PLGA-based microparticles loaded with bacterial-synthesized prodigiosin for anticancer drug release: Effects of particle size on drug release kinetics and cell viability

Obayemi, John D.; Danyuo, Y.; Dozie-Nwachukwu, S.; Odusanya, Olushola S.; Anuku, N.; Malatesta, Karen; Yu, Wu; Uhrich, Kathryn E.; Soboyejo, W.O.

doi:10.1016/j.msec.2016.04.071

Cited by 71 publications

(41 citation statements)

References 54 publications

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“…Prodigiosin (PGS) which is also known as 4-methoxy-5-[(Z)-(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl]-1H,1′H-2,2′-bipyrrole contains a C-6 methoxy substituent in the 4-methoxy-2,20-bipyrrolyl ring. The purity of the prodigiosin that was synthesized for conjugation to LHRH was characterized to be 92.5% 35,36 . The presence of the hydrophilic linker (NHS) creates sites for reactions with the methoxy group that is present in the prodigiosin molecule 37 .…”

Section: Resultsmentioning

confidence: 99%

LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer

Obayemi

Salifu

Eluu

et al. 2020

Sci Rep

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Bulk chemotherapy and drug release strategies for cancer treatment have been associated with lack of specificity and high drug concentrations that often result in toxic side effects. This work presents the results of an experimental study of cancer drugs (prodigiosin or paclitaxel) conjugated to Luteinizing Hormone-Releasing Hormone (LHRH) for the specific targeting and treatment of triple negative breast cancer (TNBC). Injections of LHRH-conjugated drugs (LHRH-prodigiosin or LHRH-paclitaxel) into groups of 4-week-old athymic female nude mice (induced with subcutaneous triple negative xenograft breast tumors) were found to specifically target, eliminate or shrink tumors at early, mid and late stages without any apparent cytotoxicity, as revealed by in vivo toxicity and ex vivo histopathological tests. Our results show that overexpressed LHRH receptors serve as binding sites on the breast cancer cells/ tumor and the LHRH-conjugated drugs inhibited the growth of breast cells/tumor in in vitro and in vivo experiments. The inhibitions are attributed to the respective adhesive interactions between LHRH molecular recognition units on the prodigiosin (PGS) and paclitaxel (PTX) drugs and overexpressed LHRH receptors on the breast cancer cells and tumors. The implications of the results are discussed for the development of ligand-conjugated drugs for the specific targeting and treatment of TNBC. Breast cancer is the most commonly diagnosed cancer and the second most frequent cause of death in women 1. In general, breast tumors are intrinsically heterogeneous in nature, making them difficult to detect and treat 2. Approximately, 75-80% of breast cancers are hormone receptor-positive 2,3. Also, these overexpressed receptors are usually estrogen and/or progesterone receptors 2,3. However, Triple Negative Breast Cancer (TNBC) (which represents approximately 10-17% of all breast cancers) does not express estrogen receptors (ER), or progesterone receptors (PR), or the human epidermal growth factor receptor 2 gene (HER2) 4-8. In addition, TNBCs also exhibit distinctive clinical features 7,8 and are more common in younger patients 6 and African American/African women 9. TNBC is an aggressive and immunopathology subtype of breast cancer that usually does not respond to drugs that target ER, PR and HER2 6. Furthermore, since the most common and conventional breast cancer diagnosis and treatment techniques tend to focus and target ER, PR and HER2, it is often difficult to detect 10 and treat 11 TNBCs with conventional targeted hormonal therapy and chemotherapy. The challenges associated with TNBCs

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Section: Resultsmentioning

confidence: 99%

LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer

Obayemi

Salifu

Eluu

et al. 2020

Sci Rep

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“…A recent report indicated that the particle size of the drug-loaded nanoparticles was more conducive to transmission in the human body when it was below 100 nm, which not only improved drug-loading, but also increased the specic surface area for drug delivery. 35 It was reported that drug delivery systems with a particle size between 30 and 200 nm would be suitable for intravenous drug delivery, and lead to preferred accumulation of the drug delivery systems at the tumor site by enhanced permeability and retention (EPR). 31,36 Although many studies have reported that the cellulose nanoparticles delivery system could be accumulated at the solid tumor site in a passive targeting manner by an EPR effect, [37][38][39][40] particles of 20-60 nm have not previously been reported.…”

Section: Preparation Of Cmc-ua and Drug Loadingmentioning

confidence: 99%

Self-assembled nanoparticles based on a carboxymethylcellulose–ursolic acid conjugate for anticancer combination therapy

Liu

et al. 2017

RSC Adv.

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“…Nowadays, most publications focus on the drug-loading capacity and release behaviors of drug-loaded microspheres (MS) better than their morphology which is strongly correlated to drug entrapment and release behaviors (Bile et al., 2015 ; Obayemi et al., 2016 ). To research how the MS morphology exerts effects, researchers have prepared porous drug-loaded MS with hollow core-shell structure and smooth MS with denser matrix structure (Bae et al., 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: in vitro and in vivo evaluations

Zhang

Wang

et al. 2018

Drug Delivery

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Sustained release of therapeutic agents into tumor cells is a potential approach to improve therapeutic efficacy, decrease side effects, and the drug administration frequency. Herein, we used the modified double-emulsion solvent evaporation (DSE) method to prepare a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS). The prepared rough PTX-PLGA-MS possessed microporous surface and highly porous internal structures, which significantly influenced the drug entrapment and release behaviors. The rough MS with an average particle size of 53.47 ± 2.87 μm achieved high drug loading (15.63%) and encapsulation efficiency (92.82%), and provided a favorable sustained drug release. The in vitro antitumor tests of flow cytometry and fluoroimmunoassay revealed that the rough PTX-PLGA-MS displayed effective anti-gliomas activity and enhanced the cellular PTX uptake through adsorptive endocytosis. Both in vitro and in vivo antitumor results demonstrated that the sustained-release PTX could induce the microtubules assembly and the over-expression of Bax and Cyclin B1 proteins, resulting in the microtubule dynamics disruption, G2/M phase arrest, and cell apoptosis accordingly. Furthermore, as the rough PTX-PLGA-MS could disperse and adhere throughout the tumor sites and cause extensive tumor cell apoptosis with one therapeutic course (12 days), they could reduce the system toxicity and drug administration frequency, thus achieving significant tumor inhibitory effects with rapid sustained drug release. In conclusion, our results verified that the rough PTX-PLGA-MS drug release system could serve as a promising treatment to malignant glioma.

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PLGA-based microparticles loaded with bacterial-synthesized prodigiosin for anticancer drug release: Effects of particle size on drug release kinetics and cell viability

Cited by 71 publications

References 54 publications

LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer

LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer

Self-assembled nanoparticles based on a carboxymethylcellulose–ursolic acid conjugate for anticancer combination therapy

Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: in vitro and in vivo evaluations

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