Nanoparticles For Breast Cancer Treatment Research Articles

Mitoxantrone-Derivative Drug Structure-Directing Agent for the Synthesis of Magnetic Mesoporous Silica Nanoparticles for Breast Cancer Treatment

Mitoxantrone-Derivative Drug Structure-Directing Agent for the Synthesis of Magnetic Mesoporous Silica Nanoparticles for Breast Cancer Treatment

Innovative transdermal doxorubicin patches prepared using greenly synthesized iron oxide nanoparticles for breast cancer treatment

ABSTRACT An innovative strategy was formulated to overcome the challenges in delivering doxorubicin (DOX) for breast cancer treatment. Transdermal patches were prepared using carbopol 971 (CP) and polyvinyl alcohol (PVA) loaded with starch-coated iron oxide nanoparticles conjugated to DOX (DOX@St-IONPs). The patches’ physicochemical properties, in vitro drug diffusion, alongside the physical properties of DOX@St-IONPs, and their impact on breast cancer cell lines’ viability were examined. The M1 patch, with a 1:1 CP:PVA ratio and DOX@St-IONPs, showed unique properties, indicating effective delivery. It maintained consistent thickness, weight, and 97% DOX loading. Demonstrated flexibility and acceptable surface pH. M1 displayed fivefold increased drug penetration compared to free DOX patches (flux of 14.85 µg/cm2/h and permeability of 0.95 cm/h), with higher cytotoxicity against triple-negative breast cancer. These results propose promising non-invasive DOX delivery through the developed patches.

Advancements in the Utilization of Metal Nanoparticles for Breast Cancer Treatment: An In Vivo Studies Update

Breast cancer continues to pose a significant threat to women’s health around the globe, requiring continuous research and innovation in treatment. In recent years, metal nanoparticles have emerged as a promising means of treating breast cancer with greater precision and efficiency. The in vivo studies have indicated that metal nanoparticles, such as gold, silver, and platinum, have demonstrated a remarkable ability to selectively target breast cancer cells while sparing healthy tissue. These nanoparticles’ size, shape, and surface chemistry can be altered to enhance their biocompatibility, stability, and drug-loading capacity. They are also highly versatile for therapeutic applications due to their unique physicochemical properties, such as drug delivery, photothermal therapy, and imaging. This review focuses on recent in vivo studies evaluating metal nanoparticles’ safety and efficacy in treating breast cancer. Several studies have demonstrated that metal nanoparticles can trigger apoptosis, inhibit tumor growth, and reduce metastasis in cancer cells. Furthermore, using these nanoparticles with traditional chemotherapy and radiotherapy has demonstrated a synergistic effect, enhancing treatment efficacy. This review also examines the challenges and concerns associated with the clinical translation of metal nanoparticles. Factors like biocompatibility, pharmacokinetics, and long-term safety profiles are discussed in the context of regulatory approval and patient-specific considerations. In conclusion, this review highlights the evolving landscape of breast cancer treatment with the development of metal nanoparticles, as evidenced by recent in vivo studies. In addition to their therapeutic versatility, these nanoparticles can potentially improve patient outcomes and decrease the burden of breast cancer on society.

Efficient synergistic combination effect of curcumin with piperine by polymeric magnetic nanoparticles for breast cancer treatment

Although it has been reported that the co-delivery of drugs can be beneficial to patients to kill breast cancer cells, the delivery methods could only be employed to effectively encapsulate individual curcumin (CUR) or piperine (PIP) molecules due to their different molecular polarities. Therefore, in the current research, an attempt was made to overcome the limitation of the co-delivery of CUR and PIP nanoparticles for breast cancer therapy. To manage locoregional breast cancer recurrence, a magnetic co-delivery system of CUR and PIP against MCF-7 breast cancer cells was examined. CUR and PIP demonstrated synergistic effects for breast cancer therapy when utilized together. However, due to the different polarities of CUR and PIP, it was difficult to co-encapsulate them in conventional delivery systems. Moreover, their low bioavailability, hydrophobic nature, and low cellular uptake limit its usage for cancer therapy. In the current study, to overcome the issues and improves its therapeutic efficacy, CUR and PIP-loaded zein/chitosan-coated iron oxide (Chit-PIP/[email protected]3O4) were prepared via a combination of anti-solvent precipitation and layer-by-layer deposition. X-ray diffraction (XRD) analysis revealed magnetite cores and also showed that the binding process did not change the Fe3O4 phase. A vibrational sample magnetometer confirmed that the saturation of sample magnetization was 60 and 40 emu/g for pure Fe3O4 and nanocomposite, respectively. Nanoparticles with an average size of 20 nm were prepared. The drug-loading content of CUR and PIP was approximately 18% and 16%, respectively. CUR and PIP release from Chit-PIP/[email protected]3O4 was faster at the extracellular pH of around tumors (6.5) than in normal tissues (7.4), an interesting degree of pH sensitivity. The MTT assay exhibited that PIP/CUR-loaded polymeric magnetic nanoparticles had significant synergistic cytotoxicity against MCF-7 cells compared with other groups. These results demonstrate that the combination of dual-drug loaded polymeric magnetic nanoparticles holds promise for the targeted treatment of cancer cells.

Macrophage Cell Membrane Coating on Piperine-Loaded MIL-100(Fe) Nanoparticles for Breast Cancer Treatment

Piperine (PIP), a compound found in Piper longum, has shown promise as a potential chemotherapeutic agent for breast cancer. However, its inherent toxicity has limited its application. To overcome this challenge, researchers have developed PIP@MIL-100(Fe), an organic metal–organic framework (MOF) that encapsulates PIP for breast cancer treatment. Nanotechnology offers further treatment options, including the modification of nanostructures with macrophage membranes (MM) to enhance the evasion of the immune system. In this study, the researchers aimed to evaluate the potential of MM-coated MOFs encapsulated with PIP for breast cancer treatment. They successfully synthesized MM@PIP@MIL-100(Fe) through impregnation synthesis. The presence of MM coating on the MOF surface was confirmed through SDS-PAGE analysis, which revealed distinct protein bands. Transmission electron microscopy (TEM) images demonstrated the existence of a PIP@MIL-100(Fe) core with a diameter of around 50 nm, surrounded by an outer lipid bilayer layer measuring approximately 10 nm in thickness. Furthermore, the researchers evaluated the cytotoxicity indices of the nanoparticles against various breast cancer cell lines, including MCF-7, BT-549, SKBR-3, and MDA. The results demonstrated that the MOFs exhibited between 4 and 17 times higher cytotoxicity (IC50) in all four cell lines compared to free PIP (IC50 = 193.67 ± 0.30 µM). These findings suggest that MM@PIP@MIL-100(Fe) holds potential as an effective treatment for breast cancer. The study’s outcomes highlight the potential of utilizing MM-coated MOFs encapsulated with PIP as an innovative approach for breast cancer therapy, offering improved cytotoxicity compared to free PIP alone. Further research and development are warranted to explore the clinical translation and optimize the efficacy and safety of this treatment strategy.

Synthesis, characterization, in-silico and in-vitro anticancer studies of Plumbagin encapsulated albumin nanoparticles for breast cancer treatment

Synthesis, characterization, in-silico and in-vitro anticancer studies of Plumbagin encapsulated albumin nanoparticles for breast cancer treatment

Evaluation of the parameters affecting the loading of anticancer drug Paclitaxel on coated gold nanoparticles for breast cancer treatment.

The purpose of this study is the design and synthesis of gold nanoparticles (GNPs) conjugated with paclitaxel and to investigate the parameters affecting the stability of synthesised nanoparticles with drug delivery capability. Here, synthesised GNPs were coated with polyethylene glycol. Then these particles were conjugated with paclitaxel under different conditions and the physical and structural characteristics, as well as the factors affecting the loading of paclitaxel on nanoparticles, were evaluated by ultraviolet spectrophotometer, fourier transform infraredspectroscopy, transmission electron microscopy, dynamic light scattering and zeta potential apparatus. It was found that pegylated GNPs have a limited loading capacity at the time of 24h of incubation and the Paclitaxel loading was observed to be pH dependent. The use of these particles in the treatment of breast cancer (MCF7) was also investigated using the MTT test. It was determined that the survival percentage of MCF7 cells in the presence of paclitaxel-bound nanoparticles decreases to about 55% at the maximum measured concentration (690μM).

Biomimetic Targeted Theranostic Nanoparticles for Breast Cancer Treatment.

The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer.

Smart Nanoparticles for Breast Cancer Treatment Based on the Tumor Microenvironment.

Breast cancer (BC) is the most common malignant tumor in women. There are different risk characteristics and treatment strategies for different subtypes of BC. The tumor microenvironment (TME) is of great significance for understanding the occurrence, development, and metastasis of tumors. The TME plays an important role in all stages of BC metastasis, immune monitoring, immune response avoidance, and drug resistance, and also plays an important role in the diagnosis, prevention, and prognosis of BC. Smart nanosystems have broad development prospect in the regulation of the BC drug delivery based on the response of the TME. In particular, TME-responsive nanoparticles cleverly utilize the abnormal features of BC tissues and cells to achieve targeted transport, stable release, and improved efficacy. We here present a review of the mechanisms underlying the response of the TME to BC to provide potential nanostrategies for future BC treatment.

Combinatorial Delivery of Gallium (III) Nitrate and Curcumin Complex-Loaded Hollow Mesoporous Silica Nanoparticles for Breast Cancer Treatment.

The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body’s circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3β(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy.

Abstract PO-216: Design, fabrication, and evaluation of dual-loaded biodegradable nanoparticles for breast cancer treatment

Abstract Introduction: The purpose of this study was to design, fabricate and determine the cytotoxic effects of dual-loaded (paclitaxel and 17-AAG) stealth polymeric nanoparticles. HSP90 inhibitors, such as 17-AAG, sensitize lung and breast cancer cells to paclitaxel induced cytotoxicity both in vitro and in vivo. Concurrent exposure to 17-AAG and paclitaxel is required for the synergistic activity of the two drugs. Further, clinical evaluations of 17-AAG in combination with approved therapies such trastuzumab and other drugs have shown enhancement or synergistic effects. Stealth nanoparticles are capable of providing site-specific tumor targeting thereby reducing toxicity in healthy cell, improving the solubility of anticancer drugs and synchronizing the disposition of encapsulated drugs (varying biodistribution/pharmacokinetics of combination drugs through cocktail administration has been attributed to their ineffectiveness in the clinic). Further, therapeutic nanoparticles could overcome drug resistance due to P-glycoprotein efflux pump. The stealth property of nanoparticles (PEG on the surface) will prevent capture by the reticuloendothelial system (RES) and will facilitate tethering ligands (mAbs) to the surface of the nanoparticles for receptor mediated endocytosis (active targeting). Dose reduction coupled with a better quality of life during treatment would also improve patient compliance. Experimental Procedures: A central composite face-centered statistical experimental design (CCF) in three independent factors and seventeen runs was implemented for the fabrication nanoparticles by dispersion polymerization technique using biodegradable poly-ϵ-caprolactone and a pH (acid) sensitive crosslinker, followed by computer optimizations. Numerical and graphical optimizations were carried out to select the factor combination to minimize the particle size, to minimize the time (h) for maximum release of paclitaxel and 17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximize paclitaxel and 17-AAG encapsulation efficiency. The optimal formulation was used for nanoparticle fabrication for biological studies in SKBR3 cell line (HER-2- overexpressing human breast cancer cell line) and MCF7 cell line (human breast cancer cell line). Results and Conclusion: The dispersion polymerization method was successfully used to fabricate an optimized dual-loaded nanoparticle formulation using an acid (pH) sensitive crosslinker and a macromonomer. The cytotoxic effects of the paclitaxel treatment and that of the drug combination (free drugs or nanoparticles) observed were similar in both SKBR3 and MCF7 cell lines suggesting synergistic or potentiation effects. Also, since paclitaxel and 17-AAG in the combination were half their concentrations, when used alone, and still yielded similar cytotoxic effects, we have been able to reduce the dose of paclitaxel without lowering its therapeutic efficacy. 17AAG on its own was not as effective as paclitaxel. Citation Format: Emmanuel O. Akala. Design, fabrication, and evaluation of dual-loaded biodegradable nanoparticles for breast cancer treatment [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-216.

Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving “on-demand” drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed in vitro experiments, it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic. Consequently, GNP-DOX/ICG could efficiently suppress the growth of 4T1 tumor in vivo. In conclusion, this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

In this investigation, a smart nanocarrier-loaded docetaxel, a microtubules disrupting agent and vorinostat, a histone deacetylase inhibitor was developed to achieve a synergistic anticancer effect. Dual drug-loaded lipid polymer hybrid nanoparticles were prepared, with easy fabrication and favorable properties including small size, narrow distribution and a high loading efficacy. The in vitro drug release conducted in phosphate-buffered saline, pH 7.4 and acetate-buffered saline, pH 5.5 media demonstrated the sustained, pH-dependent release profile. The nanoparticles were effectively taken up by cells, which ensured greater suppression of cell growth. The co-delivery of both drugs exhibited a synergistic effect on the induction of cancer cell apoptosis, resulting in greater inhibition of SCC-7, MCF-7, and MDA-MB-231 cancer cells by the drug-loaded carrier. These promising results may lead to clinical applications with enhanced docetaxel activity.

Combination of a chemopreventive agent and paclitaxel in CD44-targeted hybrid nanoparticles for breast cancer treatment.

The CD44 receptor, which is upregulated in many cancer cells, provides a selective cellular surface for targeted drug delivery systems. We developed a hybrid nanocarrier for the CD44-targeted delivery of ibuprofen (IBU) and paclitaxel (PTX). The solid lipid nanoparticles (SLNs) were prepared by a hot-melt oil/water emulsion technique and then coated with hyaluronic acid (HA) by electrostatic interactions. The final SLN were spherical with a hydrodynamic diameter (Z) of 72.16±2.9nm, polydispersity index (PDI) of 0.276±0.009, and zeta potential (ZP) of 28.20±0.69mV. Similarly, SLN coated with HA (SLN-HA) exhibited acceptable physical properties (Z 169.3±0.55nm, PDI 0.285±0.004, and ZP -10.5±0.15mV). Cell viability assays showed that the combination of IBU, a chemopreventive agent, and PTX exerted a synergistic inhibitory effect on the proliferation of cancer cells (CI <1.0). Additionally, our observations indicated that both SLN and SLN-HA enhanced apoptosis and cellular uptake compared to the cocktail of free drugs. HA indicated its affinity for cancer cells through the improvement of cellular uptake and induction of apoptosis. These results clearly indicated that these nanoparticle systems hold great promise for drug delivery in breast cancer treatment.

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake.

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising tools for the treatment of different diseases. Their magnetic properties enable therapies involving magnetic drug targeting (MDT), hyperthermia or imaging. Depending on the intended treatment, specific characteristics of SPIONs are required. While particles used for imaging should circulate for extended periods of time in the vascular system, SPIONs intended for MDT or hyperthermia should be accumulated in the target area to come into close proximity of, or to be incorporated into, specific tumor cells. In this study, we determined the impact of several accurately characterized SPION types varying in size, zeta potential and surface coating on various human breast cancer cell lines and endothelial cells to identify the most suitable particle for future breast cancer therapy. We analyzed cellular SPION uptake, magnetic properties, cell proliferation and toxicity using atomic emission spectroscopy, magnetic susceptometry, flow cytometry and microscopy. The results demonstrated that treatment with dextran-coated SPIONs (SPIONDex) and lauric acid-coated SPIONs (SPIONLA) with an additional protein corona formed by human serum albumin (SPIONLA-HSA) resulted in very moderate particle uptake and low cytotoxicity, whereas SPIONLA had in part much stronger effects on cellular uptake and cellular toxicity. In summary, our data show significant dose-dependent and particle type-related response differences between various breast cancer and endothelial cells, indicating the utility of these particle types for distinct medical applications.

Co-delivery of doxorubicin and pH-sensitive curcumin prodrug by transferrin-targeted nanoparticles for breast cancer treatment.

The natural product curcumin and the chemotherapeutic agent doxorubicin have been used in the treatment of many cancers, including breast cancer. However, fast clearance and unspecific distribution in the body after intravenous injection are still challenges to be overcome by an ideal nano-sized drug delivery system in cancer treatment. In this study we design transferrin (Tf) decorated nanoparticles (NPs) to co-deliver CUR and DOX for breast cancer treatment. A pH-sensitive prodrug, transferrin-poly(ethylene glycol)-curcumin (Tf-PEG-CUR), was synthesized and used for the self‑assembling of NPs (Tf-PEG-CUR NPs). DOX is incorporated into the Tf-PEG-CUR NPs to obtain Tf-PEG-CUR/DOX NPs. Invitro cytotoxicity studies and in vivo antitumor activity were carried out using MCF-7 cells and mice bearing MCF-7 cells, respectively. Tf-PEG-CUR/DOX NPs has a particle size of 89nm and a zeta potential of -15.6mV. This system displayed remarkably higher efficiency than other systems both invitro and invivo. DOX and CUR were successfully loaded into nanocarriers. The in vitro cell viability assays revealed the combination of Tf-PEG-CUR and DOX NPs exhibited higher cytotoxicity in vitro in MCF-7 cells compared with Tf-PEG-CUR NPs alone. Using the breast cancer xenograft mouse model, we demonstrate that this co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and exhibited stronger antitumor effect.

Docetaxel-Chitosan nanoparticles for breast cancer treatment: cell viability and gene expression study.

Docetaxel acts through the inhibition of tubulin polymerization and reduction in the expression of BCL-2 gene. In this study, nanoparticles containing Docetaxel were prepared and their effects on the gene expression levels of BCL-2 and BAX genes were investigated. The drug was first conjugated to chitosan, and the nanoparticles were assembled in the presence of hyaluronic acid. Conjugations were confirmed by 1 H-NMR, and the obtained nanoparticles were characterized by dynamic light scattering and SEM. Cytotoxicity of the nanoparticles, cellular uptake, and cell death were evaluated. Finally, the effect of nanoparticles on the expression of BAX and BCL-2 genes in MCF-7 cells were investigated through real-time PCR. The results revealed that the prepared NPs had spherical shape with narrow size distribution of <200nm with positive zeta potentials. In vitro cytotoxicity of Cs nanoparticles and free Docetaxel investigations revealed that increasing the treatment time with nanoparticles led to decrease in the rate of cell viability. BAX and BCL-2 gene expressions were decreased in nanoparticle-treated cells in comparison with intact cells, while the BAX/BCL-2 ratio was significantly elevated compared with free drug-treated cells after 72h. Docetaxel-conjugated NPs may offer a promising treatment with low off-target toxicity for breast cancer.

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

Co-delivery of docetaxel and Poloxamer 235 by PLGA-TPGS nanoparticles for breast cancer treatment.

Multidrug resistance (MDR) is a major hurdle to the success of cancer chemotherapy. Poloxamers have been shown to reverse MDR by inhibiting the P-glycoprotein (P-gp) pump. The objective of this research is to test the feasibility of docetaxel-loaded PLGA-TPGS/Poloxamer 235 nanoparticles to overcome MDR in docetaxel-resistant human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by a modified nanoprecipitation method using PLGA-TPGS and PLGA-TPGS/Poloxamer 235 mixture, respectively. The PLGA-TPGS/Poloxamer 235 nanoparticles were of spherical shape and have a rough and porous surface. The docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles which had an average size of around 180nm with a narrow size distribution were stable, showing almost no change in particle size and surface charge during the 3-month storage period. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PLGA-TPGS/Poloxamer 235 porous nanoparticles (PPNPs) in docetaxel-resistant human breast cancer cell line, MCF-7/TXT, in comparison with PLGA-TPGS nanoparticles (PTNPs). The PLGA-TPGS/Poloxamer 235 porous nanoparticles produced significantly higher level of toxicity than both of PLGA-TPGS nanoparticle formulation and Taxotere® both in vitro and in vivo, indicating docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles have significant potential for the treatment of breast cancer.

Multistage delivery of chemotherapeutic nanoparticles for breast cancer treatment

Adequate drug delivery to tumors is hindered by barriers such as degradation and non-specific distribution. Nested incorporation of drug-containing nanoparticles within mesoporous silicon particles (MSVs), carriers rationally designed to enhance tumor transport, was hypothesized to result in pronounced and sustained antitumor efficacy. Paclitaxel (PTX)-containing poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) polymer micelles were favorably loaded within MSVs, after which drug release was significantly delayed. Antitumor efficacy analyses in mice bearing MDA-MB-468 breast tumors demonstrated significant tumor growth suppression following a single administration. Results highlight effective chemotherapeutic shuttling and site-specific controlled release afforded by MSVs, potentially translating towards improvements in patient outcomes and morbidity.