Author(s): Chalasani KB, Russell-Jones GJ, Jain AK, Diwan PV, Jain SK
The potential utility of vitamin B12 carrier system for the oral delivery of conjugated peptides/proteins and enhancement of nanoparticles (NPs) transport has been demonstrated. The present study aims to optimize the effectiveness of VB12-NPs conjugates using different levels of cross-linking, linked with different VB(12)-coatings and evaluates in animal models to investigate an efficient insulin carrier. Amino alkyl VB12 derivatives suitable for oral delivery were synthesized at 5'hydoxy ribose and e-propionamide sites via carbamate and ester/amide linkages, and were coupled to succinic acid modified dextran NPs of varied cross-linking. VB12 binding was confirmed by XPS analysis, and was quantified by HPLC (4.0 to 5.7% w/w of NPs). These polydisperse NPs conjugates showed higher size, high insulin entrapment and faster insulin release with low levels of cross-linking. These VB12-NPs conjugates (150-300 nm) showed profound (70-75% blood glucose reductions) and prolonged (54 h) anti-diabetic effects with biphasic behaviour in STZ diabetic rats. NPs with the low levels of cross-linking were found to be superior carriers, and were more effective with VB12 derivatives of carbamate linkage. The pharmacological availability relative to SC insulin was found to be 29.4%, which was superior compared to NPs conjugate of ester linked VB12 (1.5 fold) and relatively higher cross-linked particles (1.1 fold). Further, the NPs carrier demonstrated a similar oral insulin efficacy in congenital diabetic mice (60% reduction at 20 h). Significant quantities of plasma insulin were found in both animal models (231 and 197 muIU/ml). At two investigated doses, the carrier system shows dose response. Pre-dosing with a large excess of free VB12 minimized the observed activity, indicating predominance of VB12 mediated uptake. It is concluded that VB12-dextran NPs conjugate is a viable carrier for peroral insulin delivery to treat diabetics.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/17707540
Author(s): Beals J, Brader M, De Felippis M, Kovach P
Author(s): American Diabetes Association
Author(s): Fonte P, Araújo F, Reis S, Sarmento B
Author(s): Rosenfeld L
Author(s): Al-Tabakha MM, Arida AL
Author(s): Bhatia E, Aggarwal A
Author(s): Chaturvedi K, Ganguly K, Nadagouda MN, Aminabhavi TM
Author(s): Magwire ML
Author(s): Arbit E, Kidron M
Author(s): Varshosaz J
Author(s): Heinemann L, Jacques Y
Author(s): Eldor R, Arbit E, Schurr D, Kidron M, Hersko A
Author(s): Gu Z, Aimetti AA, Wang Q, Dang TT, Zhang Y, et al.
Author(s): Trapani A, Lopedota A, Franco M, Cioffi N, Ieva E, et al.
Author(s): Cui F, Qian F, Zhao Z, Yin L, Tang C, et al.
Author(s): Li T, Shi XW, Du YM, Tang YF
Author(s): Pan Y, Li YJ, Zhao HY, Zheng JM, Xu H, et al.
Author(s): Ma Z, Yeoh HH, Lim LY
Author(s): Zhang N, Ping Q, Huang G, Xu W, Cheng Y, et al.
Author(s): Chen MC, Sonaje K, Chen KJ, Sung HW
Author(s): Babu VR, Patel P, Mundargi RC, Rangaswamy V, Aminabhavi TM
Author(s): Damgé C, Reis CP, Maincent P
Author(s): des Rieux A, Fievez V, Garinot M, Schneider YJ, Préat V
Author(s): Michel C, Aprahamian M, Defontaine L, Couvreur P, Damgé C
Author(s): Damgé C, Michel C, Aprahamian M, Couvreur P
Author(s): Sajeesh S, Sharma CP
Author(s): Carino GP, Jacob JS, Mathiowitz E
Author(s): Jose S, Fangueiro JF, Smitha J, Cinu TA, Chacko AJ, et al.
Author(s): Chaudhury A, Das S
Author(s): Niu M, Lua Y, Hovgaard L, Guan P, Tan Y, et al.
Author(s): Xiong XY, Li YP, Li ZL, Zhou CL, Tam KC, et al.
Author(s): Sarmento B, Martins S, Ferreira D, Souto EB
Author(s): Elsayed AM
Author(s): Sung HW, Sonaje K, Feng SS
Author(s): Severino P, Andreani T, Macedo AS, Fangueiro JF, Santana MH, et al.
Author(s): Ramachandran R, Paul W, Sharma CP
Author(s): Mundargi RC, Rangaswamy V, Aminabhavi TM
Author(s): Mundargi RC, Rangaswamy V, Aminabhavi TM
Author(s): Najafzadeh H, Kooshapur H, Kianidehkordi F
Author(s): Sung HW, Sonaje K, Liao ZX, Hsu LW, Chuang EY
Author(s): Pridgen EM, Alexis F, Kuo TT, Levy-Nissenbaum E, Karnik R, et al.
Author(s): Sabetsky V, Ekblom J
Author(s): Castor TP