PMID- 20148292
OWN - NLM
STAT- MEDLINE
DCOM- 20100608
LR  - 20211020
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 27
IP  - 4
DP  - 2010 Apr
TI  - Formulation and in vitro-in vivo evaluation of black raspberry extract-loaded 
      PLGA/PLA injectable millicylindrical implants for sustained delivery of 
      chemopreventive anthocyanins.
PG  - 628-43
LID - 10.1007/s11095-009-0038-5 [doi]
AB  - PURPOSE: The objective of this study was to formulate and evaluate freeze-dried 
      black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic 
      acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants 
      for sustained delivery of chemopreventive FBR anthocyanins 
      (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and 
      cyanidin-3-rutinoside (CR)). METHODS: Identification and quantitation of CS, CG, 
      and CR in RE was performed by mass spectroscopy and HPLC. 
      RE:triacetyl-beta-cyclodextrin (TA-beta-CD) inclusion complex (IC) was prepared 
      by a kneading method and characterized by X-ray diffraction (XRD), nuclear 
      magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or 
      RE:TA-beta-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion 
      method. In vitro and in vivo controlled release studies were conducted in 
      phosphate-buffered saline Tween-80 (pH 7.4, 37 degrees C) and after subcutaneous 
      administration in male Sprague-Dawley rats, respectively. Anthocyanins were 
      quantified by HPLC at 520 nm. RESULTS: The content of CS, CG, and CR in RE was 
      0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in 
      solution was determined to be pH-dependent, and their degradation rate increased 
      with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded 
      with 5 or 10 wt% RE exhibited a high initial burst and short release duration of 
      anthocyanins (35-52 and 80-100% CG + CR release after 1 and 14 days, 
      respectively). The cause for rapid anthocyanins release was linked to higher 
      polymer water uptake and porosity associated with the high osmolytic components 
      of large non-anthocyanin fraction of RE. XRD, (1)H NMR and UV-visible 
      spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed 
      an IC with TA-beta-CD, decreasing the hydrophilicity of RE. Formation of an IC 
      with hydrophobic carrier, TA-beta-CD, provided better in vitro/in vivo sustained 
      release of FBR anthocyanins (16-24 and 97-99% CG + CR release, respectively, 
      after 1 and 28 days from 20 wt% RE:TA-beta-CD IC/PLA implants) over 1 month, 
      owing to reduced polymer water uptake and porosity. CONCLUSION: PLA injectable 
      millicylindrical implants loaded with RE:TA-beta-CD IC are optimal dosage forms 
      for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.
FAU - Desai, Kashappa Goud H
AU  - Desai KG
AD  - Department of Pharmaceutical Sciences, University of Michigan, 428 Church St., 
      Ann Arbor, MI, USA.
FAU - Olsen, Karl F
AU  - Olsen KF
FAU - Mallery, Susan R
AU  - Mallery SR
FAU - Stoner, Gary D
AU  - Stoner GD
FAU - Schwendeman, Steven P
AU  - Schwendeman SP
LA  - eng
GR  - R01 CA095901/CA/NCI NIH HHS/United States
GR  - R01 CA095901-03/CA/NCI NIH HHS/United States
GR  - R01 CA129609/CA/NCI NIH HHS/United States
GR  - R01 CA95901/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100211
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Anthocyanins)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Polyesters)
RN  - 0 (Polymers)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 459TN2L5F5 (poly(lactide))
SB  - IM
MH  - Animals
MH  - Anthocyanins/*administration & dosage/analysis/pharmacology/*therapeutic use
MH  - Antineoplastic Agents, Phytogenic/*administration & 
      dosage/analysis/pharmacology/*therapeutic use
MH  - Delayed-Action Preparations/*chemistry
MH  - Fruit/*chemistry
MH  - Injections
MH  - Lactic Acid/chemistry
MH  - Male
MH  - Polyesters
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers/chemistry
MH  - Prostheses and Implants
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rosaceae/*chemistry
PMC - PMC2880396
MID - NIHMS204826
EDAT- 2010/02/12 06:00
MHDA- 2010/06/09 06:00
PMCR- 2010/06/03
CRDT- 2010/02/12 06:00
PHST- 2009/08/18 00:00 [received]
PHST- 2009/12/14 00:00 [accepted]
PHST- 2010/02/12 06:00 [entrez]
PHST- 2010/02/12 06:00 [pubmed]
PHST- 2010/06/09 06:00 [medline]
PHST- 2010/06/03 00:00 [pmc-release]
AID - 10.1007/s11095-009-0038-5 [doi]
PST - ppublish
SO  - Pharm Res. 2010 Apr;27(4):628-43. doi: 10.1007/s11095-009-0038-5. Epub 2010 Feb 
      11.