- Email: [email protected]
folic acid conjugate for targeting drug delivery system
Abstracts / Journal of Controlled Release 172 (2013) e14–e97
then the drug-loaded n-HA (AMX/n-HA) (Fig. 1a) was dispersed into poly(lactic-co-glycolic acid) (PLGA) polymer solution for subsequent electrospinning. The formed AMX/n-HA and AMX/n-HA/PLGA composite nanofibers (Fig. 1b) were characterized using different techniques. We show that AMX can be successfully encapsulated by n-HA and the AMX/n-HA/PLGA nanofibers have a uniform morphology with axial alignment of n-HA (Fig. 1b) and improved mechanical properties. Cytotoxicity assay, cell morphology observation and in vitro hemolytic assay reveal that the formed AMX/n-HA/PLGA composite nanofibers are non-cytotoxic and hemocompatible. The loaded AMX on n-HA incorporated within PLGA nanofibers shows a sustained release profile (Fig. 1c) and is capable to inhibit the growth of the model bacteria Staphylococcus aureus (Fig. 1d).
Fig. 1. TEM micrograph of AMX/n-HA nanorods (a) and AMX/n-HA/PLGA nanofibers (b). (c) shows the in vitro release of AMX from AMX/n-HA nanorods, AMX/PLGA nanofibers, and AMX/n-HA/PLGA nanofibers incubated in PBS buffer (pH = 7.4) at 37 °C. (d) shows the growth inhibition of the model bacteria (S. aureus) after 24 h of incubation as a function of the concentration of pure AMX in different samples.
Keywords: Electrospinning, Poly(lactic-co-glycolic acid), Nano-hydroxyapatite, Amoxicillin, Antibacterial property
e31
of good biocompatibility as biomaterials for various applications in biological medicine areas. They exhibited promising controllability in self-assembly into highly uniform spherical micellar structures with an average diameter range of 100 to 200 nm, providing a convenient strategy for drug loading. The doxorubicin that was demonstrated to have a good affinity with the copolymer system based on molecular mechanics calculation was chosen as model drug and its controlled release was performed in various pH conditions, revealing that the release is a pH-mediated process, more activated release at low pH. In addition, folic acid has emerged as an optimal targeting ligand for selective delivery of the therapeutic agents to cancer tissues and sites; therefore this system has enormous potential application for use in targeting drug delivery.
Fig. 1. TEM images of HBP–FA–Rh6G micelle bearing doxorubicin obtained by selfassembly in different solvents: DMF/H2O (left), THF/H2O (center) and DMSO/H2O (right). Scale bar = 100 nm.
Keywords: Controlled drug release, Folic acid, Hyperbranched polyglycidol, Anticancer, Targeting Acknowledgements This work was supported by grants-in-aid for the World Class University Program (No. R32-2008-000-10174-0).
Acknowledgements This research is financially supported by “111 Project” (B07024) and the Program for New Century Excellent Talents in University, State Education Ministry.
References
Reference
doi:10.1016/j.jconrel.2013.08.069
[1] M.D. Salazar, M. Ratnam, The folate receptor: what does it promise in tissue-targeted therapeutics?, Cancer Metastasis Rev. 26 (2007) 141–152. [2] P.S. Low, A.C. Antony, Folate receptor-targeted drugs for cancer and inflammatory diseases, Adv. Drug Deliv. Rev. 56 (2004) 1055–1058.
[1] R. Qi, R. Guo, M. Shen, X. Cao, L. Zhang, J. Xu, J. Yu, X. Shi, Electrospun poly(lactic-co-glycolic acid)/halloysite nanotube composite nanofibers for drug encapsulation and sustained release, J. Mater. Chem. 20 (2010) 10622–10629.
doi:10.1016/j.jconrel.2013.08.068
Dendritic hyperbranched polyglycidol/folic acid conjugate for targeting drug delivery system Ga Young Song, Jing Wang, Jin Young Shin, Song I Song, Il Kim⁎ The World Class University Centre for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Republic of Korea E-mail address: [email protected] (I. Kim). Folic acid (FA) has emerged as an optimal targeting ligand for selective delivery of attached imaging and therapeutic agents to cancer tissues and sites [1]. Cancers found to overexpress folate receptor include cancers of the ovary, lung, breast, kidney, brain, endometrium, colon and hematopoietic cells of myelogenous origin [2]. As a means of developing a new targeting drug delivery system, we have investigated the dendritic hyperbranched polyglycidol (HBP)/FA conjugate bearing dye. The HBP bearing multi-hydroxyl groups on its periphery was synthesized by ring-opening multibranching polymerization of glycidol using trimethylolpropane as an initiator. Folic acids were conjugated on the periphery of HBP by esterification in the presence of hydrolyzing Rhodamine 6G (Rh6G). The obtained conjugate materials with narrow polydispersities (1.10–1.19) were well demonstrated to be in possession
Polymeric nanoparticles of Gemcitabine HCl: Formulation and optimization by factorial design Garima Joshi, Krutika Sawant TIFAC Centre of Relevance and Excellence, Centre of PG Studies and Research, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donors Plaza, Fatehgunj, Vadodara 390002, Gujarat, India E-mail address: [email protected] (G. Joshi). Oral drug delivery is preferred over parenteral drug delivery as it improves patient compliance. Most of anticancer drugs are administered by intravenous injections and infusions because of poor oral bioavailability, which leads to exposure of high concentration of drug to the tissues and toxicity to healthy tissues [1]. A major challenge in anticancer therapy is to improve oral bioavailability and reduce the toxicity to healthy tissues. Nanoparticulate drug delivery systems can be a suitable alternative for oral anticancer therapy. The main goal of the present study is to design an oral nanoparticulate formulation of PLGA based Gemcitabine HCl which would be capable of being absorbed through M cells of Peyer's patches then undergo lymphatic uptake, thereby bypassing liver metabolism and thus improving the bioavailability of the drug [2]. Here, the nanoparticles were prepared by the multiple emulsification solvent evaporation method. The formulation was optimized by 33 full factorial design using particle size (PS) and entrapment efficiency (EE) as response parameters. The size and zeta potential of NPs were measured by the Malvern Zetasizer Nanoseries-ZS. Entrapment efficiency was determined by
then the drug-loaded n-HA (AMX/n-HA) (Fig. 1a) was dispersed into poly(lactic-co-glycolic acid) (PLGA) polymer solution for subsequent electrospinning. The formed AMX/n-HA and AMX/n-HA/PLGA composite nanofibers (Fig. 1b) were characterized using different techniques. We show that AMX can be successfully encapsulated by n-HA and the AMX/n-HA/PLGA nanofibers have a uniform morphology with axial alignment of n-HA (Fig. 1b) and improved mechanical properties. Cytotoxicity assay, cell morphology observation and in vitro hemolytic assay reveal that the formed AMX/n-HA/PLGA composite nanofibers are non-cytotoxic and hemocompatible. The loaded AMX on n-HA incorporated within PLGA nanofibers shows a sustained release profile (Fig. 1c) and is capable to inhibit the growth of the model bacteria Staphylococcus aureus (Fig. 1d).
Fig. 1. TEM micrograph of AMX/n-HA nanorods (a) and AMX/n-HA/PLGA nanofibers (b). (c) shows the in vitro release of AMX from AMX/n-HA nanorods, AMX/PLGA nanofibers, and AMX/n-HA/PLGA nanofibers incubated in PBS buffer (pH = 7.4) at 37 °C. (d) shows the growth inhibition of the model bacteria (S. aureus) after 24 h of incubation as a function of the concentration of pure AMX in different samples.
Keywords: Electrospinning, Poly(lactic-co-glycolic acid), Nano-hydroxyapatite, Amoxicillin, Antibacterial property
e31
of good biocompatibility as biomaterials for various applications in biological medicine areas. They exhibited promising controllability in self-assembly into highly uniform spherical micellar structures with an average diameter range of 100 to 200 nm, providing a convenient strategy for drug loading. The doxorubicin that was demonstrated to have a good affinity with the copolymer system based on molecular mechanics calculation was chosen as model drug and its controlled release was performed in various pH conditions, revealing that the release is a pH-mediated process, more activated release at low pH. In addition, folic acid has emerged as an optimal targeting ligand for selective delivery of the therapeutic agents to cancer tissues and sites; therefore this system has enormous potential application for use in targeting drug delivery.
Fig. 1. TEM images of HBP–FA–Rh6G micelle bearing doxorubicin obtained by selfassembly in different solvents: DMF/H2O (left), THF/H2O (center) and DMSO/H2O (right). Scale bar = 100 nm.
Keywords: Controlled drug release, Folic acid, Hyperbranched polyglycidol, Anticancer, Targeting Acknowledgements This work was supported by grants-in-aid for the World Class University Program (No. R32-2008-000-10174-0).
Acknowledgements This research is financially supported by “111 Project” (B07024) and the Program for New Century Excellent Talents in University, State Education Ministry.
References
Reference
doi:10.1016/j.jconrel.2013.08.069
[1] M.D. Salazar, M. Ratnam, The folate receptor: what does it promise in tissue-targeted therapeutics?, Cancer Metastasis Rev. 26 (2007) 141–152. [2] P.S. Low, A.C. Antony, Folate receptor-targeted drugs for cancer and inflammatory diseases, Adv. Drug Deliv. Rev. 56 (2004) 1055–1058.
[1] R. Qi, R. Guo, M. Shen, X. Cao, L. Zhang, J. Xu, J. Yu, X. Shi, Electrospun poly(lactic-co-glycolic acid)/halloysite nanotube composite nanofibers for drug encapsulation and sustained release, J. Mater. Chem. 20 (2010) 10622–10629.
doi:10.1016/j.jconrel.2013.08.068
Dendritic hyperbranched polyglycidol/folic acid conjugate for targeting drug delivery system Ga Young Song, Jing Wang, Jin Young Shin, Song I Song, Il Kim⁎ The World Class University Centre for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Republic of Korea E-mail address: [email protected] (I. Kim). Folic acid (FA) has emerged as an optimal targeting ligand for selective delivery of attached imaging and therapeutic agents to cancer tissues and sites [1]. Cancers found to overexpress folate receptor include cancers of the ovary, lung, breast, kidney, brain, endometrium, colon and hematopoietic cells of myelogenous origin [2]. As a means of developing a new targeting drug delivery system, we have investigated the dendritic hyperbranched polyglycidol (HBP)/FA conjugate bearing dye. The HBP bearing multi-hydroxyl groups on its periphery was synthesized by ring-opening multibranching polymerization of glycidol using trimethylolpropane as an initiator. Folic acids were conjugated on the periphery of HBP by esterification in the presence of hydrolyzing Rhodamine 6G (Rh6G). The obtained conjugate materials with narrow polydispersities (1.10–1.19) were well demonstrated to be in possession
Polymeric nanoparticles of Gemcitabine HCl: Formulation and optimization by factorial design Garima Joshi, Krutika Sawant TIFAC Centre of Relevance and Excellence, Centre of PG Studies and Research, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donors Plaza, Fatehgunj, Vadodara 390002, Gujarat, India E-mail address: [email protected] (G. Joshi). Oral drug delivery is preferred over parenteral drug delivery as it improves patient compliance. Most of anticancer drugs are administered by intravenous injections and infusions because of poor oral bioavailability, which leads to exposure of high concentration of drug to the tissues and toxicity to healthy tissues [1]. A major challenge in anticancer therapy is to improve oral bioavailability and reduce the toxicity to healthy tissues. Nanoparticulate drug delivery systems can be a suitable alternative for oral anticancer therapy. The main goal of the present study is to design an oral nanoparticulate formulation of PLGA based Gemcitabine HCl which would be capable of being absorbed through M cells of Peyer's patches then undergo lymphatic uptake, thereby bypassing liver metabolism and thus improving the bioavailability of the drug [2]. Here, the nanoparticles were prepared by the multiple emulsification solvent evaporation method. The formulation was optimized by 33 full factorial design using particle size (PS) and entrapment efficiency (EE) as response parameters. The size and zeta potential of NPs were measured by the Malvern Zetasizer Nanoseries-ZS. Entrapment efficiency was determined by