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Infection and Drug Resistance 2024Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with...
INTRODUCTION
Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with HIV/AIDS (PWHA). PWHA with advanced immunosuppression who initiate antiretroviral therapy are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS).
CASE PRESENTATION
This report covers the case of a 25-year-old male with AIDS-related KS who relapsed after Liposomal Doxorubicin, but recovered well after administration of nab-paclitaxel (Nab-PTX).
CONCLUSION
This is a rare case in choosing Nab-PTX to treat relapsed AIDS-KS and get good feedback. We report the case to provide a possible solution to treat AIDS-KS.
PubMed: 38623529
DOI: 10.2147/IDR.S456286 -
ACS Applied Materials & Interfaces Apr 2024Bubble-enhanced shock waves induce the transient opening of the blood-brain barrier (BBB) providing unique advantages for targeted drug delivery of brain tumor therapy,...
Bubble-enhanced shock waves induce the transient opening of the blood-brain barrier (BBB) providing unique advantages for targeted drug delivery of brain tumor therapy, but little is known about the molecular details of this process. Based on our BBB model including 28 000 lipids and 280 tight junction proteins and coarse-grained dynamics simulations, we provided the molecular-level delivery mechanism of three typical drugs for the first time, including the lipophilic paclitaxel, hydrophilic gemcitabine, and siRNA encapsulated in liposome, across the BBB. The results show that the BBB is more difficult to be perforated by shock-induced jets than the human brain plasma membrane (PM), requiring higher shock wave speeds. For the pores formed, the BBB exhibits a greater ability to self-heal than PM. Hydrophobic paclitaxel can cross the BBB and be successfully absorbed, but the amount is only one-third of that of PM; however, the absorption of hydrophilic gemcitabine was almost negligible. Liposome-loaded siRNAs only stayed in the first layer of the BBB. The mechanism analysis shows that increasing the bubble size can promote drug absorption while reducing the risk of higher shock wave overpressure. An exponential function was proposed to describe the relation between bubble and overpressure, which can be extended to the experimental microbubble scale. The calculated overpressure is consistent with the experimental result. These molecular-scale details on shock-assisted BBB opening for targeted drug delivery would guide and assist experimental attempts to promote the application of this strategy in the clinical treatment of brain tumors.
PubMed: 38622933
DOI: 10.1021/acsami.4c00812 -
International Journal of Molecular... Mar 2024The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses...
The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4 and CD8 T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.
Topics: Animals; Mice; Exosomes; CD8-Positive T-Lymphocytes; Drug Delivery Systems; Biocompatible Materials; Disease Models, Animal; Paclitaxel; Neoplasms
PubMed: 38612457
DOI: 10.3390/ijms25073645 -
ACS Applied Bio Materials May 2024There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted...
There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted chemotherapeutic drugs has always been one of the main techniques. This work aims to develop a polycaprolactone/chitosan electrospun mat incorporated with paclitaxel/FeO-loaded niosomes (SPNs) decorated with trastuzumab (TbNs) for cancer therapy. SPNs and TbNs were analyzed by DLS, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. Fabricated mats with distinct concentrations of TbNs were classified into four groups (G0 (0), G1 (1), G2 (2.5), and G3 (5%)) and were studied physicochemically, mechanically, and biologically. Paclitaxel release was also studied for 7 days under an alternative magnetic field (AMF). The optimized mat was nominated for an in vivo study to evaluate its tumor growth inhibition. Based on the results, the TbNs had a spherical core and shell morphology with a smooth surface. The zeta potential and the mean size of TbNs were equal to -14.7 mV and 221 nm. TbNs did not affect the morphology and quality of nanofibers, but in general, the presence of TbNs increased the elastic modulus, water uptake, and degradation. Regarding the release study, AMF showed a significant increase in accelerating paclitaxel release from mats, and most releases belonged to the mat with 5% of TbNs. Results from the in vivo study showed the effective and synergistic effects of AMF on drug release and significant tumor growth inhibition. To summarize, the proposed nanocarrier under AMF can be a good candidate for cancer therapy.
Topics: Paclitaxel; Trastuzumab; Breast Neoplasms; Female; Animals; Humans; Particle Size; Materials Testing; Mice; Liposomes; Polyethylene Glycols; Biocompatible Materials; Drug Screening Assays, Antitumor; Cell Proliferation; Drug Carriers; Antineoplastic Agents; Mice, Inbred BALB C; Drug Delivery Systems; Cell Survival
PubMed: 38602218
DOI: 10.1021/acsabm.4c00027 -
AAPS PharmSciTech Apr 2024Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has risen, particularly in light of the recent COVID-19 pandemic. Conventionally, IPF is treated with antifibrotic drugs-pirfenidone and nintedanib-along with other drugs for symptomatic treatments, including corticosteroids, immunosuppressants, and bronchodilators based on individual requirements. Several drugs and biologicals such as fluorofenidone, thymoquinone, amikacin, paclitaxel nifuroxazide, STAT3, and siRNA have recently been evaluated for IPF treatment that reduces collagen formation and cell proliferation in the lung. There has been a great deal of research into various treatment options for pulmonary fibrosis using advanced delivery systems such as liposomal-based nanocarriers, chitosan nanoparticles, PLGA nanoparticles, solid lipid nanocarriers, and other nanoformulations such as metal nanoparticles, nanocrystals, cubosomes, magnetic nanospheres, and polymeric micelles. Several clinical trials are also ongoing for advanced IPF treatments. This article elaborates on the pathophysiology of IPF, its risk factors, and different advanced drug delivery systems for treating IPF. Although extensive preclinical data is available for these delivery systems, the clinical performance and scale-up studies would decide their commercial translation.
Topics: Humans; Pandemics; Idiopathic Pulmonary Fibrosis; Lung; Drug Delivery Systems; Pyridones; Nanoparticles
PubMed: 38589751
DOI: 10.1208/s12249-024-02793-y -
Therapeutic Advances in Medical Oncology 2024The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan (ONIVYDE)... (Review)
Review
The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan (ONIVYDE) stands out as the only drug that has demonstrated improved survival both as a first-line therapy in combination with oxaliplatin and 5-fluorouracil/leucovorin (5FU/LV) (NALIRIFOX) compared to the standard gemcitabine plus nab-paclitaxel in the NAPOLI3 trial, and as a second-line treatment in combination with 5FU/LV compared to the standard 5FU/LV in the NAPOLI1 trial. However, just as the white bear of the Dostoevsky's paradox, the judgment of these results is invariably distracted by the intrusive thought of how different they might be if compared to similar regimens containing standard-free irinotecan as FOLFIRINOX or FOLFIRI, respectively. Here, we present and thoroughly discuss the evidence encompassing the pharmacologic, preclinical, and clinical development of liposomal irinotecan that can dispel any intrusive thoughts and foster a rational and well-considered judgment of this agent and its potential integration into the therapeutic strategies for pancreatic ductal adenocarcinoma.
PubMed: 38584763
DOI: 10.1177/17588359241234487 -
Pancreatology : Official Journal of the... Jun 2024Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to...
BACKGROUND/OBJECTIVES
Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study.
METHODS
In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups.
RESULTS
The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02).
CONCLUSIONS
The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.
Topics: Humans; Pancreatic Neoplasms; Leucovorin; Middle Aged; Male; Female; Fluorouracil; Aged; Irinotecan; Tegafur; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Retrospective Studies; Oxonic Acid; Liposomes; Treatment Outcome; Neoplasm Metastasis; Adult; Paclitaxel
PubMed: 38565467
DOI: 10.1016/j.pan.2024.03.014 -
International Journal of Nanomedicine 2024The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in...
INTRODUCTION
The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvβ3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects.
METHODS
LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice.
RESULTS
The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers.
CONCLUSION
The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers.
Topics: Animals; Mice; Humans; Female; Ovarian Neoplasms; Liposomes; Receptors, LHRH; Integrin alphaVbeta3; Cell Line, Tumor; Mice, Nude; Paclitaxel; Oligopeptides
PubMed: 38562611
DOI: 10.2147/IJN.S442921 -
Drug Delivery Dec 2024Annonaceous acetogenins (ACGs) have potent anti-tumor activity, and the problems of their low solubility, hemolysis, and delivery have been solved by encapsulation into...
Annonaceous acetogenins (ACGs) have potent anti-tumor activity, and the problems of their low solubility, hemolysis, and delivery have been solved by encapsulation into nanoparticles. However, the high toxicity still limits their application in clinic. In this paper, the co-delivery strategy was tried to enhance the anti-tumor efficacy and reduce the toxic effects of ACGs. Ginsenoside Rh2, a naturally derived biologically active compound, which was reported to have synergistic effect with paclitaxel, was selected to co-deliver with ACGs. And due to its similarity with cholesterol in chemical structure, the co-loading liposomes, (ACGs + Rh2)-Lipo, were successfully constructed using Rh2 instead of cholesterol as the membrane material. The obtained (ACGs + Rh2)-Lipo and ACGs-Lipo had similar mean particle size (about 80 nm), similar encapsulation efficiency (EE, about 97%) and good stability. The MTS assay indicated that (ACGs + Rh2)-Lipo had stronger toxicity . In the study, in contrast to ACGs-Lipo, (ACGs + Rh2)-Lipo demonstrated an improved tumor targetability (3.3-fold in relative tumor targeting index) and significantly enhanced the antitumor efficacy (tumor inhibition rate, 72.9 ± 5.4% vs. 60.5 ± 5.4%, < .05). The body weight change, liver index, and spleen index of tumor-bearing mice showed that Rh2 can attenuate the side effects of ACGs themselves. In conclusion, (ACGs + Rh2)-Lipo not only alleviated the toxicity of ACGs to the organism, but also enhanced their anti-tumor activity, which is expected to break through their bottleneck.
Topics: Mice; Animals; Acetogenins; Liposomes; Glioma; Cholesterol; Ginsenosides
PubMed: 38555735
DOI: 10.1080/10717544.2024.2324716 -
Carbohydrate Polymers Jun 2024A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to...
A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to enhance oral delivery of paclitaxel (PTX) by targeting monocarboxylate transporters (MCT) and glucose transporters (GLUT). The synthesized NSCF was characterised by FT-IR and H NMR spectra. The prepared 30.78 % (degree of substitution of N-SAA) NSCF-PTX-PLip were approximately 150 nm in size, with a regular spherical shape, the zeta potential of -25.4 ± 5.13 mv, drug loading of 2.35 % ± 0.05 %, and pH-sensitive and slow-release characteristics. Compared with PTX-Lip, 30.78 % NSCF-PTX-PLip significantly enhanced Caco-2 cellular uptake via co-mediation of MCT and GLUT, showing relatively specific binding of propionic acid and MCT. Notably, the NSCF modification of PTX-Lip had no appreciable influence on their original cellular uptake pathway. The fructose modification of 30.78 % NSC-PTX-PLip significantly increased the concentration after t, indicating their continuous and efficient absorption. Compared with PTX-Lip, the 30.78 % NSCF-PTX-PLip resulted in a 2.09-fold extension of MRT, and a 6.06-fold increase of oral bioavailability. It significantly increased tumour drug distribution and tumour growth inhibition rate. These findings confirm that 30.78 % NSCF-PLip offer a potential oral delivery platform for PTX and targeting the dual transporters of MCT and GLUT is an effective strategy for enhancing the intestinal absorption of drugs.
Topics: Humans; Paclitaxel; Liposomes; Caco-2 Cells; Spectroscopy, Fourier Transform Infrared; Fructose; Drug Delivery Systems; Antineoplastic Agents, Phytogenic
PubMed: 38553209
DOI: 10.1016/j.carbpol.2024.121989