長庚大學 藥劑學研究室 Pharmaceutics Laboratory, Chang Gung University

• Chiang, Y.R., Li, A., Leu, Y.L., Fang, J.Y., Lin, Y.K. (2013) An in vitro study of the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore. Molecules, 18, 14381-14396.
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• Hsieh, P.W., Chen, W.Y., Aljuffali, I.A., Chen, C.C., Fang, J.Y.* (2013) Co-drug strategy for promoting skin targeting and minimizing transdermal diffusion of hydroquinone and tranexamic acid. Curr. Med. Chem., 20, 4080-4092.
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• Chen, W.Y., Fang, C.L., Al-Suwayeh, S.A., Yang, H.H., Li, Y.C., Fang, J.Y.* (2013) Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing: optimization of the applied dose for postoperative care. Lasers Med. Sci., 28, 1363-1374.
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• Hsu, S.H., Wen, C.J., Al-Suwayeh, S.A., Huang, Y.J., Fang, J.Y.* (2013) Formulation design and evaluation of quantum dot-loaded nanostructured lipid carriers for integrating bioimaging and anticancer therapy. Nanomedicine, 8, 1253-1269.
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• Wen, C.J., Sung, C.T., Aljuffali, I.A., Huang, Y.J., Fang, J.Y.* (2013) Nanocomposite liposomes containing quantum dots and anticancer drugs for bioimaging and therapeutic delivery: a comparison of cationic, PEGylated, and deformable liposomes. Nanotechnology, 24, 325101.
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• Fang, J.Y., Wu, T.H., Huang, C.H., Wang, P.W., Chen, C.C., Wu, Y.C., Pan, T.L. (2013) Proteomics reveals plasma profiles for monitoring the toxicity caused by chromium compounds. Clin. Chim. Acta, 423, 23-31.
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• Lin, C.F., Hwang, T.L., Al-Suwayeh, S.A., Huang, Y.L., Hung, Y.Y., Fang, J.Y.* (2013) Maximizing dermal targeting and minimizing transdermal penetration by magnolol/honokiol methoxylation. Int. J. Pharm., 445, 153-162.
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• Lee, W.R., Shen, S.C., Al-Suwayeh, S.A., Yang, H.H., Li, Y.C., Fang, J.Y.* (2013) Skin permeation of small-molecule drugs, macromolecules, and nanoparticles mediated by a fractional carbon dioxide laser: the role of hair follicles. Pharm. Res., 30, 792-802.
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• Fang, J.Y., Liu, Y.T., Huang, Y.B., Pan, T.L., Wang, H.H., Hsieh, P.W. (2013) Pharmacokinetics, biodistribution, and toxicology following intravenous and oral administration of DSM-RX78 and EFB-1, two new 2-(2-fluorobenzamido)benzoate-based PDE4 inhibitors to rats. J. Pharm. Pharmacol., 65, 345-354.
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• Lin, Y.K., Al-Suwayeh, S.A., Leu, Y.L., Shen, F.M., Fang, J.Y.* (2013) Squalene-containing nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of diphencyprone for treating alopecia areata. Pharm. Res., 30, 435-446.
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• Fang, C.L., Al-Suwayeh, S.A., Fang, J.Y.* (2013) Nanostructured lipid carriers (NLCs) for drug delivery and targeting. Recent Pat. Nanotechnol., 7, 41-55.

實驗室主持人 Professor

方嘉佑 Jia-You Fang

博士後研究 Post Doc.

楊世駿 Shih-Chun Yang

林資展 Zih-Chan Lin

研究助理 Research Assistants

胡凱茵 Kai-Yin Hu

戴攸珊 You-Shan Dai

蕭裕泰 Yu-Tai Hsiao

洪嘉伶 Chia-Lin Hung

古珮渝 Pei-Yu Ku

陳恩立 En-Li Chen

劉珮瑩 Pei-Ying Liu

鍾采玲 Cai-Ling Jhong

陳韋彰 Wei-Chang Chen

博士班 Ph.D Candidates

林承諭 Chen-Yu Lin

G.R. Nirmal

碩士班 Graduate Students

魏榯誸 Shi-Hsien Wei

李玫樺 Mei-Hua Li

黃芷淇 Jhi-Chi Huang

簡旻瑜 Min-Yu Chien

林姿瑋 Chi-Wei Lin

張晏慈 Yen-Tzi Chang

許芷嘉 Chi-Chia Hsu

李靜 Chin Lee

藥劑學研究在日本是屬於醫療藥學領域，在歐美國家則屬藥廠研發實務，其精神在於以既定藥物賦予全新設計的處方、添加物或材料，以使藥物本身之藥理活性最大化或使其毒性及副作用最小化，或是延長藥物於體內的留存時間。其意義在於使臨床上的用藥更加安全及有效，進而改善病患之依順性。藥劑學在藥學研究領域內被視為較下游之藥物研發過程，為一門應用科學，本研究室的主要工作便是為藥物設計新的處方內容並探究其改善傳統劑型缺點之程度與能力。

藥物奈米載體之毛囊標靶以治療禿髮

Delivery and targeting of nanoparticles into hair follicles

Nanoparticles can be effective drug delivery systems for penetrating into hair follicles. It has been demonstrated that nanoparticles used for follicular delivery provide some advantages over conventional pathways, including improved skin bioavailability, enhanced penetration depth, prolonged residence duration, fast transport into the skin, and tissue targeting. In recent years the concept of using nanoparticles to treat follicle-related diseases has attracted increasing attention.  Different types of nanosystems may be employed for management of follicular permeation, such as polymeric nanoparticles, metallic nanocrystals, liposomes, and lipid nanoparticles. We investigates the mechanisms of follicles for nanoparticulate penetration, highlighting the therapeutic potential of drug-loaded nanoparticles for treating skin diseases. Special attention is paid to the use of nanoparticles in treating appendage-related disorders, in particular, nanomedical strategies for treating alopecia, acne, and transcutaneous immunization. Issues related to the possible risk of nanoparticulate entry into the skin that may induce a toxicity concern are also discussed. Future progress and the possible advances of follicle-mediated nanoparticle delivery are anticipated.

藥物奈米載體治療急性肺損傷

Injectable nanocarrier delivery to lungs for drug therapy

Different types of injectable nanoparticles, including metallic nanoparticles, polymeric nanocarriers, dendrimers, liposomes, niosomes, and lipid nanoparticles, have been employed to load drugs for lung delivery. Nanoparticles used for lung delivery offer some benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tumor targeting, and minimal side effects. In recent years, the concept of using injectable nanocarriers as vehicles for drug delivery has attracted increasing attention. We systematically investigate the concepts and amelioration mechanisms of the nanomedical techniques for lung-disease therapy. These modalities are useful in the treatment of a wide variety of lung disorders including lung carcinoma, tumor metastasis to the lungs, pulmonary vascular diseases, lung infection, and acute inflammation. Passive targeting by modulating the nanoparticulate structure and the physicochemical properties is an option for efficient drug delivery to the lungs. In addition, active targeting such as antibody or peptide conjugation to nanoparticles is another efficient way to deliver the drugs to the targeted site. We principally focus on the nanomedical application in animal studies.

奈米粒子治療抗藥性病原菌感染

Nanomedical strategies for treating drug-resistant microbiomes

Nanoparticles can be effective drug delivery systems for treating bacterial and fungal infections. It has been demonstrated that nanoparticles used for drug therapy provide some advantages over conventional formulations, including increased solubility, enhanced storage stability, improved permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. In recent years the concept of using nanoparticles to treat drug-resistant microbiome-related diseases has attracted increasing attention. Different types of nanosystems may be employed for antimicrobial management of disease, such as liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric nanoparticles. We systematically study the structures and physicochemical properties of various nanocarriers, highlighting the antibacterial potential of nanoparticles for inhibiting infection. Special attention is paid to the use of nanoparticles in treating skin and appendageal bacteria, in particular, nanomedical strategies for treating cutaneous infection and acne. Issues related to treatment of non-appendageal bacteria and fungi are also investigated.

低能量飛梭雷射促進大分子及基因藥物經皮吸收

Lasers as a strategy for promoting drug delivery via skin

Using lasers can be an effective drug-permeation-enhancement approach for facilitating drug delivery into or across the skin. The controlled disruption and ablation of the stratum corneum (SC), the predominant barrier for drug delivery, is achieved by the use of lasers. The possible mechanisms of laser-assisted drug permeation are the direct ablation of the skin barrier, optical breakdown by a photomechanical wave (PW), and a photothermal effect. It has been demonstrated that ablative approaches for enhancing drug transport provide some advantages, including increased bioavailability, fast treatment time, quick recovery of SC integrity, and the fact that skin surface contact is not needed. In recent years, the concept of using laser techniques to treat the skin has attracted increasing attention. Lasers with different wavelengths and types are employed to increase drug permeation. These include the ruby laser, the erbium:yttrium-gallium-garnet (Er:YAG) laser, the Nd:YAG laser, the CO₂ laser, and the fractional laser. The laser modality is useful to enhance the permeation of a wide variety of permeants, such as small-molecule drugs, macromolecules, and nanoparticles. This potential use of the laser affords a new treatment for topical/transdermal application with significant efficacy. Further studies using a large group for humans or patients are needed to confirm and clarify the findings in animal studies. Although the laser fluence or output energy used for enhancing drug absorption is much lower than for treatment of skin disorders and rejuvenation, the safety of using lasers is still an issue. Caution should be used in optimizing the feasible conditions of the lasers in balancing the effectiveness of permeation enhancement and skin damage.

siRNA 之非侵入性經皮吸收促進策略

Noninvasive approach for enhancing small interfering RNA delivery percutaneously

Topically applied small interfering RNA (siRNA) can be an effective treatment for skin disorders. Using noninvasive strategies can be a safe and effective siRNA-permeation-enhancement approach for facilitating skin delivery. It has been demonstrated that noninvasive approaches for enhancing siRNA transport provide some advantages, including enhanced storage stability, targeted delivery, improved permeability and increased bioavailability. In recent years, the concept of using noninvasive enhancement techniques to promote RNA interference (RNAi) therapy for cutaneous disorders has attracted increasing attention. These techniques include: nanomedicine, penetration enhancers, matrix-based delivery, microneedles, iontophoresis, electroporation and lasers. These modalities are useful for enhancing the permeation of a wide variety of siRNA for treating skin cancers, gene-related diseases, immune-related diseases and cutaneous wounds. The potential use of the noninvasive approaches affords a new treatment for topical siRNA application with significant efficacy. Further studies using a large group for humans or patients are needed to confirm and clarify the findings in animal studies. Although a safe and non-toxic outcome is claimed, the possible adverse effects and irritation elicited by the noninvasive techniques cannot be ignored. Caution should be used in optimizing the feasible conditions of the approaches in balancing the effectiveness of permeation enhancement and skin disruption.

共伴前驅藥改善藥物生體可用率及傳輸能力

The codrug approach for facilitating bioactivity and drug delivery

Codrug or mutual prodrug is a drug design approach to chemically bind two or more drugs to improve therapeutic efficiency or decrease adverse effects. The codrug can be cleaved in the body to generate parent actives. The codrug itself can be inactive, less active, or more active than the parent agents. It has been demonstrated that codrugs possess some benefits over conventional drugs, including enhanced solubility, increased permeation for passing across biomembranes, prolonged half-life for extending the therapeutic period, and reduced toxicity. Codrugs are predominantly used to treat some conditions such as neurodegenerative, cardiovascular, cancerous, infectious, and inflammatory disorders. Many codrugs are developed to increase lipophilicity for better transport into/across biomembranes, especially the skin and cornea. A targeted delivery of codrugs to specific tissues or organs thus can be achieved to promote bioavailability. The chemical and enzymatic hydrolysis, bioactivity, and pharmacokinetics of codrugs are systematically explored in our laboratory. Additional profiles pertaining to clinical trials will support further applicability of codrug therapy.