Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach
Breast cancer is the most common invasive cancer in women worldwide, having a significant impact on women's well-being. Early diagnosis of breast cancer followed by appropriate treatment is considered the best survival factor. Microneedles (MN) have been utilized for non-invasive localized brea...
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| Veröffentlicht in: | Journal of controlled release 2024-12, Vol.376, p.354-368 |
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| creator | Heikal, Lamia A. Ashour, Asmaa A. Aboushanab, Alaa R. El-Kamel, Amal H. Zaki, Inass I. El-Moslemany, Riham M. |
| description | Breast cancer is the most common invasive cancer in women worldwide, having a significant impact on women's well-being. Early diagnosis of breast cancer followed by appropriate treatment is considered the best survival factor. Microneedles (MN) have been utilized for non-invasive localized breast cancer treatment. The combination of nano-carriers with MN technology represents an appealing strategy for improving drug delivery efficacy. It is worth noting that atorvastatin (ATV) has received substantial interest as a drug with potential anticancer activity. Our study aimed to formulate an ATV-loaded bioactive pumpkin seed oil vesicular nanocarrier; pumpkisomes (PUMP) for enhanced localized delivery to breast cancer using MN. The selected PUMP formulation had a particle size of 151.8 ± 2.7 nm, zeta potential of −54.1 mV, and % entrapment efficiency of 73 %. PUMP showed a sustained ATV release, potent selective cytotoxic effect (IC50 of 2.82 ± 0.02 μg/mL), enhanced internalization (2.8-fold increase compared to the free drug), and potent anti-migratory effect on MDA-MB-231 cells (21.15 ± 3.6 % wound closure compared to 80.81 ± 4.1 % for free drug). Moreover, integrating ATV-PUMP in dissolving microneedles (ATV-PUMP@dMN) showed a quick dissolution rate and appropriate mechanical strength with high piercing efficiency. ATV permeation across the skin from ATV-PUMP@dMN was also improved (1.8-fold increase compared to ATV-PUMP@gel). ATV-PUMP@dMN demonstrated an efficient anticancer effect when applied in an Ehrlich ascites mammary tumor model attaining significant improvement in ATV antiproliferative (PTEN and Ki-67), antiangiogenic (VEGF) and apoptotic (Bcl2, Bax and caspase3) effects restoring tumor biomarkers to levels comparable to the negative control group. Thus, our study presents PUMP as a novel and promising bioactive vesicular nanosystem with potential synergistic effect with ATV or other antitumor drugs. PUMP-integrated MN could be considered a promising platform for future applications in localized breast cancer therapy.
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| doi_str_mv | 10.1016/j.jconrel.2024.10.013 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>ISSN: 1873-4995</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2024.10.013</identifier><identifier>PMID: 39413849</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; antineoplastic activity ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacokinetics ; Apoptosis ; ascites ; atorvastatin ; Atorvastatin - administration & dosage ; Bioactive nanovesicles ; biomarkers ; breast neoplasms ; Breast Neoplasms - drug therapy ; cancer therapy ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Survival - drug effects ; cytotoxicity ; Drug Delivery Systems ; Drug Liberation ; drugs ; early diagnosis ; Female ; Humans ; mammary neoplasms (animal) ; Mice ; Microneedles ; nanocarriers ; Needles ; particle size ; permeability ; PTEN ; pumpkin oil ; Pumpkin seed oil ; Repurposed drug ; strength (mechanics) ; synergism ; zeta potential</subject><ispartof>Journal of controlled release, 2024-12, Vol.376, p.354-368</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c276t-6ad87b0622aef12bf8498c0438ddffe6d65d6e0545ed7d51f1f98eab891154953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S016836592400676X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39413849$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heikal, Lamia A.</creatorcontrib><creatorcontrib>Ashour, Asmaa A.</creatorcontrib><creatorcontrib>Aboushanab, Alaa R.</creatorcontrib><creatorcontrib>El-Kamel, Amal H.</creatorcontrib><creatorcontrib>Zaki, Inass I.</creatorcontrib><creatorcontrib>El-Moslemany, Riham M.</creatorcontrib><title>Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Breast cancer is the most common invasive cancer in women worldwide, having a significant impact on women's well-being. Early diagnosis of breast cancer followed by appropriate treatment is considered the best survival factor. Microneedles (MN) have been utilized for non-invasive localized breast cancer treatment. The combination of nano-carriers with MN technology represents an appealing strategy for improving drug delivery efficacy. It is worth noting that atorvastatin (ATV) has received substantial interest as a drug with potential anticancer activity. Our study aimed to formulate an ATV-loaded bioactive pumpkin seed oil vesicular nanocarrier; pumpkisomes (PUMP) for enhanced localized delivery to breast cancer using MN. The selected PUMP formulation had a particle size of 151.8 ± 2.7 nm, zeta potential of −54.1 mV, and % entrapment efficiency of 73 %. PUMP showed a sustained ATV release, potent selective cytotoxic effect (IC50 of 2.82 ± 0.02 μg/mL), enhanced internalization (2.8-fold increase compared to the free drug), and potent anti-migratory effect on MDA-MB-231 cells (21.15 ± 3.6 % wound closure compared to 80.81 ± 4.1 % for free drug). Moreover, integrating ATV-PUMP in dissolving microneedles (ATV-PUMP@dMN) showed a quick dissolution rate and appropriate mechanical strength with high piercing efficiency. ATV permeation across the skin from ATV-PUMP@dMN was also improved (1.8-fold increase compared to ATV-PUMP@gel). ATV-PUMP@dMN demonstrated an efficient anticancer effect when applied in an Ehrlich ascites mammary tumor model attaining significant improvement in ATV antiproliferative (PTEN and Ki-67), antiangiogenic (VEGF) and apoptotic (Bcl2, Bax and caspase3) effects restoring tumor biomarkers to levels comparable to the negative control group. Thus, our study presents PUMP as a novel and promising bioactive vesicular nanosystem with potential synergistic effect with ATV or other antitumor drugs. PUMP-integrated MN could be considered a promising platform for future applications in localized breast cancer therapy.
[Display omitted]</description><subject>Animals</subject><subject>antineoplastic activity</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Apoptosis</subject><subject>ascites</subject><subject>atorvastatin</subject><subject>Atorvastatin - administration & dosage</subject><subject>Bioactive nanovesicles</subject><subject>biomarkers</subject><subject>breast neoplasms</subject><subject>Breast Neoplasms - drug therapy</subject><subject>cancer therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>cytotoxicity</subject><subject>Drug Delivery Systems</subject><subject>Drug Liberation</subject><subject>drugs</subject><subject>early diagnosis</subject><subject>Female</subject><subject>Humans</subject><subject>mammary neoplasms (animal)</subject><subject>Mice</subject><subject>Microneedles</subject><subject>nanocarriers</subject><subject>Needles</subject><subject>particle size</subject><subject>permeability</subject><subject>PTEN</subject><subject>pumpkin oil</subject><subject>Pumpkin seed oil</subject><subject>Repurposed drug</subject><subject>strength (mechanics)</subject><subject>synergism</subject><subject>zeta potential</subject><issn>0168-3659</issn><issn>1873-4995</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2O0zAUhS0EYjoDjwDKkk2KHf8kZoNGI2CQBrGBteXY19TFiYPtFJWnx1ULW1hZuv7OPVfnIPSC4C3BRLzeb_cmzgnCtsMdq7MtJvQR2pChpy2Tkj9Gm8oNLRVcXqHrnPcYY05Z_xRdUckIHZjcoPWTNynOADZAbvxc4FvSBWzz05ddo0tMB52LLn5uQ9S2fizrtHz3OU6VdzE1Y4JKNEbPBlJTdpD0cnzT3DYhGh38ryqxEPwB0rHRy5KiNrtn6InTIcPzy3uDvr5_9-Xuvn34_OHj3e1Da7pelFZoO_QjFl2nwZFudPXkwWBGB2udA2EFtwIwZxxsbzlxxMkB9DhIQjiTnN6gV-e91fbHCrmoyWcDIegZ4poVrVhXg6DyP1DSC9IPTFSUn9GaXM4JnFqSn3Q6KoLVqRy1V5dy1Kmc07iWU3UvLxbrOIH9q_rTRgXengGomRw8JJWNh5qr9QlMUTb6f1j8BgawpYw</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Heikal, Lamia A.</creator><creator>Ashour, Asmaa A.</creator><creator>Aboushanab, Alaa R.</creator><creator>El-Kamel, Amal H.</creator><creator>Zaki, Inass I.</creator><creator>El-Moslemany, Riham M.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>202412</creationdate><title>Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach</title><author>Heikal, Lamia A. ; Ashour, Asmaa A. ; Aboushanab, Alaa R. ; El-Kamel, Amal H. ; Zaki, Inass I. ; El-Moslemany, Riham M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c276t-6ad87b0622aef12bf8498c0438ddffe6d65d6e0545ed7d51f1f98eab891154953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>antineoplastic activity</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Apoptosis</topic><topic>ascites</topic><topic>atorvastatin</topic><topic>Atorvastatin - administration & dosage</topic><topic>Bioactive nanovesicles</topic><topic>biomarkers</topic><topic>breast neoplasms</topic><topic>Breast Neoplasms - drug therapy</topic><topic>cancer therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>cytotoxicity</topic><topic>Drug Delivery Systems</topic><topic>Drug Liberation</topic><topic>drugs</topic><topic>early diagnosis</topic><topic>Female</topic><topic>Humans</topic><topic>mammary neoplasms (animal)</topic><topic>Mice</topic><topic>Microneedles</topic><topic>nanocarriers</topic><topic>Needles</topic><topic>particle size</topic><topic>permeability</topic><topic>PTEN</topic><topic>pumpkin oil</topic><topic>Pumpkin seed oil</topic><topic>Repurposed drug</topic><topic>strength (mechanics)</topic><topic>synergism</topic><topic>zeta potential</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heikal, Lamia A.</creatorcontrib><creatorcontrib>Ashour, Asmaa A.</creatorcontrib><creatorcontrib>Aboushanab, Alaa R.</creatorcontrib><creatorcontrib>El-Kamel, Amal H.</creatorcontrib><creatorcontrib>Zaki, Inass I.</creatorcontrib><creatorcontrib>El-Moslemany, Riham M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heikal, Lamia A.</au><au>Ashour, Asmaa A.</au><au>Aboushanab, Alaa R.</au><au>El-Kamel, Amal H.</au><au>Zaki, Inass I.</au><au>El-Moslemany, Riham M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2024-12</date><risdate>2024</risdate><volume>376</volume><spage>354</spage><epage>368</epage><pages>354-368</pages><issn>0168-3659</issn><issn>1873-4995</issn><eissn>1873-4995</eissn><abstract>Breast cancer is the most common invasive cancer in women worldwide, having a significant impact on women's well-being. Early diagnosis of breast cancer followed by appropriate treatment is considered the best survival factor. Microneedles (MN) have been utilized for non-invasive localized breast cancer treatment. The combination of nano-carriers with MN technology represents an appealing strategy for improving drug delivery efficacy. It is worth noting that atorvastatin (ATV) has received substantial interest as a drug with potential anticancer activity. Our study aimed to formulate an ATV-loaded bioactive pumpkin seed oil vesicular nanocarrier; pumpkisomes (PUMP) for enhanced localized delivery to breast cancer using MN. The selected PUMP formulation had a particle size of 151.8 ± 2.7 nm, zeta potential of −54.1 mV, and % entrapment efficiency of 73 %. PUMP showed a sustained ATV release, potent selective cytotoxic effect (IC50 of 2.82 ± 0.02 μg/mL), enhanced internalization (2.8-fold increase compared to the free drug), and potent anti-migratory effect on MDA-MB-231 cells (21.15 ± 3.6 % wound closure compared to 80.81 ± 4.1 % for free drug). Moreover, integrating ATV-PUMP in dissolving microneedles (ATV-PUMP@dMN) showed a quick dissolution rate and appropriate mechanical strength with high piercing efficiency. ATV permeation across the skin from ATV-PUMP@dMN was also improved (1.8-fold increase compared to ATV-PUMP@gel). ATV-PUMP@dMN demonstrated an efficient anticancer effect when applied in an Ehrlich ascites mammary tumor model attaining significant improvement in ATV antiproliferative (PTEN and Ki-67), antiangiogenic (VEGF) and apoptotic (Bcl2, Bax and caspase3) effects restoring tumor biomarkers to levels comparable to the negative control group. Thus, our study presents PUMP as a novel and promising bioactive vesicular nanosystem with potential synergistic effect with ATV or other antitumor drugs. PUMP-integrated MN could be considered a promising platform for future applications in localized breast cancer therapy.
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| subjects | Animals antineoplastic activity Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacokinetics Apoptosis ascites atorvastatin Atorvastatin - administration & dosage Bioactive nanovesicles biomarkers breast neoplasms Breast Neoplasms - drug therapy cancer therapy Cell Line, Tumor Cell Movement - drug effects Cell Survival - drug effects cytotoxicity Drug Delivery Systems Drug Liberation drugs early diagnosis Female Humans mammary neoplasms (animal) Mice Microneedles nanocarriers Needles particle size permeability PTEN pumpkin oil Pumpkin seed oil Repurposed drug strength (mechanics) synergism zeta potential |
| title | Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach |
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