{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T21:35:55Z","timestamp":1787952955759,"version":"build-2784847793"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box\u2013Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 \u00b1 6.2 nm, and 170 \u00b1 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 \u00b1 0.14, 4.5 \u00b1 0.09, and 18.06 \u00b1 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to \u201cwrap\u201d them will be minimized.<\/jats:p>","DOI":"10.3390\/pharmaceutics11110558","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Modified Spraying Technique and Response Surface Methodology for the Preparation and Optimization of Propolis Liposomes of Enhanced Anti-Proliferative Activity against Human Melanoma Cell Line A375"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1477-837X","authenticated-orcid":false,"given":"Hesham","family":"Refaat","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, faculty of Pharmacy, Minia University, Minia 61519, Egypt"},{"name":"Department of Pharmaceutics, faculty of Pharmacy, Deraya University, Minia 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef W.","family":"Naguib","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, faculty of Pharmacy, Minia University, Minia 61519, Egypt"},{"name":"Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9547-2243","authenticated-orcid":false,"given":"Mahmoud M. A.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag 22161, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem A. A.","family":"Sarhan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Alaaeldin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, faculty of Pharmacy, Minia University, Minia 61519, Egypt"},{"name":"Department of clinical Pharmacy, faculty of Pharmacy, Deraya University, Minia 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jep.2007.06.005","article-title":"Chemical composition and biological activity of a new type of Brazilian propolis: Red propolis","volume":"113","author":"Alencar","year":"2007","journal-title":"J. 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