Macromolecular prodrugsXI. Synthesis and characterization of polymer–estradiol conjugate

Zovko, Marijana; Zorc, Branka; Novak, Predrag; Tepeš, Predrag; Cetina-Čižmek, Biserka; Horvat, M

doi:10.1016/s0378-5173(04)00452-1

Cited by 6 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They can be prepared by ring-opening polymerization of the corresponding amino acid N -carboxy anhydrides, enabling the synthesis of polymers with controlled molecular weights and narrow distributions . Their conjugation with drugs − provides biodegradable drug conjugates that have been tested in the treatment of cancer. Conjugates of mitomycin C and N , N -di(2-chloroethyl)-4-phenylenediamine mustard bound via GFG or GFAG oligopeptide spacers to a poly[ N -5-(2-hydroxyethyl)- l -glutamine] (PHEG) carrier as well as similar conjugates with PEG side groups showed notable in vivo antitumor activity, inducing extended survival in animal models and lower side toxicity than the parent drugs.…”

Section: Synthetic Water-soluble Polymer–drug Conjugates For Cancer T...mentioning

confidence: 99%

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies

et al. 2016

View full text Add to dashboard Cite

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.

show abstract

Section: Synthetic Water-soluble Polymer–drug Conjugates For Cancer T...mentioning

confidence: 99%

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In the former, the molecule acts as a substrate for enzymes, which then release the active drug [ 4 , 5 ], whereas, in the latter, the parent drug is linked through enzymatically or chemically cleavable groups to a molecule that acts as a carrier [ 4 ]. The carrier can also be a polymer, and, in this case, they are known as macromolecular prodrugs [ 6 , 7 ]. Another class bears the name mutual prodrugs; here, two active compounds are linked, with each acting as a transporter of the other [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Galactosylated Prodrugs: A Strategy to Improve the Profile of Nonsteroidal Anti-Inflammatory Drugs

et al. 2022

View full text Add to dashboard Cite

Carbohydrates are one of the most abundant and important classes of biomolecules. The variety in their structures makes them valuable carriers that can improve the pharmaceutical phase, pharmacokinetics and pharmacodynamics of well-known drugs. D-galactose is a simple, naturally occurring monosaccharide sugar that has been extensively studied for use as a carrier and has proven to be valuable in this role. With the aim of validating the galactose-prodrug approach, we have investigated the galactosylated prodrugs ibuprofen, ketoprofen, flurbiprofen and indomethacin, which we have named IbuGAL, OkyGAL, FluGAL and IndoGAL, respectively. Their physicochemical profiles in terms of lipophilicity, solubility and chemical stability have been evaluated at different physiological pH values, as have human serum stability and serum protein binding. Ex vivo intestinal permeation experiments were performed to provide preliminary insights into the oral bioavailability of the galactosylated prodrugs. Finally, their anti-inflammatory, analgesic and ulcerogenic activities were investigated in vivo in mice after oral treatment. The present results, taken together with those of previous studies, undoubtedly validate the galactosylated prodrug strategy as a problem-solving technique that can overcome the disadvantages of NSAIDs.

show abstract

“…Poly[a,b-(N-2-hydroxyethyl-DL-aspartamide)]-poly[a,b-(N-2-aminoethyl-DL-aspartamide)] (PAHA) is a copolymer of polyaspartamide type that has been successfully applied in the synthesis of several macromolecular prodrugs, including 17b-estradiol-3-benzoate (9), diclofenac, fenoprofen (10) and broxuridine (11).…”

mentioning

confidence: 99%

Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymer

Končić¹,

Zorc²,

Novak³

2011

Acta Pharmaceutica

View full text Add to dashboard Cite

Polymer-drug conjugates are macromolecular drug carrier systems with active agents attached as side substituents to a polymer backbone using an appropriate spacer. They could be an effective way to prolong drug activity, minimize unfavorable side effects and toxicity, decrease the required dose and increase the solubility of drugs (1). In addition, polymer-drug conjugates have the ability to overpass some mechanisms of drug resistance and the potential to elicit immunostimulatory effects. They can also alter the body distribution of drugs and ensure adequate drug delivery to target cells or tissues. This is Two hydrosoluble conjugates of 17b-estradiol (ED) and estradiol-17b-valerate (EV) with polyaspartamide polymer were prepared and characterized. ED and EV were first chemically modified and bound to poly[a,b-(N-2-hydroxyethyl-DL-aspartamide)]-poly[a,b-(N-2-aminoethyl-DL-aspartamide)] (PAHA), a hydrosoluble polyaspartamide--type copolymer bearing both hydroxyl and amino groups. ED was first converted to 17-hemisuccinate (EDS) and then bound to PAHA. In the resulting conjugate PAHA-EDS, the estradiol moiety was linked to the polymer through a 2-aminoethylhemisuccinamide spacer. On the other hand, EV was first converted to estradiol-17b-valerate-3--(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EV. In the prepared conjugate PAHA-EV, the estradiol moiety was covalently bound to the polyaspartamide backbone by carbamate linkage, through an ethylenediamine spacer. The polymer-drug conjugates were designed and prepared with the aim to increase water--solubility, bioavailability and to improve drug delivery of the lipophilic estrogen hormone.

show abstract

Macromolecular prodrugsXI. Synthesis and characterization of polymer–estradiol conjugate

Cited by 6 publications

References 0 publications

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies

Galactosylated Prodrugs: A Strategy to Improve the Profile of Nonsteroidal Anti-Inflammatory Drugs

Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymer

Contact Info

Product

Resources

About