Dexamethasone - PAMAM dendrimer conjugates for retinal delivery: preparation, characterization and in vivo evaluation.
OBJECTIVE
Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their treatment is still a challenge due to the special structure of the eye. The purpose of this study was to prepare a sustained release DEX conjugate formulation with enhanced ocular permeation using poly(amidoamine) (PAMAM) dendrimers and to evaluate the effects of conjugation on DEX release and ocular residence time.


METHODS
PAMAM G3.5 and PAMAM G4.5 dendrimers were used to prepare DEX conjugates, and conjugation was confirmed using (1) H-NMR. Formulations were evaluated in terms of drug release in the presence of ocular enzymes and cytotoxicity on ARPE19 cell lines. Fluorotron analysis was performed and ocular pharmacokinetic properties of DEX-PAMAM conjugates were studied in Sprague Dawley rats following intravitreal and subconjunctival applications.


RESULTS
The results indicated that DEX-PAMAM conjugates were able to enhance ocular permeability and ocular tissue levels of DEX following subconjunctival injection, and results were encouraging when compared to the literature that has reported DEX getting cleared from vitreous in 3 h.


CONCLUSIONS
Current studies are focused on formulation improvement to enhance hydrolysis and clearance time.
Pharmaceutical Technology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Burçin
http://orcid.org/0000-0003-2352-9321
B
Yavuz
Pharmaceutical Technology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Sibel
S
Bozdağ Pehlivan
Department of Chemistry, Boğaziçi University, Istanbul, Turkey.
Burcu
B
Sümer Bolu
Department of Chemistry, Boğaziçi University, Istanbul, Turkey.
Rana
R
Nomak Sanyal
Pharmaceutical Technology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
İmran
İ
Vural
Pharmaceutical Technology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Nurşen
N
Ünlü
D000818:Animals; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004333:Drug Administration Routes; D004337:Drug Carriers; D016503:Drug Delivery Systems; D065546:Drug Liberation; D008297:Male; D010539:Permeability; D017207:Rats, Sprague-Dawley; D012160:Retina; D012164:Retinal Diseases / Q000188:drug therapy
D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D003907:Dexamethasone
PAMAM dendrimers; controlled and sustained release systems; dosage form design and characterization; drug delivery to specific tissues; retinal drug delivery