Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems

Figures & data

Table 1. Biomaterials in enhanced transdermal drug delivery systems.

Classes	Examples	Application	Mechanisms	Ref.
PTD^a-drug complex	Polyarginine; TAT^b; YARA^c; SPACE^d	Topical; Topical and transdermal; Topical; Topical	Cell targeting; Co-delivery; Cellular penetration; Keratin Interaction	Rothbard et al. (2000); Lim et al. (2003); Lopes et al. (2005); Hsu & Mitragotri (2011)
Non-conjuagated peptides	Magainin; TD-1^e; T2^f; Non-conjugated PTD	Transdermal; Transdermal; Transdermal; Topical and Transdermal	Electrostatic effect; Pore forming; Lipid disruption; Cellular penetration	Kaushik (2001); Chen et al. (2006); Kumar et al. (2012); Hou et al. (2007)
Metabolic modulators	Lipid synthesis inhibitors; Trypsin	Transdermal; Transdermal	Reducing skin lipid amount; Altering keratin structure	Babita & Tiwary (2002); Li et al. (2008)
Chitosans	TMC^g LMWC^h N-Arg-CS^i	Transdermal Transdermal Transdermal	Keratin alteration; –; –	He et al. (2009); Sapra et al. (2008); Lv et al. (2011)
Cyclodextrins	HP-β-CD^j RAMEB^k 2,6-Diethyl-β-CD	Topical and transdermal; Topical and transdermal; Topical and transdermal	Solubility enhancement; SC lipid extraction; Drug release modifier	Zi et al. (2008); Legendre et al. (1995); Umemura et al. (1990);
Dendrimers	PAMAM Dendrimers PEGylated Dendrimers	Topical and transdermal Transdermal	Enhancing delivery in SC; Follicular penetration	Yang et al. (2012); Küchler et al. (2009)
Oligodimethylsiloxanes	GluO-ODMS^l	Transdermal	Lipid extraction	Akimoto et al. (2003)

^aProtein transduction domains; ^bHIV-1 transactivor of transcription (TAT) protein; ^csequence: YARAAARQARA; ^dsequence: AC-TGSTQHQ-CG; ^esequence: ACSSSPSKHCG; ^fsequence: LVGVFH; ^gN-trimethyl chitosan; ^hlow molecular weight chitosans; ⁱN-arginine chitosans; ^jhydroxypropyl-β-cyclodextrin; ^krandomly methylated β-CD. ^lGlucopiranosyl terminated oligodimethylsiloxanes.

Figure 1. Schematic representation of the skin delivery of PTD-drug complex. PTDs and drugs are conjugated via releasable or non-releasable chemical linker. In the body, the complex of PTD and cargo can exert its therapeutic effect after degradation into the free drug, or in the form of the conjugation with similar activity.

Figure 2. The formation of SC intercellular lipids that provide for the penetration barrier, adapted from Feingold (2007, 2009).

Figure 3. Schematic representation of generation (G) 4 dendrimers. In terms of molecular size, PAMAM dendrimers can be classified as G 0-10, and their surfaces can be modified to be amine-, carboxyl-, acetyl- or hydroxyl- terminated for different surface charge.

Figure 4. Schematic illustration of skin penetration of PAMAM dendrimers with different molecular size and surface attachments, SC: stratum corneum; VE: viable epidermis; DE: dermis, adapted from Yang et al. (2012).

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