화장품에서 약물전달 기술의 응용에 관한 동향 및 최신기술 리뷰

조희경(Heui-Kyoung Cho),홍우진(Woo-Jin Hong),한현탁(Hyun-Tak Han) 한국화장품미용학회 2016 한국화장품미용학회지 Vol.6 No.2

Recently a variety of drug delivery system (DDS) have been explored and some of them are clinically used to deliver therapeutic drugs through skin. In topical delivery, the polymer based DDS as drug carrier should guarantee non-toxicity, long-term stability, and permeation efficacy for drugs, etc. For the development of the successful topical delivery system, it is of importance to develop the polymeric vehicles of well-defined intrinsic properties, such as molecular weights, HLB, chemical composition, topology, specific ligand conjugation and to investigate the effects of the properties on drug permeation behavior. In addition, the role of polymeric vehicles must be elucidated in in vitro and in vivo analyses. This article describes a kinds of theories and studies for skin permeation and some important features of polymer based DDS in topical delivery. Even though the application span of polymers has been truly broad in the cosmetic and pharmaceutical fields.

In Vitro and In Vivo Studies of Topical Delivery System of Gentisic Acid in Hairless Mice

Bian, ShengJie,Zheng, JunMin,Kim, Jung-Sun,Choi, Myeong Jun,Chung, Ho-Kwon,Lee, Chi-Ho,Kim, Dae-Duk 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3

Gentisic acid is a skin-whitening agent which inhibits the tyrosinase activity, an essential enzyme in the process of biological synthesis of melanin. Since melanin is synthesized in melanocytes located between the viable epidermis and dermis layer, drug amount delivered into the epidermis/dermis layer can provide valuable information for the biological effect of skin-whitening agents. The purpose of this study was to prepare the gentisic acid patches with 2% dodecylamine as enhancer, and to observe the in vitro skin permeation and in vivo skin deposition of gentisic acid. Gentisic acid in Duro-Tak 87-2510 patch formulation permeated across hairless mouse skin at the rate of 40.79㎍/㎠/hr. In vivo study showed that the gentisic acid amount in both the stratum corneum and the viable epidermis/dermis increased with the increase of application time. The amount of gentisic acid in the stratum corneum was higher than that in the epidermis/dermis layer, and was expected to provide a reservoir effect even after removing the patches. Thus, the patch formulation seems to be useful for the topical delivery of ski-whitening agent into the epidermis/dermis layer, the target site.

Polymeric vehicles for topical delivery and related analytical methods

Cho, Heui Kyoung,Cho, Jin Hun,Jeong, Seong Hoon,Cho, Dong Chul,Yeum, Jeong Hyun,Cheong, In Woo 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.4

Recently a variety of polymeric vehicles, such as micelles, nanoparticles, and polymersomes, have been explored and some of them are clinically used to deliver therapeutic drugs through skin. In topical delivery, the polymeric vehicles as drug carrier should guarantee non-toxicity, long-term stability, and permeation efficacy for drugs, etc. For the development of the successful topical delivery system, it is of importance to develop the polymeric vehicles of well-defined intrinsic properties, such as molecular weights, HLB, chemical composition, topology, specific ligand conjugation and to investigate the effects of the properties on drug permeation behavior. In addition, the role of polymeric vehicles must be elucidated in in vitro and in vivo analyses. This article describes some important features of polymeric vehicles and corresponding analytical methods in topical delivery even though the application span of polymers has been truly broad in the pharmaceutical fields.

Preparation and <i>in vivo</i> evaluation of cationic elastic liposomes comprising highly skin-permeable growth factors combined with hyaluronic acid for enhanced diabetic wound-healing therapy

Choi, Jeong Uk,Lee, Seong Wook,Pangeni, Rudra,Byun, Youngro,Yoon, In-Soo,Park, Jin Woo Elsevier Science B.V. Amsterdam 2017 ACTA BIOMATERIALIA Vol. No.

<P><B>Abstract</B></P> <P>To enhance the therapeutic effects of exogenous administration of growth factors (GFs) in the treatment of chronic wounds, we constructed GF combinations of highly skin-permeable epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor-A (PDGF-A). We genetically conjugated a low-molecular-weight protamine (LMWP) to the N-termini of these GFs to form LMWP-EGF, LMWP-IGF-I, and LMWP-PDGF-A. Subsequently, these molecules were complexed with hyaluronic acid (HA). Combinations of native or LMWP-fused GFs significantly promoted fibroblast proliferation and the synthesis of procollagen, with a magnification of these results observed after the GFs were complexed with HA. The optimal proportions of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and HA were 1, 1, 0.02, and 200, respectively. After confirming the presence of a synergistic effect, we incorporated the LMWP-fused GFs-HA complex into cationic elastic liposomes (ELs) of 107±0.757nm in diameter and a zeta potential of 56.5±1.13mV. The LMWP-fused GFs had significantly improved skin permeation compared with native GFs. The <I>in vitro</I> wound recovery rate of the LMWP-fused GFs-HA complex was 23% higher than that of cationic ELs composed of LMWP-fused GFs alone. Moreover, the cationic ELs containing the LMWP-fused GFs-HA complex significantly accelerated the wound closure rate in a diabetic mouse model and the wound size was maximally decreased by 65% and 58% compared to cationic ELs loaded with vehicle or native GFs-HA complex, respectively. Thus, topical treatment with cationic ELs loaded with the LMWP-fused GFs-HA complex synergistically enhanced the healing of chronic wounds, exerting both rapid and prolonged effects.</P> <P><B>Statement of Significance</B></P> <P>We believe that our study makes a significant contribution to the literature, because it demonstrated the potential application of cationic elastic liposomes as topical delivery systems for growth factors (GFs) that have certain limitations in their therapeutic effects (e.g., low percutaneous absorption of GFs at the lesion site and the requirement for various GFs at different healing stages). Topical treatment with cationic elastic liposomes loaded with highly skin-permeable low-molecular-weight protamine (LMWP)-fused GFs-hyaluronic acid (HA) complex synergistically enhanced the healing of diabetic wounds, exerting both rapid and prolonged effects.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

PROTECTIVE AND RETENTIVE EFFECTS OF LIPOSOMES ON WATER-DEGRADABLE HYDROCORTISONE ACETATE IN DERMATOLOGICAL APPLICATIONS

Bae, Soo Kyoung,KIm, Jin-Chul,Jee, Ung Kil,Kim, Jong-Duk 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-

Vanous dermatiological samples containing liposomes as a drug carrier were prepared, and the effects of variations in the dermatiological formulations, such as liposomal encapsulation, base materials, and the purity of lipid products, on drug stability and cbaracteristics for effective topical drug delivery were investigated. Hydrocortisone-21-acetate, a hydrophobic and water-degradable, anti-inflammatory agent, was used as the model drug. It was found that the liposomally encapsulated drug was more stable than the free-from drug in an ointment formulation. Also, the hydrogel base was found to be effective in maintaining drug stability in spite of its high water content. Another evidence tat liposomes were surrounding drug particles in the base was obtained from an in vitro test of drug permeation from liposome-hydrogel through the pig ear skin. the permeability of hydrocortisone acetate through the skin membrane was found to be 2 7-fold lower in the case of liposome-hydrogel than in the case of free-drug hydrogel. The results also suggested that liposomes play a role in localizing drug molecules in the skin membrane

A microemulsion-based hydrogel formulation containing voriconazole for topical skin delivery

김요한,김대덕,송정길,정은재,김동환 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.7

Microemulsion-based hydrogels (MBHs) containingvoriconazole were prepared as a possible topicaldelivery system for enhancing drug absorption at the site ofaction, as well as reducing the frequency of systemic sideeffects. Microemulsions were prepared with N-methyl-2-pyrrolidone as a surfactant, benzyl alcohol as an oil, and anethanol/phosphatidylcholine mixture (3:2, w/w) as acosurfactant. MBHs were prepared by adding carbopol 940or xanthan gum as a gelling agent. In vitro skin permeationand deposition studies were performed using static verticaldiffusion Franz cells and hairless mouse skin. The in vitropermeation data showed that the optimized microemulsionformulations consisting of voriconazole (1 %, w/w) andbenzyl alcohol (10 %, w/w) showed significantly higherdrug permeation rates and skin deposition compared topropylene glycol (control). However, the addition of agelling agent did not significantly change the permeationprofiles compared to the microemulsions. In vivo skindeposition studies conducted on hairless mice with MBHsalso confirmed the superiority of MBHs compared to thecontrol. These results suggested the MBH system to be apromising vehicle for topical delivery of voriconazole.

Polymeric vehicles for topical delivery and related analytical methods

조희영,조진훈,정성훈,조동철,염정현,정인우 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.4

Recently a variety of polymeric vehicles, suchas micelles, nanoparticles, and polymersomes, have beenexplored and some of them are clinically used to delivertherapeutic drugs through skin. In topical delivery, thepolymeric vehicles as drug carrier should guarantee nontoxicity,long-term stability, and permeation efficacy fordrugs, etc. For the development of the successful topicaldelivery system, it is of importance to develop the polymericvehicles of well-defined intrinsic properties, such asmolecular weights, HLB, chemical composition, topology,specific ligand conjugation and to investigate the effects ofthe properties on drug permeation behavior. In addition, therole of polymeric vehicles must be elucidated in in vitroand in vivo analyses. This article describes some importantfeatures of polymeric vehicles and corresponding analyticalmethods in topical delivery even though the applicationspan of polymers has been truly broad in the pharmaceutical fields.

Recombinant Human Epidermal Growth Factor (rhEGF)-loaded Solid Lipid Nanoparticles: Fabrication and Their Skin Accumulation Properties for Topical rhEGF Delivery

Hwang, Hee-Jin,Han, Sunhui,Jeon, Sangok,Seo, Joeun,Oh, Dongho,Cho, Seong-Wan,Choi, Young Wook,Lee, Sangkil Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.8

For the present study, rhEGF was encapsulated into solid lipid nanoparticles (SLNs). The SLNs were prepared by the $W_1/O/W_2$ double emulsification method combined with the high pressure homogenization method and the physical properties such as particle size, zeta-potential and encapsulation efficiency were measured. The overall particle morphology of SLNs was investigated using a transmission electron microscopy (TEM). The percutaneous skin permeation and accumulation property of rhEGF was evaluated using Franz diffusion cell system along with confocal laser scanning microscopy (CLSM). The mean particle size of rhEGF-loaded SLNs was $104.00{\pm}3.99nm$ and the zeta-potential value was in the range of -$36.99{\pm}0.54mV$, providing a good colloidal stability. The TEM image revealed a spherical shape of SLNs about 100 nm and the encapsulation efficiency was $18.47{\pm}0.22%$. The skin accumulation of rhEGF was enhanced by SLNs. CLSM image analysis provided that the rhEGF rat skin accumulation is facilitated by an entry of SLNs through the pores of skin.

Recombinant Human Epidermal Growth Factor (rhEGF)-loaded Solid Lipid Nanoparticles: Fabrication and Their Skin Accumulation Properties for Topical rhEGF Delivery

황희진,Sunhui Han,전상옥,서조은,Dong-Ho Oh,Seong-Wan Cho,최영욱,이상길 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.8

For the present study, rhEGF was encapsulated into solid lipid nanoparticles (SLNs). The SLNs were prepared by the W1/O/W2 double emulsification method combined with the high pressure homogenization method and the physical properties such as particle size, zeta-potential and encapsulation efficiency were measured. The overall particle morphology of SLNs was investigated using a transmission electron microscopy (TEM). The percutaneous skin permeation and accumulation property of rhEGF was evaluated using Franz diffusion cell system along with confocal laser scanning microscopy (CLSM). The mean particle size of rhEGF-loaded SLNs was 104.00 ± 3.99 nm and the zeta-potential value was in the range of −36.99 ± 0.54 mV, providing a good colloidal stability. The TEM image revealed a spherical shape of SLNs about 100 nm and the encapsulation efficiency was 18.47 ± 0.22%. The skin accumulation of rhEGF was enhanced by SLNs. CLSM image analysis provided that the rhEGF rat skin accumulation is facilitated by an entry of SLNs through the pores of skin.

Formulation consideration and skin retention study of microemulsion containing tazarotene for targeted therapy of acne

Mrunali R. Patel,Rashmin B. Patel,Jolly R. Parikh,Bharat G. Patel 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.1

The objective of this study was to develop and evaluate a novel microemulsion (ME) formulation containing tazarotene for targeted topical therapy of acne. Microemulsions (MEs) were formulated by spontaneous microemulsification method using 12 % Isopropyl myristate, mixed emulsifiers 15 % Labrasol-Cremophor-RH 40 (1:1), 15 % Capmul MCM and 58 % water (w/w) as an external phase. All plain and tazarotene loaded MEs were clear and showed physicochemical parameters for desired topical delivery and stability. The permeation profile of tazarotene through rat skin from selected ME formulation exhibited highest skin uptake. The microscopic observations indicated that the optimized ME had no significant effect on the microscopic structure of the skin and epithelial cells appeared mostly unchanged. The surface epithelium lining and the granular cellular structure of the skin were totally intact. The developed ME may be a potential drug delivery vehicle for targeted topical delivery of tazarotene in the treatment of acne.