Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies

Xiaoling Li; Nathan W. Adams; David B. Bennet; Jan Feijen; Sung Wan Kim

doi:10.1023/A:1015819715867

Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies

Xiaoling Li
, Nathan W. Adams
, David B. Bennet
, Jan Feijen
, Sung Wan Kim

Research output: Contribution to journal › Article › Academic › peer-review

7 Citations (Scopus)

Abstract

Prazosin, an antihypertensive drug with postsynaptic α1-aradrenergic blocking activity, has been coupled to poly-N 5-(3-hydroxypropyl-L-glutamine) (PHPG) via a carbamate linkage. PHPG was activated by p-nitrophenyl chloroformate and then reacted with prazosin to form p(HPG-prazosin carbamate) conjugate. Drug loading was 23.9% (w/w). Activated polymer and conjugates were characterized by infrared spectroscopy and differential scanning calorimetry. In vitro studies proceeded in pH 7.4 isotonic phosphate-buffered saline solution. Prazosin was released at a rate of 0.92 mg/day/100 mg conjugate from p(HPG-prazosin carbamate) particles. In vivo studies were performed with New Zealand White rabbits. P(HPG-prazosin carbamate) conjugate particles (100 mg) were suspended in 2 ml saline and injected subcutaneously into both flanks of rabbits. P(HPG-prazosin carbamate) conjugates, following an initial burst, demonstrated a nearly constant plasma prazosin concentration profile above 2 ng/ml, which was maintained for 10 days.

Original language	English
Pages (from-to)	527-530
Number of pages	4
Journal	Pharmaceutical research
Volume	8
Issue number	4
DOIs	https://doi.org/10.1023/A:1015819715867
Publication status	Published - 1991

Keywords

n/a OA procedure

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10.1023/A:1015819715867

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title = "Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies",

abstract = "Prazosin, an antihypertensive drug with postsynaptic α1-aradrenergic blocking activity, has been coupled to poly-N 5-(3-hydroxypropyl-L-glutamine) (PHPG) via a carbamate linkage. PHPG was activated by p-nitrophenyl chloroformate and then reacted with prazosin to form p(HPG-prazosin carbamate) conjugate. Drug loading was 23.9\% (w/w). Activated polymer and conjugates were characterized by infrared spectroscopy and differential scanning calorimetry. In vitro studies proceeded in pH 7.4 isotonic phosphate-buffered saline solution. Prazosin was released at a rate of 0.92 mg/day/100 mg conjugate from p(HPG-prazosin carbamate) particles. In vivo studies were performed with New Zealand White rabbits. P(HPG-prazosin carbamate) conjugate particles (100 mg) were suspended in 2 ml saline and injected subcutaneously into both flanks of rabbits. P(HPG-prazosin carbamate) conjugates, following an initial burst, demonstrated a nearly constant plasma prazosin concentration profile above 2 ng/ml, which was maintained for 10 days.",

keywords = "n/a OA procedure",

author = "Xiaoling Li and Adams, \{Nathan W.\} and Bennet, \{David B.\} and Jan Feijen and Kim, \{Sung Wan\}",

year = "1991",

doi = "10.1023/A:1015819715867",

language = "English",

volume = "8",

pages = "527--530",

journal = "Pharmaceutical research",

issn = "0724-8741",

publisher = "Springer",

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TY - JOUR

T1 - Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies

AU - Li, Xiaoling

AU - Adams, Nathan W.

AU - Bennet, David B.

AU - Feijen, Jan

AU - Kim, Sung Wan

PY - 1991

Y1 - 1991

N2 - Prazosin, an antihypertensive drug with postsynaptic α1-aradrenergic blocking activity, has been coupled to poly-N 5-(3-hydroxypropyl-L-glutamine) (PHPG) via a carbamate linkage. PHPG was activated by p-nitrophenyl chloroformate and then reacted with prazosin to form p(HPG-prazosin carbamate) conjugate. Drug loading was 23.9% (w/w). Activated polymer and conjugates were characterized by infrared spectroscopy and differential scanning calorimetry. In vitro studies proceeded in pH 7.4 isotonic phosphate-buffered saline solution. Prazosin was released at a rate of 0.92 mg/day/100 mg conjugate from p(HPG-prazosin carbamate) particles. In vivo studies were performed with New Zealand White rabbits. P(HPG-prazosin carbamate) conjugate particles (100 mg) were suspended in 2 ml saline and injected subcutaneously into both flanks of rabbits. P(HPG-prazosin carbamate) conjugates, following an initial burst, demonstrated a nearly constant plasma prazosin concentration profile above 2 ng/ml, which was maintained for 10 days.

AB - Prazosin, an antihypertensive drug with postsynaptic α1-aradrenergic blocking activity, has been coupled to poly-N 5-(3-hydroxypropyl-L-glutamine) (PHPG) via a carbamate linkage. PHPG was activated by p-nitrophenyl chloroformate and then reacted with prazosin to form p(HPG-prazosin carbamate) conjugate. Drug loading was 23.9% (w/w). Activated polymer and conjugates were characterized by infrared spectroscopy and differential scanning calorimetry. In vitro studies proceeded in pH 7.4 isotonic phosphate-buffered saline solution. Prazosin was released at a rate of 0.92 mg/day/100 mg conjugate from p(HPG-prazosin carbamate) particles. In vivo studies were performed with New Zealand White rabbits. P(HPG-prazosin carbamate) conjugate particles (100 mg) were suspended in 2 ml saline and injected subcutaneously into both flanks of rabbits. P(HPG-prazosin carbamate) conjugates, following an initial burst, demonstrated a nearly constant plasma prazosin concentration profile above 2 ng/ml, which was maintained for 10 days.

KW - n/a OA procedure

U2 - 10.1023/A:1015819715867

DO - 10.1023/A:1015819715867

M3 - Article

SN - 0724-8741

VL - 8

SP - 527

EP - 530

JO - Pharmaceutical research

JF - Pharmaceutical research

IS - 4

ER -

Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies

Abstract

Keywords

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