Drug-Cyclodextrin-Vesicles Dual Carrier Approach for Skin Targeting of Anti-acne Agent

Abstract

Abstract. In the present study attempt was made for preparation of isotretinoin-hydroxypropyl β cyclodextrin (HP-β-CD) inclusion complex and encapsulate this complex in elastic liposomes to study the effect of dual carrier approach on skin targeting of isotretinoin. The isotretinoin HP-β-CD complex was prepared by freeze-drying method and characterized by IR spectroscopy. The drug and drug-CD complex loaded elastic liposomal formulation were prepared and characterized in vitro, ex-vivo and in vivo for shape, size, entrapment efficiency, no. of vesicles per cubic mm, in vitro skin permeation and deposition study, photodegradation and skin toxicity assay. The transdermal flux for different vesicular formulations was observed between 10.5±0.5 to 13.9±1.6 μg/cm 2 /h. This is about 15-21 folds higher than that obtained from drug solution (0.7 ±0.1 μg/cm 2 /h) and 4-5 folds higher than obtained with drug-CD complex solution (2.7±0.1 μg/cm 2 /h). The amount of drug deposit was found to increase significantly (p<0.05) by cyclodextrin complexation (30.1±0.1 μg). The encapsulation of this complex in elastic liposomal formulation further increases its skin deposition (262.2 ±21 μg). The results of skin irritation study using Draize test also showed the significant reduction in skin irritation potential of isotretinoin elastic liposomal formulation in comparison to free drug. The results of the present study demonstrated that isotretinoin elastic liposomal formulation possesses great potential for skin targeting, prolonging drug release, reduction of photodegradation, reducing skin irritation and improving topical delivery of isotretinoin.

(Phospho)lipid-based Nanosystems for Skin Administration

“…Moreover, the skin irritation study confirmed the significant reduction in irritation potential of isotretinoin elastic liposomal formulation in comparison to the free drug [170].…”

Localized delivery of paclitaxel using elastic liposomes: Formulation development and evaluation

“…Elastic liposomes are of several orders of magnitude more deformable than the standard liposomes, and thus well suited for skin penetration (Cevc et al, 1997;Jain et al, 2003). In our previous study, we have found higher skin permeation and deposition potential of elastic liposomes-based formulation of diclofenac , rizatriptan (Garg et al, 2008), colchicine (Singh et al, 2009), and isotretinoin (Kaur et al, 2010).…”

Cyclodextrin complexes: Perspective from drug delivery and formulation

“…Oral administration of chitosan/alginate/phospholipid in combination with β-CD was explored for brain targeting (Shan et al, 2016). Promising results were Clonazepam Me-β-CD Liposomal and microemulsion formulations contain drug-CD complex showed greater solubility and permeation Mura, Bragagni, Mennini, Cirri, and Maestrelli (2014) Curcumin HP-β-CD Increases solubility, transdermal permeation of curcumin, and demonstrated better anti-inflammatory effect Ghanghoria, Kesharwani, Agashe, and Jain (2013) Diclofenac sodium HP-β-CD HP-β-CD grafted polyethyleneimine has proved as a potent skin penetration enhancer with no toxicity or skin irritation Yan et al (2014) Epalrestat ME-β-CD Enhanced dissolution and skin permeation through hairless mouse skin Furuishi et al (2017) Flurbiprofen HP-β-CD Polymeric nanospheres with drug-CD complex showed greater retention of drug in skin as well as stronger anti-inflammatory effect Vega et al (2013) Isotretinoin HP-β-CD Elastic liposomes significantly increased the skin deposition, prolonged drug release and reduce skin irritation Kaur, Puri, and Jain (2010) Itraconazole HP-β-CD Deformable liposomes contain drug-CD complex showed greater cutaneous drug deposition Alomrani, Shazly, Amara, and Badran (2014) Levodopa β-CD Stability of levodopa was enhanced when complexed with β-CD in transdermal patches Obaidat, Al-Shar'i, Tashtoush, and Athamneh (2016) Lornoxicam HP-β-CD Incorporation of CD and propylene glycol in gel improved the skin permeation Al-Suwayeh, Taha, Al-Qahtani, Ahmed, and Badran (2014) Propofol SBE-β-CD Complexation significantly improved the passive and iontophoretic transdermal flux Juluri, Peddikotla, Repka, and Murthy (2013) Terbinafine HP-β-CD Demonstrated the potential of CD as a transungual permeation enhancer Chouhan and Saini (2014) shown after clinical trials of KLEPTOSE CRYSMEB and 2-HP-β-CDbased therapy as cholesterol-chelating agent in atherosclerosis and Niemann-Pick type C disease (Coisne et al, 2016). β-CD-based inclusion complexes for targeted drug delivery system incorporating aspirin (Ma et al, 2015) and diclofenac (Vieira et al, 2016) have been demonstrated.…”