Review : Biodegradation of Drug-Modified Polymers in Drug Delivery- A Critical Analysis

Goddard, Peter; Petrak, Karel

doi:10.1177/088391158900400405

Cited by 12 publications

(3 citation statements)

References 48 publications

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“…20 The degradation products of macromolecular carriers by lyso-somal enzymes after endocytosis may be too large to diffuse out of the lysosomal compartment. 19,21 Conjugation of polymeric carriers with bioactive agents including targeting moieties may further change their degradation pattern and consequently their clinical usefulness.…”

Section: Introductionmentioning

confidence: 99%

Lysosomal degradability of poly(?-amino acids)

Chiu

Kopečková

Deshmane

et al. 1997

J. Biomed. Mater. Res.

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The lysosomal degradability of poly(alpha-amino acids) based on poly(L-glutamic acid) and its derivatives/copolymers was evaluated to gain insight into the subcellular fate of the macromolecules as water soluble polymeric drug carriers. The results indicate that both the incorporation of hydrophobic comonomers and modification of the carboxylic groups of glutamic acid side chains with hydroxyalkylamine increase the lysosomal degradability of the copolymers. Decreased lysosomal degradability of L-glutamic acid copolymers containing tripeptides terminated in p-nitroanilide (drug model) in the side chains confirmed that drug conjugation alters the degradation pattern of the polymeric carriers. The percentages of the enzymatic release of p-nitroaniline from its polymeric complex with time is relatively independent of the contents of the tripeptidyl p-nitroanilides attached to the polymeric conjugates. Determination of the degradation products by electrospray mass spectroscopy showed that no fragments less than 10(3) D were generated by lysosomal enzymes, whereas the main degradation products by papain and chymotrypsin were tripeptides and tetrapeptides. The conclusions derived from these data strongly suggest that these macromolecules, if used as lysosomotropic drug carriers, may accumulate in the lysosomes and limit their usefulness in some applications.

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Section: Introductionmentioning

confidence: 99%

Lysosomal degradability of poly(?-amino acids)

Chiu

Kopečková

Deshmane

et al. 1997

J. Biomed. Mater. Res.

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“…It was abundantly documented that these amphiphilic copolymers have tremendous advantages over other systems for incorporating therapeutic drugs through covalent bonding, 7,10,22 as well as physical entrapping, 3,12 to prolong blood circulation of the agents. The strategy employing these block copolymers was to incorporate bioactive molecules in the core of micellar colloid systems by forming self-assembling superstructures that otherwise would be insoluble or sparingly soluble in the aqueous medium.…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of enalapril maleate–loaded nanoparticles using amphiphilic diblock copolymers

Yoo¹,

Kim²,

Kim³

1999

J. Appl. Polym. Sci.

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Nanoparticles with the dimensions of circa 50 nm prepared from the micellar aggregation of diblock copolymers of poly(ethylene oxide) and polycaprolactone (PEO-b-PCL) were explored as a parenteral carrier system for water-soluble organic drugs in salt form. Enalapril maleate (EPM), developed for hypertension and congestive heart failure, was used as a model drug. The nanoparticles from three block copolymers with compositions of 5k-7.5k, 5k-5k, and 5k-2.5k (PEO-b-PCL) exhibited drugloading efficiency of 38%, 47%, and 26%, respectively, for an equivalent amount of EPM in a 1% (w/v) micelle solution. Particularly, 5k-5k micelles could be incorporated with the model drug up to 47% (w/w) of polymer. Furthermore, these nanoparticles possess drug-retaining capability at 25°C or below even after free EPM was eliminated from the aqueous phase by dialysis. A temperature-responsive release behavior was displayed upon heating to the physiological temperature, 37°C. Drug release from the micelles proceeded in a fairly linear fashion for a duration of about 4 -7 days, depending on the composition of the block copolymers. Daily average fractional release was consistent regardless of drug contents in the nanoparticles. In a preliminary animal toxicity test the EPM-loaded micelle solutions were intravenously administered to mice of the ICR strain through the tail vein. The animal subjects received 0.7 mL of EPM micelle solution up to six times and showed normal weight gain and food consumption.

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Section: Introductionmentioning

confidence: 99%