INTRODUCTION
Current topical treatments for acne include topical
retinoids such as tretinoin, antimicrobials such as
clindamycin, erythromycin, and benzoyl peroxide (BP),
and combination products. Recent advances in vehicle technologies,
not only allow for delivery of active ingredients with
improved efficacy and tolerability, but also offer added benefits
such as reduction in oiliness and facial shine.1-3 In particular,
topical drug therapy formulations using controlled-release microsphere
delivery systems (MDS) have been shown to absorb
facial oil.4,5 Considering that acne is a complex condition characterized
by excessive sebum production from the sebaceous
follicle6,7 and associated oiliness and facial shine,6,8-11 addressing
oil-related concerns among acne sufferers may prove to
increase patient satisfaction with treatment.8,12
Use of the Microsphere Delivery System in Dermatology
The MDS uses patented polymeric microspheres that are designed
to release active ingredient slowly over time.4,13 The
microspheres are formed by polymeric cross-linking, with multiple
interconnecting spaces. These porous microspheres are
loaded with the drug by diffusion, acting similarly to a sponge,
and are able to entrap a wide range of active ingredients such
as emollients, essential oils, and sunscreens.13 While resembling
a sponge in structure and function, the microspheres are
rigid and virtually noncompressible due to the high amount of
cross-linking in the polymeric structure.5
The macroporous beads, typically measuring 10-25 μm in diameter,
release active ingredient over time in response to stimuli
like physical manipulation when rubbed into the skin (pressure)
or a change in pH or temperature.4 The rate of release of active
ingredient also may be affected by factors such as the extent
of polymer cross-linking of the MDS (with more extensive cross-linking yielding a slower release rate), pore volume, and
microsphere particle size.4,13 Considering that the microspheres
themselves are too large to permeate the stratum corneum
and the active ingredient is not available until it leaves the
microsphere, there is lower accumulation of the drug at the
epidermis.4 This gradual release rate extends the duration of
beneficial effects of the active ingredient while minimizing cutaneous
irritation; the particles can reside on the surface of the
skin, thereby delivering active ingredient for a prolonged period
of time.4 Parameters of the MDS, such as particle size, pore
volume, diameter, and release characteristics, can be customized
to meet the needs of a specific therapeutic agent.5,13
The MDS technology is found across many dermatologic applications,
including for treatment of actinic keratoses or solar
keratoses, skin depigmentation, and acne. Carac® 5-fluorouracil
(5-FU) cream (Dermik; Bridgewater, NJ) utilizes 0.5% 5-FU in a
0.35% patented porous MDS for treating actinic keratosis or solar
keratoses of the face or anterior scalp.14 This formulation was
shown to reduce the irritation associated with administration of
5-FU.15 A combination of hydroquinone and retinol (EpiQuin Micro®; SkinMedica, Inc., Carlsbad, CA) is entrapped in an MDS for
delivering these active agents together in a controlled-release
manner for skin brightening.16 Oil-free mattifying agents also
have employed MDS technology to absorb excess surface oils
on the skin (eg, over-the-counter brands such as Dermalogica®
Oil Control Lotion, which utilizes a vinyl dimethicone/methicon
silsesquioxane cross-polymer MDS17).
For treating acne vulgaris, tretinoin microsphere gel 0.1% and
0.04% (Retin A Micro®; Valeant Dermatology, Bridgewater, NJ)
is encapsulated in a patented methyl methacrylate/glycol dimethacrylate
cross-polymer MDS in an aqueous gel.18 As well
as reducing the potential for skin irritation with tretinoin, the
