Influence of peptide dendrimers and sonophoresis on the transdermal delivery of ketoprofen.
The aim of this study was to determine the individual and combined effects of peptide dendrimers and low frequency ultrasound on the transdermal permeation of ketoprofen. Arginine terminated peptide dendrimers of varying charges (4+, 8+and 16+, named as A4. A8 and A16 respectively) were synthesized and characterized. Ketoprofen was subjected to passive, peptide dendrimer-assisted and sonophoretic permeation studies (with and without dendrimer application) across Swiss albino mouse skin, both in vitro and in vivo. The studies revealed that the synthesized peptide dendrimers considerably increased the transdermal permeation of ketoprofen and displayed enhancement ratios of up to 3.25 (with A16 dendrimer), compared to passive diffusion of drug alone in vitro. Moreover, the combination of peptide dendrimer treatment and ultrasound application worked in synergy and gave enhancement ratios of up to 1369.15 (with ketoprofen-A16 dendrimer complex). In vivo studies demonstrated that dendrimer and ultrasound-assisted permeation of drug achieved much higher plasma concentration of drug, compared to passive diffusion. Comparison of transdermal and oral absorption studies revealed that transdermal administration of ketoprofen with A8 dendrimer showed comparable absorption and plasma drug levels with oral route. The excised mouse skin after in vivo permeation study with dendrimers and ultrasound did not show major toxic reactions. This study demonstrates that arginine terminated peptide dendrimers combined with sonophoresis can effectively improve the transdermal permeation of ketoprofen.
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka State, India.
Jyothsna
J
Manikkath
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka State, India.
Aswathi R
AR
Hegde
Department of Clinical Embryology, Kasturba Medical College, Manipal University, Manipal 576104, Karnataka State, India.
Guruprasad
G
Kalthur
School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE), The University of Queensland, Brisbane, QLD 4072, Australia.
Harendra S
HS
Parekh
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka State, India. Electronic address: ss.mutalik@manipal.edu.
Srinivas
S
Mutalik
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism; D050091:Dendrimers / Q000008:administration & dosage / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D007660:Ketoprofen / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D000069453:Ultrasonic Waves
D000894:Anti-Inflammatory Agents, Non-Steroidal; D050091:Dendrimers; D010446:Peptide Fragments; D007660:Ketoprofen
Ketoprofen; Peptide dendrimers; Sonophoresis; Transdermal; Ultrasound