Investigation of lipid nanocarriers and microspicule gel for dermal delivery of porcine placenta extract

Authors

  • Kritsanaporn Tansathien Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand
  • Koranat Dechsri Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand
  • Praneet Opanasopit Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand
  • Nopparat Nuntharatanapong Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand
  • Monrudee Sukma Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand
  • Worranan Rangsimawong Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand

Keywords:

dermal delivery, liposome, noisome, PEGylation, microspicule, porcine placenta extract, gels

Abstract

The primary active ingredient of porcine placenta extract (PPE) is a total protein that is limited the transportation of its content into the skin. The objective was to investigate the dermal delivery of PPE using lipid nanocarriers and a microspicule (MS) gel. The liposomes (LI), PEGylated liposomes (P-LI), niosomes (NI), and PEGylated niosomes (P-NI) for loading PPE were formulated and characterized the physicochemical properties. PPE-loaded nanocarriers were added to the MS gel. The in vitro skin deposition study and confocal laser scanning microscopy (CLSM) were performed.  For the results, all formulations were nanometers (84 to 172 nm) in size with narrow size distribution and negatively charged (-11 to -31 mV). The percent loading capacity (% LC) of NI (26.43 ± 1.69 %) was higher than that of P-NI (23.97 ± 0.55 %), LI (4.87 ± 0.13 %), and P-LI (4.25 ± 0.05 %), respectively. All nanocarriers were successfully mixed with MS gel. After applying the formulations to the skin for four hours, NI-MS gel showed significantly higher total protein deposited into the skin (345.19 ± 53.65 µg/ml) than that the gel-based formulation did (175.56 ± 67.28 µg/ml) (p<0.05). The CLSM study confirmed that the NI-MS gel could deliver bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as the macromolecular protein marker through the stratum corneum barrier into the deep skin. In conclusion, the NI-MS gel exhibited suitable physicochemical properties, suggesting that this model could play an essential role as a dermal delivery system for PPE and other macromolecules.

References

Abdelkader, H., Alani, A. W. G., & Alany, R. G. (2014). Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug Delivery, 21(2), 87-100. https://doi.org/10.3109/10717544.2013.838077

Alvarez-Román, R., Naik, A., Kalia, Y. N., Fessi, H., & Guy, R. H. (2004). Visualization of skin penetration using confocal laser scanning microscopy. European Journal of Pharmaceutics and Biopharmaceutics, 58(2), 301-316. https://doi.org/10.1016/j.ejpb.2004.03.027

An, Y.-H., Park, M. J., Lee, J., Ko, J., Kim, S.-H., Kang, D. H., & Hwang, N. S. (2020). Recent advances in the transdermal delivery of protein therapeutics with a combinatorial system of chemical adjuvants and physical penetration enhancements. Advanced Therapeutics, 3(2), 1900116. https://doi.org/10.1002/adtp.201900116

Bajracharya, R., Song, J. G., Back, S. Y., & Han, H. K. (2019). Recent advancements in non-invasive formulations for protein drug delivery. Computational and Structural Biotechnology Journal, 17, 1290-1308. https://doi.org/10.1016/j.csbj.2019.09.004

Benson, H. A. E., Grice, J. E., Mohammed, Y., Namjoshi, S., & Roberts, M. S. (2019). Topical and transdermal drug delivery: from simple potions to smart technologies. Current Drug Delivery, 16(5), 444-460. https://doi.org/10.2174/1567201816666190201143457

Chaturvedi, S., & Garg, A. (2021). An insight of techniques for the assessment of permeation flux across the skin for optimization of topical and transdermal drug delivery systems. Journal of Drug Delivery Science and Technology, 62, 102355. https://doi.org/https://doi.org/10.1016/j.jddst.2021.102355

Chaulagain, B., Jain, A., Tiwari, A., Verma, A., & Jain, S. K. (2018). Passive delivery of protein drugs through transdermal route. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup1), 472-487. https://doi.org/10.1080/21691401.2018.1430695

Cristiano, M. C., Cilurzo, F., Carafa, M., & Paolino, D. (2018). Chapter 4 - Innovative vesicles for dermal and transdermal drug delivery. In A. M. Grumezescu (Ed.), Lipid Nanocarriers for Drug Targeting. Newyork, US: William Andrew Publishing. https://doi.org/https://doi.org/10.1016/B978-0-12-813687-4.00004-9

El Maghraby, G. M., Barry, B. W., & Williams, A. (2008). Liposomes and skin: from drug delivery to model membranes. European journal of pharmaceutical sciences, 34(4-5), 203-222. https://doi.org/10.1016/j.ejps.2008.05.002

Ge, X., Wei, M., He, S., & Yuan, W.-E. (2019). Advances of non-ionic surfactant vesicles (niosomes) and their application in drug delivery. Pharmaceutics, 11(2), 55. https://doi.org/10.3390/pharmaceutics11020055

Ghanbarzadeh, S., Khorrami, A., & Arami, S. (2015). Nonionic surfactant-based vesicular system for transdermal drug delivery. Drug Delivery, 22(8), 1071-1077. https://doi.org/10.3109/10717544.2013.873837

Gharbavi, M., Amani, J., Kheiri-Manjili, H., Danafar, H., & Sharafi, A. (2018). Niosome: a promising nanocarrier for natural drug delivery through blood-brain barrier. Advances in Pharmacological Sciences, 2018, 6847971. https://doi.org/10.1155/2018/6847971

Hong, K.-B., Park, Y., Kim, J. H., Kim, J. M., & Suh, H. J. (2015). Effects of porcine placenta extract ingestion on ultraviolet B-induced skin damage in hairless mice. Korean journal for food science of animal resources, 35(3), 413-420. https://doi.org/10.5851/kosfa.2015.35.3.413

Hsiao, C. Y., Yang, S. C., Alalaiwe, A., & Fang, J. Y. (2019). Laser ablation and topical drug delivery: a review of recent advances. Expert Opinion on Drug Delivery, 16(9), 937-952. https://doi.org/10.1080/17425247.2019.1649655.

Huang, Y., Chen, J., Chen, X., Gao, J., & Liang, W. (2008). PEGylated synthetic surfactant vesicles (Niosomes): novel carriers for oligonucleotides. Journal of Materials Science: Materials in Medicine, 19(2), 607-614. https://doi.org/10.1007/s10856-007-3193-4

Kirkby, M., Hutton, A. R. J., & Donnelly, R. F. (2020). Microneedle mediated transdermal delivery of protein, peptide and antibody based therapeutics: current status and future considerations. Pharmaceutical Research, 37(6), 117. https://doi.org/10.1007/s11095-020-02844-6

Liang, X., Zhang, J., Ou, H., Chen, J., Mitragotri, S., & Chen, M. (2020). Skin delivery of siRNA using sponge spicules in combination with cationic flexible liposomes. Mol. Ther. Nucleic Acids, 20, 639-648. https://doi.org/10.1016/j.omtn.2020.04.003

Manconi, M., Sinico, C., Valenti, D., Lai, F., & Fadda, A. M. (2006). Niosomes as carriers for tretinoin: III. A study into the in vitro cutaneous delivery of vesicle-incorporated tretinoin. International journal of pharmaceutics, 311(1-2), 11-19. https://doi.org/10.1016/j.ijpharm.2005.11.045

Massella, D., Leone, F., Peila, R., Barresi, A. A., & Ferri, A. (2018). Functionalization of cotton fabrics with polycaprolactone nanoparticles for transdermal release of melatonin. Journal of Functional Biomaterials, 9(1), 1-15. https://doi.org/10.3390/jfb9010001

Mirtaleb, M. S., Shahraky, M. K., Ekrami, E., & Mirtaleb, A. (2021). Advances in biological nano-phospholipid vesicles for transdermal delivery: A review on applications. Journal of Drug Delivery Science and Technology, 61, 102331. https://doi.org/https://doi.org/10.1016/j.jddst.2021.102331

Münch, S., Wohlrab, J., & Neubert, R. H. H. (2017). Dermal and transdermal delivery of pharmaceutically relevant macromolecules. European Journal of Pharmaceutics and Biopharmaceutics, 119, 235-242. https://doi.org/10.1016/j.ejpb.2017.06.019

Muralidhar, R. V., & Panda, T. (1999). Useful products from human placenta. Bioprocess Engineering, 20(1), 23-25. https://doi.org/10.1007/s004490050554

Nagae, M., Nagata, M., Teramoto, M., Yamakawa, M., Matsuki, T., Ohnuki, K., & Shimizu, K. (2020). Effect of porcine placenta extract supplement on skin condition in healthy adult women: a randomized, double-blind placebo-controlled study. Nutrients, 12(6), 1671. https://doi.org/10.3390/nu12061671

Nigro, F., Cerqueira Pinto, C. D. S., dos Santos, E. P., & Mansur, C. R. E. (2022). Niosome-based hydrogel as a potential drug delivery system for topical and transdermal applications. International Journal of Polymeric Materials and Polymeric Biomaterials, 71(6), 444-461. https://doi.org/10.1080/00914037.2020.1848833

Okore, V. C., Attama, A. A., Ofokansi, K. C., Esimone, C. O., & Onuigbo, E. B. (2011). Formulation and evaluation of niosomes. Indian journal of pharmaceutical sciences, 73(3), 323-328. https://doi.org/10.4103/0250-474X.93515

Pan, S. Y., Chan, M. K. S., Wong, M. B. F., Klokol, D., & Chernykh, V. (2017). Placental therapy: an insight to their biological and therapeutic properties. Journal of Medicine and Therapeutics, 1(3), 1-6. https://doi.org/10.15761/JMT.1000118

Peña-Juárez, M., Guadarrama-Escobar, O. R., & Escobar-Chávez, J. J. (2022). Transdermal delivery systems for biomolecules. Journal of Pharmaceutical Innovation, 17(2), 319-332. https://doi.org/10.1007/s12247-020-09525-2

Pengnam, S., Patrojanasophon, P., Rojanarata, T., Ngawhirunpat, T., Yingyongnarongkul, B. E., Radchatawedchakoon, W., & Opanasopit, P. (2019). A novel plier-like gemini cationic niosome for nucleic acid delivery. Journal of Drug Delivery Science and Technology, 52, 325-333. https://doi.org/10.1016/j.jddst.2019.04.032

Pierre, M. B. R., & dos Santos Miranda Costa, I. (2011). Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Archives of Dermatological Research, 303(9), 607. https://doi.org/10.1007/s00403-011-1166-4

Rabiei, M., Kashanian, S., Samavati, S. S., Jamasb, S., & McInnes, S. J. P. (2020). Nanomaterial and advanced technologies in transdermal drug delivery. Journal of Drug Targeting, 28(4), 356-367. https://doi.org/10.1080/1061186X.2019.1693579

Ramadon, D., McCrudden, M. T., Courtenay, A. J., & Donnelly, R. F. (2022). Enhancement strategies for transdermal drug delivery systems: Current trends and applications. Drug Delivery and Translational Research, 12(4), 758-791. https://doi.org/10.1007/s13346-021-00909-6

Rangsimawong, W., Opanasopit, P., Rojanarata, T., Panomsuk, S. & Ngawhirunpat, T. (2017). Influence of sonophoresis on transdermal drug delivery of hydrophilic compound-loaded lipid nanocarriers. Pharmaceutical Development and Technology, 22(4), 597-605. https://doi.org/10.1080/10837450.2016.1221428

Rangsimawong, W., Opanasopit, P., Rojanarata, T., Duangjit, S., & Ngawhirunpat, T. (2016). Skin transport of hydrophilic compound-loaded PEGylated lipid nanocarriers: comparative study of liposomes, niosomes, and solid lipid nanoparticles. Biological and Pharmaceutical Bulletin, 39(8), 1254-1262. https://doi.org/10.1248/bpb.b15-00981

Tansathien, K., Chareanputtakhun, P., Ngawhirunpat, T., Opanasopit, P., & Rangsimawong, W. (2021). Hair growth promoting effect of bioactive extract from deer antler velvet-loaded niosomes and microspicules serum. International Journal of Pharmaceutics, 597, 120352. https://doi.org/10.1016/j.ijpharm.2021.120352

Tansathien, K., Suriyaaumporn, P., Charoenputtakhun, P., Ngawhirunpat, T., Opanasopit, P., & Rangsimawong, W. (2019). Development of sponge microspicule cream as a transdermal delivery system for protein and growth factors from deer antler velvet extract. Biological and Pharmaceutical Bulletin, 42(7), 1207-1215. https://doi.org/10.1248/bpb.b19-00158

van Hoogevest, P., & Fahr, A. (2019). Phospholipids in cosmetic carriers. In J. Cornier, C. M. Keck, & M. Van de Voorde (Eds.), Nanocosmetics: From Ideas to Products. New York, US: Springer International Publishing. https://doi.org/10.1007/978-3-030-16573-4_6

Walters, K. A. (2002). The structure and Function of Skin. Dermatological and Transdermal Formulation. (Walters KA, Robert MS eds.) Florida, US: CRC Press.

Wang, J., Wei, Y., Fei, Y. R., Fang, L., Zheng, H. S., Mu, C. F., ... & Zhang, Y. S. (2017). Preparation of mixed monoterpenes edge activated PEGylated transfersomes to improve the in vivo transdermal delivery efficiency of sinomenine hydrochloride. International Journal of Pharmaceutics, 533(1), 266-274. https://doi.org/https://doi.org/10.1016/j.ijpharm.2017.09.059

Yang, K., Bai, S., & Sun, Y. (2008). Protein adsorption dynamics in cation-exchange chromatography quantitatively studied by confocal laser scanning microscopy. Chemical Engineering Science, 63(16), 4045-4054. https://doi.org/https://doi.org/10.1016/j.ces.2008.05.013

Yu, Y. Q., Yang, X., Wu, X. F., & Fan, Y. B. (2021). Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: novel strategies for effective transdermal applications. Frontiers in Bioengineering and Biotechnology, 9, 646554. https://doi.org/10.3389/fbioe.2021.646554

Zhai, H., Zhang, C., Ou, H., & Chen, M. (2021). Transdermal delivery of heparin using low-frequency sonophoresis in combination with sponge spicules for venous thrombosis treatment. Biomaterials Science, 9(16), 5612-5625. https://doi.org/10.1039/D1BM00703C

Zhang, C., Zhang, K., Zhang, J., Ou, H., Duan, J., Zhang, S., ... & Chen, M. (2019). Skin delivery of hyaluronic acid by the combined use of sponge spicules and flexible liposomes. Biomater. Sci., 7(4), 1299-1310. https://doi.org/10.1039/C8BM01555D

Zheng, H., Xu, C., Fei, Y., Wang, J., Yang, M., Fang, L., ... & Tao, C. (2020). Monoterpenes-containing PEGylated transfersomes for enhancing joint cavity drug delivery evidenced by CLSM and double-sited microdialysis. Materials Science and Engineering: C, 113, 110929. https://doi.org/https://doi.org/10.1016/j.msec.2020.110929

Downloads

Published

2022-12-26

How to Cite

Kritsanaporn Tansathien, Koranat Dechsri, Praneet Opanasopit, Nopparat Nuntharatanapong, Monrudee Sukma, & Worranan Rangsimawong. (2022). Investigation of lipid nanocarriers and microspicule gel for dermal delivery of porcine placenta extract. Journal of Current Science and Technology, 12(3), 505–516. Retrieved from https://ph04.tci-thaijo.org/index.php/JCST/article/view/288

Issue

Section

Research Article