Synthesis and antitumour activity of medium molecular weight phthalimide polymers of camptothecin

Lee, Neung-Ju; Ju, Sung-Suk; Cho, Won‐Jei; Kim, Seung‐Chul; Kang, Kyung‐Tae; Brady, Thomas P.; Theodorakis, Emmanuel A.

doi:10.1002/pi.1138

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…Theodorakis and co-workers developed phthalimide-co-acrylic acid polymers synthesized through photopolymerization to afford a 25.5 kDa (Figure 7) construct with 21 wt % CPT in one derivative 275 or a 15.4 kDa construct with 26 wt % CPT in another. 276 In ViVo studies with the high molecular weight polymer architectures showed an increase in activity compared to free CPT. Doses of 10 mg/kg of CPT, 21 mg/kg CPT equivalents in the polymer or 2.1 mg/kg CPT equivalents in the polymer afforded ∼90 day survival time.…”

Section: Sn-38 Liposomes (Le-sn-38) Animal Modelsmentioning

confidence: 96%

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Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

2010

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This review summarizes the in vivo assessment--preliminary, preclinical, and clinical--of chemotherapeutics derived from camptothecin or a derivative. Camptothecin is a naturally occurring, pentacyclic quinoline alkaloid that possesses high cytotoxic activity in a variety of cell lines. Major limitations of the drug, including poor solubility and inactivity at physiological conditions, prevent full clinical utilization. Camptothecin remains at equilibrium in an active lactone form and inactive hydrolyzed carboxylate form. The active lactone binds to DNA topoisomerase I cleavage complex, believed to be the single site of activity inhibiting DNA religation, resulting in apoptosis. A series of small molecule camptothecin derivatives have been developed that increase solubility, lactone stability and bioavailability to varying levels of success. A number of macromolecular agents have also been described wherein camptothecin(s) are covalently appended or non-covalently associated with the goal of improving solubility and lactone stability, while taking advantage of the tumor physiology to deliver larger doses of drug to the tumor with lower systemic toxicity. With the increasing interest in drug delivery and polymer therapeutics, additional constructs are anticipated. The goal of this review is to summarize the relevant literature for others interested in the field of camptothecin-based therapeutics, specifically in the context of biodistribution, dosing regimens, and pharmacokinetics with the desire of providing a useful source of comparative data. To this end, only constructs where in vivo data is available are reported. The review includes published reports in English through mid-2009.

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Section: Sn-38 Liposomes (Le-sn-38) Animal Modelsmentioning

confidence: 96%

“…276 In vivo studies with the high molecular weight polymer architectures showed an increase in activity compared to free CPT. Doses of 10 mg/kg of CPT, 21 mg/kg CPT equivalents in the polymer or 2.1 mg/kg CPT equivalents in the polymer afforded ~90 day survival time.…”

Section: Macromolecular Architectures For Passive Drug Deliverymentioning

confidence: 98%

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

2010

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“…If a drug molecule contains hydroxyl or amino groups, a polymeric drug is best prepared through the reaction of the drug with a presynthesized polymer with functional side groups able to react selectively with the aforementioned groups and produce ester or amido bonds 1, 3. Several activated esters and amides of acrylic acid, methacrylic acid, and their polymers have been described 4–9. In our previous work, we described the synthesis, polymerization, copolymerization, and exchange reactions of acrylic and methacrylic esters 10–16.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, exchange reactions, and biological activity of poly(8‐methacryloxyquinoline)

Khalil

2011

J of Applied Polymer Sci

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8-Methacryloxyquinoline (MAQ) was prepared through the reaction of 8-hydroxyquinoline with either methacryloyl chloride or methacrylic acid in the presence of triethylamine or N,N-dicyclohexylcarbodiimide, respectively. MAQ was polymerized in dimethylformamide with 2,2-azobisisobutyronitrile as the initiator. The reactions of the resulting polymers with hydroxyl and amino compounds were studied. The polymers were characterized with IR, 1 H-NMR, and mass spectroscopy.Some of the synthesized polymers were tested for their antimicrobial activity against bacteria and fungi. Generally, all the polymers were effective against the tested microorganisms, but their growth-inhibition effects varied.

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“…One promising approach for targetable drug delivery is the use of polymers. Recently, several activated polymers containing phthalimido moiety have been used as macromolecular drugs (Orzeszko et al , 2000; Lee et al , 2002, 2003; Lee and Theodorakis, 2003). One of the more interesting topics in the field of pharmacologically active polymers is the preparation of polymeric drugs in which drugs are attached to the polymeric backbone via covalent bonds with limited stability to biological environments (Ferruti and Vaccaroni, 2003; Ferruti et al , 1978).…”

Section: Introductionmentioning

confidence: 99%

Exchange reactions of poly‐2‐(N‐phthalimido)ethyl acrylate with hydroxy and amino compounds

Khalil

2005

Pigment &Amp; Resin Technology

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PurposeTo determine the optimal general condition for the synthesis and polymerisation of 2‐(N‐phthalimido)ethyl acrylate (NPEA), as well as the exchange reactions of poly‐NPEA with aminated and hydroxylated compounds as a model compound.Design/methodology/approachPreparation of 2‐(N‐phthalimido)ethyl acrylate by the reaction of N‐(2‐hydroxyethyl) phthalimide with acrylic acid and polymerisation of the resulting monomer. The exchange reactions of the resulting polymer with amines and hydroxy compounds were carried out. The structure of the resulting compounds were characterised.FindingsNPEA was prepared by the reaction of N‐(hydroxyethyl)phthalimide with acrylic acid. The monomer prepared was easily polymerised. The reactions of the resulting polymer with amines and hydroxy compounds were studied. In all cases, the exchange reactions were almost practically quantitative, which was confirmed by elemental analysis, IR and 1HNMR spectroscopy. Also, it was clear that poly‐NPEA showed a good behaviour as a model compound for a long active polymeric‐drug.Research limitations/implicationsThe new monomer described in the present investigation may be useful for the preparation of polymeric‐drug adducts. Also, similar monomeric phthalimides may be synthesised starting from a number of other hydroxy or amino acids, thus providing wider possibilities for the synthesis of pharmacologically active polymers.Practical implicationsThe method for preparation of monomer is simple and the exchange reactions provide a simple and practical solution to prepare some classes of macromolecular drugs.Originality/valueThe method of preparation of polymers was novel and may be useful for preparation of polymeric‐drug adducts.

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Synthesis and antitumour activity of medium molecular weight phthalimide polymers of camptothecin

Cited by 10 publications

References 23 publications

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

Synthesis, exchange reactions, and biological activity of poly(8‐methacryloxyquinoline)

Exchange reactions of poly‐2‐(N‐phthalimido)ethyl acrylate with hydroxy and amino compounds

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