Moisturizers: Function, Formulation and Clinical Applications

Chapter 14 Moisturizers: Function, Formulation and Clinical Applications




INTRODUCTION


Dermatologists are commonly queried by patients regarding proper care of their skin. Specific questions may include ‘What cleanser should I use?’ or ‘What is the best sunscreen?’ or ‘Is there a specific moisturizer that you recommend?’ It is common for practitioners to select from an array of samples, or to become familiar with a few brand name products through personal familiarity or the random experiences of individual patients. In the past, decisions regarding selection of skin care products were arbitrary; however, as more scientific information on skin care formulations continues to emerge, clinicians are basing their recommendations more frequently on the science behind the formulations.


A thorough understanding of the features of moisturizer formulations, and their differences, provides the clinician with a greater ability to recommend products appropriately and confidently. Various factors related to formulation science impact on the type and extent of clinical benefit achieved and the potential for unwanted effects (i.e. skin irritation, lack of esthetic appeal).


Two basic processes that function in concert to maintain the overall health of skin are cleansing and moisturizing. Cleansing allows for removal of external debris, natural cutaneous secretions, and microorganisms. Moisturizers are an important component of basic skin care, especially in conditions where clinical or subclinical alteration of the epidermal barrier and/or reduced epidermal water content is present. Such conditions include low ambient humidity and clinically evident xerosis due to genetic tendency (e.g. ichthyosis) or underlying disease states (e.g. atopic dermatitis, hypothyroidism, diabetes), or use of products or medications associated with epidermal barrier disruption such as harsh cleansers, astringents, and some topical medications. The myriad of moisturizer products available confounds rational product selection. The bottom line is to maintain a ‘simplest is best approach’, especially as many product claims, special additives, and carefully marketed ‘prestige products’ are backed by little or no scientific evidence supporting their benefit or extraordinary expense.


This chapter reviews the fundamental principles related to formulating various types of moisturizer formulation and the current understanding of skin barrier physiology and function. Specific components of moisturizers, their functions, and resultant clinical effects are discussed.



MAINTENANCE OF NORMAL SKIN INTEGRITY AND WATER CONTENT


Cutaneous water balance, homeostasis, and normal skin appearance require the presence of an intact epidermal barrier. The epidermal barrier is composed of two functioning components: (1) a cellular protein matrix composed of an intertwined and layered lattice of keratinocytes (‘bricks’) with an uppermost layer of thin stratum corneum cells (corneocytes), and (2) an intercellular lipid bilayer matrix (‘mortar’). Proper function and maintenance of both components assures skin integrity, water balance, hydration, and orderly corneocyte desquamation. Disturb-ance of either of the epidermal components produces increased transepidermal water loss (TEWL), resulting in xerotic skin changes, characterized by dryness, scaling, roughness, fine fissuring, and associated pruritus. The ideal range of stratum corneum water content is 20–35%; reduction to below 10% water content results in visibly evident xerotic skin changes.



• Role of corneocytes and natural moisturizing factor


The epidermis is in constant flux, as corneocytes traverse from below and ultimately desquamate. In the presence of adequate water content, desquamation occurs upon enzymatic degradation of desmosomes, allowing for separation and shedding of superficial corneocytes. Unlike normal skin, xerotic skin is characterized by retained corneodesmosomes within desquamating stratum corneum, resulting in shedding of ‘clumps’ of corneocytes visibly apparent as flakes or scales, as opposed to imperceptible desquamation of single corneocyte cells. Stratum corneum chymotryptic enzyme activity, integral to the hydrolysis of corneodesmosomes and the physiologic process of desquamation, is reduced in soap-induced dry skin as compared to normal skin.


The moisture content of corneocytes is maintained by small hygroscopic compounds which have been collectively categorized under the term ‘natural moisturizing factor’ (NMF). The components of NMF include filaggrin-derived amino acids, pyrrolidone carboxylic acid (PCA), lactate, sugars, and several electrolytes (Box 14.1). If stratum corneum water content falls below a critical level, enzymatic function required for normal desquamation is impaired, leading to corneocyte adhesion and accumulation of corneocytes on the cutaneous surface. These aberrant changes correspond with the visible appearance of dryness, roughness, scaling, flaking, chafing, and fissuring.




• Role of intercellular lipids


An important component of epidermal proliferation and differentiation is the formation of a permeability barrier composed of a programmed combination and ratio of lipids. Stratum corneum lipids are synthesized predominantly within the nucleated cells of the epidermis and are largely autonomous from circulating lipids. Lipid synthesis is regulated primarily by changes in epidermal barrier status. Epidermal barrier lipids are mostly composed of equimolar concentrations of free fatty acids, cholesterol, and ceramides. Lower quantities of cholesterol sulfate and nonpolar lipids are also present. The bipolar nature of lipids comprising the intercellular matrix allows for the formation of alternating lipid layers with hydrophilic ‘heads’ and hydrophobic ‘tails’. This orderly arrangement forms a barrier which controls water permeability and movement between epidermal cells (regulation of TEWL) and seals water-soluble hygroscopic compounds (NMF) within corneocytes, thus maintaining intracellular water content.


Epidermal lipids are also collected within lamellar bodies (Odland bodies) which are located within keratinocytes of the upper epidermis and function to biochemically convert newly synthesized lipids to an organized membrane structure (lamellar unit membrane structure). Lamellar bodies deliver proteolytic enzymes required for desquamation of corneocytes to the interstitium and convert ‘precursor lipids’ into vital barrier function lipids such as ceramides. As cornification occurs in the upper epidermis, a phospholipid-enriched plasma membrane is converted to a ceramide-rich bilayered membrane. At least seven subfractions of ceramides have been identified, accounting for up to 50% of stratum corneum lipid content by weight. Loss of epidermal lipids that are critical components of the lamellar epidermal barrier results in increased TEWL, a reduction in skin plasticity, and the adverse sequelae related to decreased stratum corneum water content as described above. Interestingly, significant reduction in multiple subfractions of ceramides has been noted in both lesional and nonlesional skin of patients with atopic dermatitis.




CLINICAL IMPACT OF MOISTURIZERS


In the presence of intrinsic or extrinsic factors that promote barrier disruption and reduced epidermal water content, moisturizers, especially those with optimized components, simulate the role of epidermal lipids in promoting and restoring epidermal barrier function. Externally applied lipids have been shown to intercalate between corneocytes and can mitigate surfactant-induced skin irritation. Application of nonphysiologic lipids such as petrolatum allows for restoration of barrier function by permeating within the interstitium of the stratum corneum and creating a diffuse hydrophobic phase.


Studies evaluating the application of physiologic lipids as moisturizers suggest that these lipids can be incorporated into the formation of barrier lipids and lamellar units and do not appear to downregulate physiologic lipid production in skin. However, based on in vitro murine models, the use of physiologic lipids in moisturizers appears to require the inclusion of all three lipid components (ceramide, cholesterol, free fatty acids) in optimized concentrations, otherwise barrier recovery may be impaired (Fig. 14.1).


Mar 12, 2016 | Posted by in General Surgery | Comments Off on Moisturizers: Function, Formulation and Clinical Applications

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