# Somatotropin Penetration Testing from Formulations Applied Topically to the Skin
## 4 Discussion  
The transdermal delivery of therapeutic substances has many advantages over conventional paths of administration. However, the penetration of biological molecules through the skin layers is limited by their dimensions and characteristics. The enhancers of the transdermal delivery of therapeutic peptides and proteins are the subject of ongoing testing [38; 39]. While overcoming the living layers of the skin, peptide drugs can undergo enzymatic degradation [40; 41; 42]. However, as a consequence of quick uptake into the circulatory system after reaching the highly vascularized papillary skin zone, the metabolism of peptides/proteins most likely occurs while passing through the epidermal layer of the skin [43]. However, that route of administration appears favorable due to the prevention of enzymatic degradation in the digestive tract and liver. There are penetration enhancement techniques that can also affect enzyme activity, as described for ultrasound, which can contribute to the deactivation of certain skin enzymes [44; 45]. Encapsulation may provide some protection against skin enzymes, although the exact moment at which the drug leaves its \"protective capsule\" as it passes through the tissue has yet to be defined [38; 39]. There are many reports that ALB binds to the drug molecule and has a protective effect on it. Binding to plasma proteins prevents substances from being oxidized, decreases their toxicity and elongates their half-life, and drugs which are tightly associated with plasma proteins tend to have a low first-pass effect [46]. The biologically active glucagon-like peptide-1, GLP-1 (7-37), has a half-life of 1.5 to 2 min. Liraglutide is an ALB-bond form of GLP-1 and is modified with myristic acid. Unlike GLP-1, liraglutide is stable to metabolic degradation and has a plasma half-life of 11-15 h after subcutaneous administration, allowing it to be administered once daily [47]. When administered transdermally, ALB nanoparticles could, however, bypass the stratum corneum barrier for delivery through the hair follicle. Furthermore, the nanoparticles could be kept in the hair follicles for a sufficiently long period. This would allow systemic absorption and topical activity, and possibly provide a prolonged release effect [15; 48]. Hydrogels using cellulose derivatives as hormone carriers (testosterone, proges-terone, insulin, estradiol) are known to be used [49]. MC, sodium carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC) have been used to obtain hydrogels. The efficacy of using HPMC as a testosterone carrier was reported by [PERSON] et al. [50] In a study on designing a hydrogel matrix for insulin, [PERSON] et al. [51] studied the  
Figure 6: Shear stress values of the tested formulations after preparation (initially) and after 4 weeks of storage at different temperatures, measured at two different shear rates: (**a**) D = 15 s\({}^{-1}\); (**b**) D = 30 s\({}^{-1}\). usefulness of Carbopol Ultrez 10, Carbopol Ultrez 30, MC and glycerol hydrogel. They observed that the largest amount of insulin was released from the MC-based gel--75%. The hormone was released sequentially for up to nine hours. The MC hydrogel showed very favorable properties, enabling its spreadability on the skin [50]. [PERSON] et al. confirmed the effectiveness of MC in an ALB permeation test. The largest amount of ALB permeated via porcine skin from MC-based hydrogel--35.6 percent within 24 h. The use of MC with chitosan as a matrix for ALB reduced the amount of permeated ALB from the hydrogel by 1.7-fold; sodium alginate reduced it by 2.5-fold, while HPMC caused 3-fold less ALB to permeate [29]. [PERSON] et al. used chitosan and bovine serum ALB to prepare nanogels containing muiprocin (MPR). Both the ALB and the muclaginous ability of chitosan could prolong the duration of Col/hal NPs presence at the destination, favoring a longer drug release. However, to improve the chitosan gelation (adhesion) properties, Carbopol 940 had to be added at concentration 2% and 3%.