างอิง : http://cuir.car.chula.ac.th/handle/123456789/2178
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : -
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Objective: To evaluate the safety and efficacy of chitosan (CS) as nasal absorption enhances of peptides. Methods: Two types of chitosans, i.e. CS J (free amine chitosan) and CD G (water-soluble glutamate salt), were evaluate for their masal absorption enhancing effectd on L-Tyr-D-Arg([D-Arg[square]]-Kyotorphic), an enzymatically stable dipeptide, using an in situ rat nasal perfusion technique. The two chitosans were subsequently studies for their possible membrane damaging effects based on measurements of releases mucosal components and histological evaluation. Results: At 0.5% w/v, both CS J and CS G were effects in enhancing the nasal absorption of [D-Arg[square]]-Kyotorphin, The enhancing effect of CS J was significantly greater at pH 4.0 than at pH 5.0 and 6.0 (p<0.05) in accordance with the nature of the free amine chitosan to swell and dissolve better in the more acidic conditions. However, there were no significant differences in the adjuvantactivity of the soluble acid salt CS G at pH 4.0, 5.0 and 6.0 (p>0.05). CS J and G were subsequently selected for further studies at their optimum pH (4.0 for CS J and 6.0 for CS G). At only 0.02% w/v, their enhancing effects were already significant and similar to that of 5% w/v hydroxypropyl-beta-cyclodextrin (HP-beta-CD). Determination of the protein and phosphorus content in the nasal perfusates indicated that the two chitosans, at 0.1% w/v, caused minimal release of these substances similae to that of HP-beta-CD (p>0.05). However, they were much smaller than the previously reported values for dimethy-beta-cyclodextrin, an effective enhancer which, at 5% w/v, gave the protein values phoshorus release rates about 4-7 folds higher than chitisans. Morphological evaluation of the rat nasal mucosa following daily administration of 1% w/v CS J and G and 5% w/v HP-beta-CD for 14 days indicated that the three enhanced produced only mild to moderate irritation, the most common signs being mucus hypersecretion andgoblet cell distention. The effects of the two chitosans on the rat nasal epithelial integrity were also reversible as judged from the reduction in the extent of lactate dehydrogenase release, a cytosolic enzyme maker, following removal of chitosans from the nasal mucosa. Conclusions: Both CS J and CS G were effective in enhancing nasal absorption of [D-Arg[square]]-Kytotorphin. Results from the mucosal compenent release, morphological and reversibility studies indicated that chitosans may have a potential for further studies as a safe and effective nasal absorption enhancer.

บรรณานุกรม :
Parkpoom Tengamnuay , Achariya Sailasuta , Garnpimol C. Ritthidej . (2541). Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs.
    กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย.
Parkpoom Tengamnuay , Achariya Sailasuta , Garnpimol C. Ritthidej . 2541. "Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs".
    กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย.
Parkpoom Tengamnuay , Achariya Sailasuta , Garnpimol C. Ritthidej . "Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs."
    กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย, 2541. Print.
Parkpoom Tengamnuay , Achariya Sailasuta , Garnpimol C. Ritthidej . Efficacy and mechanistic studies of chitosan as nasal absorption enhancer of peptide drugs. กรุงเทพมหานคร : จุฬาลงกรณ์มหาวิทยาลัย; 2541.