Actinic Kerarosis (AK) are hyperqueratotic cutaneous lesions, in
which an abnormal proliferation of keratinocytes of the epidermis is
present [1]. Since 1960s, topical 5-Fluorouracil (5-FU), a hydrophilic
antimetabolite drug, has been widely used as an effective treatment for
many pre-cancerous conditions and certain malignant tumors. However, the
severe inflammatory reaction, clinically characterized by erosion and
ulceration, which occurs in the skin following topical therapy, is still
a major treatment disadvantage. Topical delivery of hydrophilic drugs
through intact skin usually creates problems due to the inability of the
drugs to penetrate into stratum corneum. Liposomal formulations have
demonstrated capacity to increase penetration across and into skin of
these drugs when compared to conventional formulations [2]. Besides,
when applied on the stripped skin, in absence of barrier for drug
permeation, liposomes were found to provide targeted and sustained
topical delivery [3]. Thus, we hypothesized that liposomal formulation
containing entrapped 5-FU could be an interesting alternative for
topical treatment of AK. 5-FU encapsulation efficiency (EE) and
retention in liposomes are usually low (EE less than 10%). 5-FU does not
associate with the lipid bilayer [4] and EE depends mainly on the
internal aqueous volume of vesicles [5]. Therefore, EE has been greater
in large unilamellar vesicles (LUV) when compared to multilamellar
vesicles (MLV) and the physical state of the bilayer determines the
retention capacity of the vesicles [6]. Recently, MLV liposomes
containing 5-FU were prepared with high EE, but with an average vesicle
diameter of 5 m [7].