Pharmaceutical Manufacturing Handbook: Production and

478 LIPOSOMES AND DRUG DELIVERY
clinical, pharmaceutical, physical, chemical, biochemical, and toxicological sciences.
For ailment of eye diseases, topical administration is preferred over systemic in
order to avoid systemic toxicity, for rapid onset of action, and for decreasing the
required dose.
The main route for intraocular absorption is across the cornea [303] . In terms of
drug delivery, the cornea presents an effective barrier to the absorption of both
hydrophilic and lipophilic compounds. Actually, the main constraints in topical
ocular delivery are (i) poor ocular retention of conventional dosage forms [304] and
(ii) poor corneal absorption. Various approaches have been developed to increase
the bioavailability and duration of therapeutic action of ocular drugs. One such
approach is based on the use of drug delivery systems [305, 306] , which provide
controlled and continuous delivery of drugs and can also provide improved
(increased) residence time of the drug at the delivery site. Recently, intravitreal drug
injection has evolved into a preferred administration method for therapy of disorders
in the posterior segment of the eye [305] . The procedure is associated with a
high risk of complications, particularly when frequent, repeated injections are
required. Thus, sustained - release technologies are being proposed, and the benefi ts
of using colloidal carriers in intravitreal injections are currently under investigation
for posterior drug delivery.
Between the different types of particulate drug delivery systems, liposomes offer
additional advantages for ophthalmic delivery, since they are completely biodegradable
and relatively nontoxic and thus are well tolerated by the eye [305, 306] . Indeed,
when using other types of colloidal systems, for example , nanoparticles consisting
of polyalkyl cyanoacrylate, infl ammation and damage of the corneal epithelium
have been reported [307 – 309] . Another potential advantage of liposomes is their
ability to come in intimate contact with the corneal and conjunctival surfaces. This
results in increased probability of ocular drug absorption [310, 311] .
The potential of liposomes in topical ocular drug delivery was fi rst exploited in
the 1980s by a number of research groups [303, 310 – 315] . As an example, higher
levels of inulin were found in the cornea when it was encapsulated in liposomes as
compared to its aqueous solution [301, 314] , and this was attributed to the physical
adsorption of lipid vesicles onto the epithelial surface of the membrane [315, 316] .
More recently a number of liposomal applications for ocular delivery have been
under investigation [305, 306] for anterior as well as posterior segment administration,
as outlined in Table 3 . Indeed, a large number of ophthalmic drugs used in
cases of ocular surface disorders (such as dry eye syndrome) [317] , keratitis and
uveitis [318 – 327] , and keratoplasty [328 – 331] have been studied in liposomal form,
and in most cases the results were promising in terms of drug penetration and retention
in the various ocular tissues (cornea, sclera, retina, and choroids), following
subconjunctival administration. In some cases, detectable levels of drugs were found
in ocular tissues up to 7 days after administration [305, 306] .
As mentioned above, the ability to adsorb to the cornea and an optimal drug
release rate have been defi ned as the two liposomal attributes most responsible for
increasing bioavailability after topical ocular administration. A number of factors,
including drug encapsulation effi ciency, liposome size and charge, distribution of the
drug within liposomes, stability of liposomes in the conjunctival sac and ocular
tissues, their retention in the conjunctival sac, and most importantly their affi nity
toward the corneal surface and the rate of release of the encapsulated drug, have