Impact of Anti-PEG IgM Induced via the Topical Application of a Cosmetic Product Containing PEG Derivatives on the Antitumor Effects of PEGylated Liposomal Antitumor Drug Formulations in Mice
Poly(ethylene glycol) (PEG) is used in many common products, such as cosmetics. PEG, however, is also used to covalently conjugate drug molecules, proteins, or nanocarriers, which is termed PEGylation, to serve as a shield against the natural immune system of the human body. Repeated administration of some PEGylated products, however, is known to induce anti-PEG antibodies. In addition, preexisting anti-PEG antibodies are now being detected in healthy individuals who have never received PEGylated therapeutics. Both treatment-induced and preexisting anti-PEG antibodies alter the pharmacokinetic properties, which can result in a subsequent reduction in the therapeutic efficacy of administered PEGylated therapeutics through the so-called accelerated blood clearance (ABC) phenomenon. Moreover, these anti-PEG antibodies are widely reported to be related to severe hypersensitivity reactions following the administration of PEGylated therapeutics, including COVID-19 vaccines. We recently reported that the topical application of a cosmetic product containing PEG derivatives induced anti-PEG immunoglobulin M (IgM) in a mouse model. Our finding indicates that the PEG derivatives in cosmetic products could be a major cause of the preexistence of anti-PEG antibodies in healthy individuals. In this study, therefore, the pharmacokinetics and therapeutic effects of Doxil (doxorubicin hydrochloride-loaded PEGylated liposomes) and oxaliplatin-loaded PEGylated liposomes (Liposomal l-OHP) were studied in mice. The anti-PEG IgM antibodies induced by the topical application of cosmetic products obviously accelerated the blood clearance of both PEGylated liposomal formulations. Moreover, in C26 tumor-bearing mice, the tumor growth suppressive effects of both Doxil and Liposomal l-OHP were significantly attenuated in the presence of anti-PEG IgM antibodies induced by the topical application of cosmetic products. These results confirm that the topical application of a cosmetic product containing PEG derivatives could produce preexisting anti-PEG antibodies that then affect the therapeutic efficacy of subsequent doses of PEGylated therapeutics.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Molecular pharmaceutics - 21(2024), 2 vom: 05. Feb., Seite 622-632 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gaballa, Sherif A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 06.02.2024 Date Revised 06.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1021/acs.molpharmaceut.3c00774 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367638584 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367638584 | ||
| 003 | DE-627 | ||
| 005 | 20240206232135.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240126s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acs.molpharmaceut.3c00774 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1282.xml |
| 035 | |a (DE-627)NLM367638584 | ||
| 035 | |a (NLM)38273445 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gaballa, Sherif A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of Anti-PEG IgM Induced via the Topical Application of a Cosmetic Product Containing PEG Derivatives on the Antitumor Effects of PEGylated Liposomal Antitumor Drug Formulations in Mice |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.02.2024 | ||
| 500 | |a Date Revised 06.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Poly(ethylene glycol) (PEG) is used in many common products, such as cosmetics. PEG, however, is also used to covalently conjugate drug molecules, proteins, or nanocarriers, which is termed PEGylation, to serve as a shield against the natural immune system of the human body. Repeated administration of some PEGylated products, however, is known to induce anti-PEG antibodies. In addition, preexisting anti-PEG antibodies are now being detected in healthy individuals who have never received PEGylated therapeutics. Both treatment-induced and preexisting anti-PEG antibodies alter the pharmacokinetic properties, which can result in a subsequent reduction in the therapeutic efficacy of administered PEGylated therapeutics through the so-called accelerated blood clearance (ABC) phenomenon. Moreover, these anti-PEG antibodies are widely reported to be related to severe hypersensitivity reactions following the administration of PEGylated therapeutics, including COVID-19 vaccines. We recently reported that the topical application of a cosmetic product containing PEG derivatives induced anti-PEG immunoglobulin M (IgM) in a mouse model. Our finding indicates that the PEG derivatives in cosmetic products could be a major cause of the preexistence of anti-PEG antibodies in healthy individuals. In this study, therefore, the pharmacokinetics and therapeutic effects of Doxil (doxorubicin hydrochloride-loaded PEGylated liposomes) and oxaliplatin-loaded PEGylated liposomes (Liposomal l-OHP) were studied in mice. The anti-PEG IgM antibodies induced by the topical application of cosmetic products obviously accelerated the blood clearance of both PEGylated liposomal formulations. Moreover, in C26 tumor-bearing mice, the tumor growth suppressive effects of both Doxil and Liposomal l-OHP were significantly attenuated in the presence of anti-PEG IgM antibodies induced by the topical application of cosmetic products. These results confirm that the topical application of a cosmetic product containing PEG derivatives could produce preexisting anti-PEG antibodies that then affect the therapeutic efficacy of subsequent doses of PEGylated therapeutics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a accelerated blood clearance (ABC) phenomenon | |
| 650 | 4 | |a anti-PEG IgM antibodies | |
| 650 | 4 | |a cosmetics | |
| 650 | 4 | |a poly(ethylene glycol) (PEG) | |
| 650 | 4 | |a preexisting antibodies | |
| 650 | 7 | |a liposomal doxorubicin |2 NLM | |
| 650 | 7 | |a Liposomes |2 NLM | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Immunoglobulin M |2 NLM | |
| 650 | 7 | |a Polyethylene Glycols |2 NLM | |
| 650 | 7 | |a 3WJQ0SDW1A |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 700 | 1 | |a Shimizu, Taro |e verfasserin |4 aut | |
| 700 | 1 | |a Takata, Haruka |e verfasserin |4 aut | |
| 700 | 1 | |a Ando, Hidenori |e verfasserin |4 aut | |
| 700 | 1 | |a Ibrahim, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Emam, Sherif E |e verfasserin |4 aut | |
| 700 | 1 | |a Amorim Matsuo, Nana Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yuri |e verfasserin |4 aut | |
| 700 | 1 | |a Naguib, Youssef W |e verfasserin |4 aut | |
| 700 | 1 | |a Mady, Fatma M |e verfasserin |4 aut | |
| 700 | 1 | |a Khaled, Khaled A |e verfasserin |4 aut | |
| 700 | 1 | |a Ishida, Tatsuhiro |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular pharmaceutics |d 2004 |g 21(2024), 2 vom: 05. Feb., Seite 622-632 |w (DE-627)NLM154556807 |x 1543-8392 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2024 |g number:2 |g day:05 |g month:02 |g pages:622-632 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.molpharmaceut.3c00774 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2024 |e 2 |b 05 |c 02 |h 622-632 | ||