Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma

S.K. Mandala Rayabandla, K. Aithal, A. Anandam, G. Shavi, U. Nayanabhirama, K. Arumugam, P. Musmade, K. Bhat, S.R. Bola Sadashiva

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The present study was aimed to evaluate the anti-tumor efficacy and systemic toxicity of chitosan-based plumbagin microspheres in comparison to free plumbagin. The optimized formulation had a mean particle size of 106.35 μm with an encapsulation efficiency of 80.12%. Pharmacokinetic studies showed a 22.2-fold increase in elimination half-life (t1/2) of plumbagin from chitosan microspheres as compared to free plumbagin. Administration of plumbagin microspheres resulted in a significant tumor growth inhibition and reduced systemic toxicity. These results suggest that chitosan-based microspheres could be a promising strategy for the systemic delivery of anti-cancer agents like plumbagin. © 2010 Informa UK Ltd.
Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalDrug Delivery
Volume17
Issue number3
DOIs
Publication statusPublished - 2010

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Chitosan
Microspheres
Melanoma
Pharmacokinetics
Neoplasms
Particle Size
Half-Life
plumbagin
In Vitro Techniques
Growth

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Mandala Rayabandla, S.K. ; Aithal, K. ; Anandam, A. ; Shavi, G. ; Nayanabhirama, U. ; Arumugam, K. ; Musmade, P. ; Bhat, K. ; Bola Sadashiva, S.R. / Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma. In: Drug Delivery. 2010 ; Vol. 17, No. 3. pp. 103-113.
@article{09d36e1330744dedb78018dadf04f8a3,
title = "Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma",
abstract = "The present study was aimed to evaluate the anti-tumor efficacy and systemic toxicity of chitosan-based plumbagin microspheres in comparison to free plumbagin. The optimized formulation had a mean particle size of 106.35 μm with an encapsulation efficiency of 80.12{\%}. Pharmacokinetic studies showed a 22.2-fold increase in elimination half-life (t1/2) of plumbagin from chitosan microspheres as compared to free plumbagin. Administration of plumbagin microspheres resulted in a significant tumor growth inhibition and reduced systemic toxicity. These results suggest that chitosan-based microspheres could be a promising strategy for the systemic delivery of anti-cancer agents like plumbagin. {\circledC} 2010 Informa UK Ltd.",
author = "{Mandala Rayabandla}, S.K. and K. Aithal and A. Anandam and G. Shavi and U. Nayanabhirama and K. Arumugam and P. Musmade and K. Bhat and {Bola Sadashiva}, S.R.",
note = "Cited By :15 Export Date: 10 November 2017 CODEN: DDELE Correspondence Address: Bola Sadashiva, S. R.; Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal-576104, Karnataka, India; email: satishraomlsc@gmail.com Chemicals/CAS: chitosan, 9012-76-4; plumbagin, 481-42-5; Antineoplastic Agents, Phytogenic; Chitosan, 9012-76-4; Cross-Linking Reagents; Delayed-Action Preparations; Glutaral, 111-30-8; Naphthoquinones; plumbagin, 481-42-5 Manufacturers: Sigma, United States References: Akbuga, J., Bergisadi, N., 5-Fluorouracil-loaded chitosan microspheres: Preparation and release characteristics (1996) J Microencapsul, 13, pp. 161-168; Akbuga, J., Bergisadi, N., Effect of formulation variables on cisplatin loaded chitosan microsphere properties (1999) J Microencapsul, 16, pp. 697-703; Chandrasekaran, B., Nagarajan, B., Metabolism of echitamine and plumbagin in rats (1981) J Biosci, 3, pp. 395-400; Chen, W.R., Adams, R.L., Carubelli, R., Nordquist, R.E., Laserphotosensitizer assisted immunotherapy: A novel modality for cancer treatment (1997) Cancer Lett, 115, pp. 25-30; Dass, C.R., Choong, P.F., The use of chitosan formulations in cancer therapy (2008) J Microencapsul, 25, pp. 275-279; Desai, K.G., Park, H.J., Preparation of cross-linked chitosan microspheres by spray drying: Effect of cross-linking agent on the properties of spray dried microspheres (2005) J Microencapsul, 22, pp. 377-395; Devi, P.U., Rao, B.S., Response of mouse sarcoma-180 to bleomycin in combination with radiation and hyperthermia (1993) Strahlenther Onkol, 169, pp. 601-607; Devi, P.U., Solomon, F.E., Sharada, A.C., In vivo tumor inhibitory and radiosensitizing effects of an Indian medicinal plant, Plumbago rosea on experimental mouse tumors (1994) Indian J Exp Biol, 32, pp. 523-528; Higuchi, T., Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices (1963) J Pharm Sci, 52, pp. 1145-1149; Hsieh, Y.J., Lin, L.C., Tsai, T.H., Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry (2006) J Chromatogr B Analyt Technol Biomed Life Sci, 844, pp. 1-5; Hsu, Y.L., Cho, C.Y., Kuo, P.L., Huang, Y.T., Lin, C.C., Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo (2006) J Pharmacol Exp Ther, 318, pp. 484-494; Jameela, S.R., Kumary, T.V., Lal, A.V., Jayakrishnan, A., Progesterone-loaded chitosan microspheres: A long acting biodegradable controlled delivery system (1998) J Contr Rel, 52, pp. 17-24; Kawiak, A., Piosik, J., Stasilojc, G., Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II (2007) Toxicol Appl Pharmacol, 223, pp. 267-276; Kini, D.P., Pandey, S., Shenoy, B.D., Singh, U.V., Udupa, N., Umadevi, P., Kamath, R., Nagarajkumari Ramanarayan, K., Antitumor and antifertility activities of plumbagin controlled release formulations (1997) Indian J Exp Biol, 35, pp. 374-379; Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., Peppas, N.A., Mechanisms of solute release from porous hydrophilic polymers (1983) Int J Pharm, 15, pp. 25-35; Krishnaswamy, M., Purushothaman, K.K., Plumbagin: A study of its anticancer, antibacterial & antifungal properties (1980) Indian J Exp Biol, 18, pp. 876-877; Kuo, P.L., Hsu, Y.L., Cho, C.Y., Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells (2006) Mol Cancer Ther, 5, pp. 3209-3221; Lin, S.Y., Chan, H.Y., Shen, F.H., Chen, M.H., Wang, Y.J., Yu, C.K., Chitosan prevents the development of AOM-induced aberrant crypt foci in mice and suppressed the proliferation of AGS cells by inhibiting DNA synthesis (2007) J Cell Biochem, 100, pp. 1573-1580; Murata, J., Saiki, I., Nishimura, S., Nishi, N., Tokura, S., Azuma, I., Inhibitory effect of chitin heparinoids on the lung metastasis of B16-BL6 melanoma (1989) Jpn J Cancer Res, 80, pp. 866-872; Nair, S., Nair, R.R., Srinivas, P., Srinivas, G., Pillai, M.R., Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway (2008) Mol Carcinog, 47, pp. 22-33; Naresh, R.A., Udupa, N., Devi, P.U., Niosomal plumbagin with reduced toxicity and improved anticancer activity in BALB/C mice (1996) J Pharm Pharmacol, 48, pp. 1128-1132; Nicholas, G.L., Sustained release dosage forms (1987) The Theory and Practice of Industrial Pharmacy, pp. 433-437. , Lachman, L., Lieberman, H.A., Kanig, J.L., eds. New York: Marcel Dekker; Nishioka, Y., Kyotani, S., Masui, H., Okamura, M., Miyazaki, M., Okazaki, K., Ohnishi, S., Ito, K., Preparation and release characteristics of cisplatin albumin microspheres containing chitin and treated with chitosan (1989) Chem Pharm Bull (Tokyo), 37, pp. 3074-3077; Patashnik, S., Rabinovich, L., Golomb, G., Preparation and evaluation of chitosan microspheres containing bisphosphonates (2005) J Drug Target, 4, pp. 371-380; Powolny, A.A., Singh, S.V., Plumbagin-induced apoptosis in human prostate cancer cells is associated with modulation of cellular redox status and generation of reactive oxygen species (2008) Pharm Res, 25, pp. 2171-2180; Prabaharan, M., Mano, J.F., Chitosan-based particles as controlled drug delivery systems (2005) Drug Deliv, 12, pp. 41-57; Prabaharan, M., Mano, J.F., Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: Synthesis and slow release of its inclusion complex with a model hydrophobic drug (2005) Macromol Biosci, 5, pp. 965-973; Prasad, V.S., Devi, P.U., Rao, B.S., Kamath, R., Radiosensitizing effect of plumbagin on mouse melanoma cells grown in vitro (1996) Indian J Exp Biol, 34, pp. 857-858; Purushothaman, K.K., Mohana, K., Susan, T., Biological profile of plumbagin (1985) Bull Med Ethno-bot Res, 6, pp. 177-188; Qi, L., Xu, Z., Chen, M., In vitro and in vivo suppression of hepatocellular carcinoma growth by chitosan nanoparticles (2007) Eur J Cancer, 43, pp. 184-193; Sandur, S.K., Ichikawa, H., Sethi, G., Ahn, K.S., Aggarwal, B.B., Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents (2006) J Biol Chem, 281, pp. 17023-17033; Schipper, N.G., Olsson, S., Hoogstraate, J.A., Deboer, A.G., Varum, K.M., Artursson, P., Chitosans as absorption enhancers for poorly absorbable drugs 2: Mechanism of absorption enhancement (1997) Pharm Res, 14, pp. 923-929; Singh, U.V., Udupa, N., Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma (1997) Indian J Physiol Pharmacol, 41, pp. 171-175; Singh, U.V., Udupa, N., Methotrexate loaded chitosan and chitin microspheres-in vitro characterization and pharmacokinetics in mice bearing Ehrlich ascites carcinoma (1998) J Microencapsul, 15, pp. 581-594; Sinha, V.R., Singla, A.K., Wadhawan, S., Chitosan microspheres as a potential carrier for drugs (2004) Int J Pharm, 274, pp. 1-33; Solomon, F.E., Sharada, A.C., Devi, P.U., Toxic effects of crude root extract of Plumbago rosea (Rakta chitraka) on mice and rats (1993) J Ethnopharmacol, 38, pp. 79-84; Srinivas, P., Gopinath, G., Banerji, A., Dinakar, A., Srinivas, G., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells (2004) Mol Carcinog, 40, pp. 201-211; Sugie, S., Okamoto, K., Rahman, K.M., Tanaka, T., Kawai, K., Yamahara, J., Mori, H., Inhibitory effects of plumbagin and juglone on azoxymethane-induced intestinal carcinogenesis in rats (1998) Cancer Lett, 127, pp. 177-183; Thanoo, B.C., Sunny, M.C., Jayakrishnan, A., Cross-linked chitosan microspheres: Preparation and evaluation as a matrix for the controlled release of pharmaceuticals (1992) J Pharm Pharmacol, 44, pp. 283-286; Thasni, K.A., Rakesh, S., Rojini, G., Ratheeshkumar, T., Srinivas, G., Priya, S., Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents (2008) Ann Oncol, 19, pp. 696-705; Tiwari, S.B., Pai, R.M., Udupa, N., Temperature sensitive liposomes of plumbagin: Characterization and in vivo evaluation in mice bearing melanoma B16F1 (2002) J Drug Target, 10, pp. 585-591; Vijayakumar, R., Senthilvelan, M., Ravindran, R., Devi, R.S., Plumbago zeylanica action on blood coagulation profile with and without blood volume reduction (2006) Vascul Pharmacol, 45, pp. 86-90; Zhu, K.J., Li, Y., Jiang, H.L., Yasuda, H., Ichimaru, A., Yamamoto, K., Lecomte, P., Jerome, R., Preparation, characterization and in vitro release properties of ibuprofen-loaded microspheres based on polylactide, poly(ε-caprolactone) and their copolymers (2005) J Microencapsul, 22, pp. 25-36",
year = "2010",
doi = "10.3109/10717540903548447",
language = "English",
volume = "17",
pages = "103--113",
journal = "Drug Delivery",
issn = "1071-7544",
publisher = "Informa Healthcare",
number = "3",

}

Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma. / Mandala Rayabandla, S.K.; Aithal, K.; Anandam, A.; Shavi, G.; Nayanabhirama, U.; Arumugam, K.; Musmade, P.; Bhat, K.; Bola Sadashiva, S.R.

In: Drug Delivery, Vol. 17, No. 3, 2010, p. 103-113.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma

AU - Mandala Rayabandla, S.K.

AU - Aithal, K.

AU - Anandam, A.

AU - Shavi, G.

AU - Nayanabhirama, U.

AU - Arumugam, K.

AU - Musmade, P.

AU - Bhat, K.

AU - Bola Sadashiva, S.R.

N1 - Cited By :15 Export Date: 10 November 2017 CODEN: DDELE Correspondence Address: Bola Sadashiva, S. R.; Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal-576104, Karnataka, India; email: satishraomlsc@gmail.com Chemicals/CAS: chitosan, 9012-76-4; plumbagin, 481-42-5; Antineoplastic Agents, Phytogenic; Chitosan, 9012-76-4; Cross-Linking Reagents; Delayed-Action Preparations; Glutaral, 111-30-8; Naphthoquinones; plumbagin, 481-42-5 Manufacturers: Sigma, United States References: Akbuga, J., Bergisadi, N., 5-Fluorouracil-loaded chitosan microspheres: Preparation and release characteristics (1996) J Microencapsul, 13, pp. 161-168; Akbuga, J., Bergisadi, N., Effect of formulation variables on cisplatin loaded chitosan microsphere properties (1999) J Microencapsul, 16, pp. 697-703; Chandrasekaran, B., Nagarajan, B., Metabolism of echitamine and plumbagin in rats (1981) J Biosci, 3, pp. 395-400; Chen, W.R., Adams, R.L., Carubelli, R., Nordquist, R.E., Laserphotosensitizer assisted immunotherapy: A novel modality for cancer treatment (1997) Cancer Lett, 115, pp. 25-30; Dass, C.R., Choong, P.F., The use of chitosan formulations in cancer therapy (2008) J Microencapsul, 25, pp. 275-279; Desai, K.G., Park, H.J., Preparation of cross-linked chitosan microspheres by spray drying: Effect of cross-linking agent on the properties of spray dried microspheres (2005) J Microencapsul, 22, pp. 377-395; Devi, P.U., Rao, B.S., Response of mouse sarcoma-180 to bleomycin in combination with radiation and hyperthermia (1993) Strahlenther Onkol, 169, pp. 601-607; Devi, P.U., Solomon, F.E., Sharada, A.C., In vivo tumor inhibitory and radiosensitizing effects of an Indian medicinal plant, Plumbago rosea on experimental mouse tumors (1994) Indian J Exp Biol, 32, pp. 523-528; Higuchi, T., Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices (1963) J Pharm Sci, 52, pp. 1145-1149; Hsieh, Y.J., Lin, L.C., Tsai, T.H., Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry (2006) J Chromatogr B Analyt Technol Biomed Life Sci, 844, pp. 1-5; Hsu, Y.L., Cho, C.Y., Kuo, P.L., Huang, Y.T., Lin, C.C., Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo (2006) J Pharmacol Exp Ther, 318, pp. 484-494; Jameela, S.R., Kumary, T.V., Lal, A.V., Jayakrishnan, A., Progesterone-loaded chitosan microspheres: A long acting biodegradable controlled delivery system (1998) J Contr Rel, 52, pp. 17-24; Kawiak, A., Piosik, J., Stasilojc, G., Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II (2007) Toxicol Appl Pharmacol, 223, pp. 267-276; Kini, D.P., Pandey, S., Shenoy, B.D., Singh, U.V., Udupa, N., Umadevi, P., Kamath, R., Nagarajkumari Ramanarayan, K., Antitumor and antifertility activities of plumbagin controlled release formulations (1997) Indian J Exp Biol, 35, pp. 374-379; Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., Peppas, N.A., Mechanisms of solute release from porous hydrophilic polymers (1983) Int J Pharm, 15, pp. 25-35; Krishnaswamy, M., Purushothaman, K.K., Plumbagin: A study of its anticancer, antibacterial & antifungal properties (1980) Indian J Exp Biol, 18, pp. 876-877; Kuo, P.L., Hsu, Y.L., Cho, C.Y., Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells (2006) Mol Cancer Ther, 5, pp. 3209-3221; Lin, S.Y., Chan, H.Y., Shen, F.H., Chen, M.H., Wang, Y.J., Yu, C.K., Chitosan prevents the development of AOM-induced aberrant crypt foci in mice and suppressed the proliferation of AGS cells by inhibiting DNA synthesis (2007) J Cell Biochem, 100, pp. 1573-1580; Murata, J., Saiki, I., Nishimura, S., Nishi, N., Tokura, S., Azuma, I., Inhibitory effect of chitin heparinoids on the lung metastasis of B16-BL6 melanoma (1989) Jpn J Cancer Res, 80, pp. 866-872; Nair, S., Nair, R.R., Srinivas, P., Srinivas, G., Pillai, M.R., Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway (2008) Mol Carcinog, 47, pp. 22-33; Naresh, R.A., Udupa, N., Devi, P.U., Niosomal plumbagin with reduced toxicity and improved anticancer activity in BALB/C mice (1996) J Pharm Pharmacol, 48, pp. 1128-1132; Nicholas, G.L., Sustained release dosage forms (1987) The Theory and Practice of Industrial Pharmacy, pp. 433-437. , Lachman, L., Lieberman, H.A., Kanig, J.L., eds. New York: Marcel Dekker; Nishioka, Y., Kyotani, S., Masui, H., Okamura, M., Miyazaki, M., Okazaki, K., Ohnishi, S., Ito, K., Preparation and release characteristics of cisplatin albumin microspheres containing chitin and treated with chitosan (1989) Chem Pharm Bull (Tokyo), 37, pp. 3074-3077; Patashnik, S., Rabinovich, L., Golomb, G., Preparation and evaluation of chitosan microspheres containing bisphosphonates (2005) J Drug Target, 4, pp. 371-380; Powolny, A.A., Singh, S.V., Plumbagin-induced apoptosis in human prostate cancer cells is associated with modulation of cellular redox status and generation of reactive oxygen species (2008) Pharm Res, 25, pp. 2171-2180; Prabaharan, M., Mano, J.F., Chitosan-based particles as controlled drug delivery systems (2005) Drug Deliv, 12, pp. 41-57; Prabaharan, M., Mano, J.F., Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: Synthesis and slow release of its inclusion complex with a model hydrophobic drug (2005) Macromol Biosci, 5, pp. 965-973; Prasad, V.S., Devi, P.U., Rao, B.S., Kamath, R., Radiosensitizing effect of plumbagin on mouse melanoma cells grown in vitro (1996) Indian J Exp Biol, 34, pp. 857-858; Purushothaman, K.K., Mohana, K., Susan, T., Biological profile of plumbagin (1985) Bull Med Ethno-bot Res, 6, pp. 177-188; Qi, L., Xu, Z., Chen, M., In vitro and in vivo suppression of hepatocellular carcinoma growth by chitosan nanoparticles (2007) Eur J Cancer, 43, pp. 184-193; Sandur, S.K., Ichikawa, H., Sethi, G., Ahn, K.S., Aggarwal, B.B., Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents (2006) J Biol Chem, 281, pp. 17023-17033; Schipper, N.G., Olsson, S., Hoogstraate, J.A., Deboer, A.G., Varum, K.M., Artursson, P., Chitosans as absorption enhancers for poorly absorbable drugs 2: Mechanism of absorption enhancement (1997) Pharm Res, 14, pp. 923-929; Singh, U.V., Udupa, N., Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma (1997) Indian J Physiol Pharmacol, 41, pp. 171-175; Singh, U.V., Udupa, N., Methotrexate loaded chitosan and chitin microspheres-in vitro characterization and pharmacokinetics in mice bearing Ehrlich ascites carcinoma (1998) J Microencapsul, 15, pp. 581-594; Sinha, V.R., Singla, A.K., Wadhawan, S., Chitosan microspheres as a potential carrier for drugs (2004) Int J Pharm, 274, pp. 1-33; Solomon, F.E., Sharada, A.C., Devi, P.U., Toxic effects of crude root extract of Plumbago rosea (Rakta chitraka) on mice and rats (1993) J Ethnopharmacol, 38, pp. 79-84; Srinivas, P., Gopinath, G., Banerji, A., Dinakar, A., Srinivas, G., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells (2004) Mol Carcinog, 40, pp. 201-211; Sugie, S., Okamoto, K., Rahman, K.M., Tanaka, T., Kawai, K., Yamahara, J., Mori, H., Inhibitory effects of plumbagin and juglone on azoxymethane-induced intestinal carcinogenesis in rats (1998) Cancer Lett, 127, pp. 177-183; Thanoo, B.C., Sunny, M.C., Jayakrishnan, A., Cross-linked chitosan microspheres: Preparation and evaluation as a matrix for the controlled release of pharmaceuticals (1992) J Pharm Pharmacol, 44, pp. 283-286; Thasni, K.A., Rakesh, S., Rojini, G., Ratheeshkumar, T., Srinivas, G., Priya, S., Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents (2008) Ann Oncol, 19, pp. 696-705; Tiwari, S.B., Pai, R.M., Udupa, N., Temperature sensitive liposomes of plumbagin: Characterization and in vivo evaluation in mice bearing melanoma B16F1 (2002) J Drug Target, 10, pp. 585-591; Vijayakumar, R., Senthilvelan, M., Ravindran, R., Devi, R.S., Plumbago zeylanica action on blood coagulation profile with and without blood volume reduction (2006) Vascul Pharmacol, 45, pp. 86-90; Zhu, K.J., Li, Y., Jiang, H.L., Yasuda, H., Ichimaru, A., Yamamoto, K., Lecomte, P., Jerome, R., Preparation, characterization and in vitro release properties of ibuprofen-loaded microspheres based on polylactide, poly(ε-caprolactone) and their copolymers (2005) J Microencapsul, 22, pp. 25-36

PY - 2010

Y1 - 2010

N2 - The present study was aimed to evaluate the anti-tumor efficacy and systemic toxicity of chitosan-based plumbagin microspheres in comparison to free plumbagin. The optimized formulation had a mean particle size of 106.35 μm with an encapsulation efficiency of 80.12%. Pharmacokinetic studies showed a 22.2-fold increase in elimination half-life (t1/2) of plumbagin from chitosan microspheres as compared to free plumbagin. Administration of plumbagin microspheres resulted in a significant tumor growth inhibition and reduced systemic toxicity. These results suggest that chitosan-based microspheres could be a promising strategy for the systemic delivery of anti-cancer agents like plumbagin. © 2010 Informa UK Ltd.

AB - The present study was aimed to evaluate the anti-tumor efficacy and systemic toxicity of chitosan-based plumbagin microspheres in comparison to free plumbagin. The optimized formulation had a mean particle size of 106.35 μm with an encapsulation efficiency of 80.12%. Pharmacokinetic studies showed a 22.2-fold increase in elimination half-life (t1/2) of plumbagin from chitosan microspheres as compared to free plumbagin. Administration of plumbagin microspheres resulted in a significant tumor growth inhibition and reduced systemic toxicity. These results suggest that chitosan-based microspheres could be a promising strategy for the systemic delivery of anti-cancer agents like plumbagin. © 2010 Informa UK Ltd.

U2 - 10.3109/10717540903548447

DO - 10.3109/10717540903548447

M3 - Article

VL - 17

SP - 103

EP - 113

JO - Drug Delivery

JF - Drug Delivery

SN - 1071-7544

IS - 3

ER -