• SHAYMA KHAN Shri Rawatpura Sarkar College of Prarmacy, Sagar (M. P.)
  • NAINA DUBEY Acropolis Institute of Pharmaceutical Education and Research, Indore (M. P.)
  • BASANT KHARE Adina College of Pharmacy, Sagar (M. P.)
  • HARSHITA JAIN Adina Institute of Pharmaceutical Sciences, Sagar (M. P.)
  • PRATEEK KUMAR JAIN Adina College of Pharmacy, Sagar (M. P.)



Cancer, Nanoparticles, Lactobionic, Cytotoxicity, In vivo


Objective: Delivery of anticancer molecule to the liver remains a “holy grail” in molecular medicine and nanobiotechnology with conventional therapy, as conventional cancer chemotherapy does not prove effective as drug molecule does not reach to the target site at therapeutic concentration. Tumor vasculature differs from the vasculature of normal tissue both in morphology and biochemistry. Most of these differences appear too related to angiogenesis (formation of new blood vessels from pre-existing ones). For the present study nanoparticles (NPs) were chosen as a delivery system, because they have many advantages, e. g. they can pass through the smallest capillary vessels because of their ultra-tiny volume, can penetrate cells and tissue gap to arrive at, pH, ion and/or temperature sensitivity of materials, can improve the utility of drugs and reduce toxic side effects.

Methods: PLGA (poly lactide co glycolic acid) was used for the preparation of NPs because of its biodegradability and biocompatibility. It degrades by hydrolysis of ester linkages in the presence of water in to two monomers lactic acid and glycolic acid. There are a number of ligands available for hepatic delivery, among them lactobionic acid (containing galactose moiety) was selected for present work. Preparation of plain nanoparticles was carried out using emulsification–diffusion method. Optimization of the polymer concentration is the first step during the study and it was performed by varying the polymer concentration where as keeping other variables constant. The prepared formulation was optimized on the basis of particle size and polydispersity index. Amount of drug was optimized on the basis of particle size and percentage entrapment efficiency.

Results: Particle size and zeta potential of the nanoparticle were determined by zetasizer showed that particles are in nano range (blow 200 nm) and have acceptable range of zeta potential. Shape and surface morphology were determined by TEM and SEM analysis. The conjugation of lactobionic acid with PLGA polymer was proved by FTIR. The in vitro release profiles of entrapped drug from formulations were determined using dialysis membrane. For stability studies, the LDNPs (conjugated NPs) are stored at the temperatures 4±1 °C and room temperature. Human hepatoma cell line HepG2 by SRB assay was selected and it clearly suggests a dose dependent cytotoxicity response i.e. decrease in cell survival fraction with increasing concentration of drug. The in vivo study are important in evaluating the targeting efficacy of designed dosage form and also helps in establishing the correlation between the results obtained from in vitro experimentation to that from in vivo studies. The formulations were administered by tail vein to mice of four groups Group I: PBS 7.4 (control); Group II: 5-FU solution; Group III: DNPs; Group IV: LDNPs.

Conclusion: The proposed targeting strategy is expected to enhance the therapeutic index of conventional anticancer drug as well as reduce its cytotoxic effects to normal cells.


Download data is not yet available.


Das S, Deshmukh R, Jha AK. Role of natural polymers in the development of multiparticulate systems for colon drug targeting. Syst Rev Pharm. 2010;1(1):79-85. doi: 10.4103/0975-8453.59516.

Allemann E, Gurny R, Doelkar E. Drug loaded nanoparticles preparation method and drug targeting tissues. Eur J Pharm Biopharm. 1993;39:173-91.

Banfi A, Degenfeld G, Blau HM. Critical role of microenvironmental factors in angiogenesis. Curr Ather Rep. 2005;7:227-34.

Calvo J, Akerman ME, Laakkonen P. Nanocrystal target in vivo. Proc Natl Acad Sci USA. 2001;99:12613-23.

Ciechanover A, Schwartz AL, Lodish HF. Sorting and recycling of cell surface receptors and endocytosed ligands: the asialoglycoprotein and transferrin receptors. J Cell Biochem. 1983;23(1-4):107-30. doi: 10.1002/jcb.240230111, PMID 6327736.

Crowther M, Brown NJ, Bishop ET, Lewis CE. Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol. 2001;70(4):478-90. PMID 11590184.

Davis BG, Robinson MA. Drug delivery systems based on sugar-macromolecule conjugates. Curr Opin Drug Discov Devel. 2002;5(2):279-88. PMID 11926134.

De Abrew SD. Assays for transferrin and transferrin receptors in tumour and other mouse tissues. Int J Nucl Med Biol. 1981;8(4):217-21. doi: 10.1016/0047-0740(81)90025-5, PMID 6276310.

Earp HS, Dawson TL, Li X, Yu H. Heterodimerization and functional interaction between EGF receptor family members: A new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat. 1995;35(1):115-32. doi: 10.1007/BF00694752, PMID 7612898.

Engers R, Gabbert HE. Mechanisms of tumor metastasis: cell biological aspects and clinical implications. J Cancer Res Clin Oncol. 2000;126(12):682-92. doi: 10.1007/s004320000148, PMID 11153140.

Fallon RJ, Schwartz AL. Asialoglycoprotein receptor phosphorylation and receptor-mediated endocytosis in hepatoma cells. Effect of phorbol esters. J Biol Chem. 1988;263(26):13159-66. doi: 10.1016/S0021-9258(18)37685-3, PMID 3166456.

Florey K. Analytical profiles drug substances. Vol. 2. New York: Academic Press; 1973. p. 221-40.

Folkman J. Incipient angiogenesis. J Natl Cancer Inst. 2000;92(2):94-5. doi: 10.1093/jnci/92.2.94, PMID 10639502.

Baban DF, Seymour LW. Control of tumour vascular permeability. Adv Drug Deliv Rev. 1998;34(1):109-19. doi: 10.1016/s0169-409x(98)00003-9, PMID 10837673.

Fry DW, White JC, Goldman ID. Rapid separation of low molecular weight solutes from liposomes without dilution. Anal Biochem. 1978;90(2):809-15. doi: 10.1016/0003-2697(78)90172-0, PMID 727510.

Gabius HJ, Andre S, Kaltner H, Siebert HC. The sugar code: functional lectinomics. Biochim Biophys Acta. 2002;1572(2-3):165-77. doi: 10.1016/s0304-4165(02)00306-9, PMID 12223267.

Garin-Chesa P, Campbell I, Saigo PE, Lewis JL, Old LJ, Rettig WJ. Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. Am J Pathol. 1993;142(2):557-67. PMID 8434649.

Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. Biodegradable long-circulating polymeric nanospheres. Science. 1994;263(5153):1600-3. doi: 10.1126/science.8128245, PMID 8128245.

Gupta MK, Qin RY. Mechanism and it’s regulation of tumor induced angiogenesis. World J Gastroenterol. 2005;9:1144-55.

Laroui, Dalmasso, Nguyen, Yutao Yan, Shanthi V Sitaraman, Merlin. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010;138(3):843-53.e1. doi: 10.1053/j.gastro.2009.11.003, PMID 19909746.

Han JH, Oh YK, Kim DS, Kim CK. Enhanced hepatocyte uptake and liver targeting of methotrexate using galactosylated albumin as a carrier. Int J Pharm. 1999;188(1):39-47. doi: 10.1016/s0378-5173(99)00206-9. PMID 10528081.

Indian Pharmacopoiea. Vol. 1. New Delhi: government of India, ministry of health and family welfare; 1996. p. 323.

Kim IS, Kim SH. Development of polymeric nanoparticulate drug delivery systems: evaluation of nanoparticles based on biotinylated poly (ethylene glycol) with sugar moiety. Int J Pharm. 2003;257(1-2):195-203. doi: 10.1016/s0378-5173(03)00128-5, PMID 12711174.

Kalsi PS. Spectroscopy of organic compounds. 6th ed. New age international Pvt. Ltd. New Delhi; 2007. p. 66-172.

Kannagi R, Izawa M, Koike T, Miyazaki K, Kimura N. Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci. 2004;95(5):377-84. doi: 10.1111/j.1349-7006.2004.tb03219.x, PMID 15132763.

Yang J, Han S, Zheng H, Dong H, Liu J. Preparation and application of micro/nanoparticles based on natural polysaccharides. Carbohydr Polym. 2015;123:53-66. doi: 10.1016/j.carbpol.2015.01.029, PMID 25843834.

Kilpatrick DC. Mannan-binding lectin: clinical significance and applications. Biochim Biophys Acta. 2002;1572(2-3):401-13. doi: 10.1016/s0304-4165(02)00321-5, PMID 12223282.

Kim IS, Jeong YI, Cho CS, Kim SH. Core-shell type polymeric Nano particles composed of poly (L-lactic acid) and poly (N-isopropylacrylamide). Int J Pharm. 2002;211:1-8.

Larsen AK, Escargueil AE, Skladanowski A. Resistance mechanisms associated with altered intracellular distribution of anticancer agents. Pharmacol Ther. 2000;85(3):217-29. doi: 10.1016/s0163-7258(99)00073-x, PMID 10739876.

Lee JH, Ku JL, Park YJ, Lee KU, Kim WH, Park JG. Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA. World J Gastroenterol. 1999;45(4):289-95. doi: 10.3748/wjg.v5.i4.289, PMID 11819450.

Rani M, Agarwal A, Negi YS. Chitosan based hydrogel polymeric beads–as drug delivery system. Bio-Resour. 2010;5(4).

Nicolson G. Molecular cell biology and cancer metastasis. An interview with Garth Nicolson. Int J Dev Biol. 2004;48(5-6):355-63. doi: 10.1387/ijdb.041803mm, PMID 15349811.

Lin X, Wu Q, Chen Z, Gong X, Lin X. Preparation, characterization and controlled release of liver-targeting nanoparticles from the amphiphilic random copolymer. Polymer. 2008;49(22):4769-75. doi: 10.1016/ j.polymer.2008.09.006.

Molema G, de Leij LFMH, Meijer DKF. Tumor vascular endothelium: barrier or target in tumor directed drug delivery and immunotherapy. Pharma Res. 1997;14(1):2-10. doi: 10.1023/a:1012038930172, PMID 9034214.

Nakashima Matsushita N, Homma T, Yu S, Matsuda T, Sunahara N, Nakamura T, Tsukano M, Ratnam M, Matsuyama T. Selective expression of folate receptor β and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum. 1999;42(8):1609-16. doi: 10.1002/1529-0131(199908)42:8<1609::AID-ANR7>3.0.CO;2-L, PMID 10446858.

Pan H, Gao F, Papageorgis P, Abdolmaleky HM, Faller DV, Thiagalingam S. Aberrant activation of gamma-catenin promotes genomic instability and oncogenic effects during tumor progression. Cancer Biol Ther. 2007;6(10):1638-43. doi: 10.4161/cbt.6.10.4904, PMID 18245958.

Ramaa CS, Tilekar KN, Patil VM. Liver cancer: different approaches for targeting. Int J Pharm Technol. 2010:834-42.

Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann DR, Hutton JC, Elliott JF, Eisenbarth GS. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 2005;435(7039):220-3. doi: 10.1038/nature03523, PMID 15889095.

Saif MW. Pancreatic cancer: highlights from the 42nd annual meeting of the American Society of Clinical Oncology, 2006. JOP. 2006;7(4):337-48. PMID 16832131.

Sarkar Biresh K, Devananda J, Angshu B. New drug delivery system. IJRAP. 2011;2(5):1513-7.

Schwartz AL, Rup D, Lodish HF. Difficulties in the quantification of asialoglycoprotein receptors on the rat hepatocyte. J Biol Chem. 1980;255(19):9033-6. doi: 10.1016/S0021-9258(19)70522-5, PMID 7410410.

Huang W, Wang W, Wang P, Tian Q, Zhang C, Wang C. Glycyrrhetinic acid-modified poly(ethylene glycol)–b-poly(γ-benzyl l-glutamate) micelles for liver targeting therapy. Acta Biomaterialia. 2010;6(10):3927-35. doi: 10.1016/ j.actbio.2010.04.021.

Toffoli G, Cernigoi C, Russo A, Gallo A, Bagnoli M, Boiocchi M. Overexpression of folate binding protein in ovarian cancers. Int J Cancer. 1997;74(2):193-8. doi: 10.1002/(sici)1097-0215(19970422)74:2<193::aid-ijc10>;2-f, PMID 9133455.

Vyas SP, Khar RK. Targeted and controlled drug delivery novel carrier systems. CBS publishers and distributors. New Delhi. 2001;331-84.

Weigel PH, Yik JHN. Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochim Biophys Acta. 2002;1572(2-3):341-63. doi: 10.1016/s0304-4165(02)00318-5, PMID 12223279.

Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening Nature. Nat Protoc. 2006;1(3):1112-6. doi: 10.1038/nprot.2006.179, PMID 17406391.



How to Cite

KHAN, S., N. DUBEY, B. KHARE, H. JAIN, and P. K. JAIN. “PREPARATION AND CHARACTERIZATION OF ALGINATE CHITOSAN CROSSLINKED NANOPARTICLES BEARING DRUG FOR THE EFFECTIVE MANAGEMENT OF ULCERATIVE COLITIS”. International Journal of Current Pharmaceutical Research, vol. 14, no. 5, Sept. 2022, pp. 48-61, doi:10.22159/ijcpr.2022v14i5.2040.



Original Article(s)