Pharmacokinetics and Pharmacodynamics of Sterylglucoside-Modified Liposomes for Levonorgestrel Delivery via Nasal Route

Abstract

For emergency contraceptive, the rapid delivery of levonorgestrel (LNG) to plasma is desirable, furthermore, a sustained delivery of LNG along with rapid absorption will be necessary. The pharmacokinetics and pharmacodynamics of LNG entrapped in different kinds of liposome formulations via nasal administration in rats were evaluated and compared with LNG suspension via the oral route. The relative bioavailabilities of these liposome formulations via nasal administration were 100% or higher than 100%. The C max and T max values of sterylglucoside (SG) and chitosancontained formulations by nasal administration were 416.84 ng/mL and 1.02 hr, 227.97 ng/mL and 2.02 hr, respectively, compared with that of 334.94 ng/mL and 1.89 hr of oral suspension. Fully 100% contraception was observed for all the formulations. SG could promote the absorption of LNG via the nasal route and may provide a rapid onset of action of LNG for emergency contraception. Chitosan could retain LNG in the nasal cavity for long contact time to sustain delivery of LNG. The rapid onset and sustained delivery of LNG can be achieved via the nasal route using liposomes as the vehicle.

Intranasal Drug Delivery: How, Why and What for?

“…Liposomes can be incorporated in different formulations. For example, Ding et al (48) obtained a rapid onset of action and sustained delivery of levonorgestrel when it was intranasally administered as a liposome suspension. Furthermore, positive results were also found during nasal delivery of acyclovir in a liposomal gel (64).…”

“…Consequently, the number of drugs administered as nasal formulations intended to achieve systemic effects has widely increased. Some prominent examples include analgesics (morphine) (4, 7, 51), cardiovascular drugs as propranolol (52) and carvedilol (53), hormones such as levonorgestrel (48), progesterone (54) and insulin (49,(55)(56)(57), anti-inflammatory agents as indomethacin (58, 59) and ketorolac (60, 61), and antiviral drugs (acyclovir) (62-65). Actually, there are some examples already available in the market (Table 2).…”

A Review on Nasal Drug Delivery System and Its Contribution in Therapeutic Management

“…Therapeutic classes of drugs delivered include analgesics (exmorphine), cardiovascular drugs as propranolol and carvedilol, hormones such as levonorgestrel, progesterone, and insulin, anti-inflammatory agents as indomethacin and ketorolac, and antiviral drugs (acyclovir). Some examples which are available in the market include zolmitriptan and sumatriptan for the treatment of a migraine and cluster headaches [9,[11][12][13][14][15].…”

Enhanced intranasal delivery of gemcitabine to the central nervous system

“…Examples of drugs administered as nasal formulations to achieve systemic effects include analgesics (morphine) (Illum 2003;Illum 2002;Stoker et al 2008); cardiovascular drugs such as carvedilol (Patil and Sawant 2009); hormones such as levonorgestrel (W.-X. Ding et al 2007), progesterone (Rathnam, Narayanan, and Ilavarasan 2008) and insulin (Varshosaz, Sadrai, and Heidari 2006;S. Yu et al 2004;Jian Wang, Tabata, and Morimoto 2006); anti-inflammatory agents such as indomethacin (Karasulu et al 2008;Onischuk et al 2008) and ketorolac (Leykin et al 2008;Moodie et al 2008); and antiviral drugs (acyclovir) (Shao et al 1994;Yang, Gao, and Mitra 2001;Alsarra, Hamed, and Alanazi 2008;Alsarra et al 2009).…”