Weekly intravenous nanoparticle albumin-bound paclitaxel for elderly patients with stage IV non-small-cell lung cancer:a series of 20 cases

The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.

Hemorrhagic cystitis in gastric cancer after nanoparticle albuminbound paclitaxel:A case report

BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.

Paclitaxel and curcumin co-bound albumin nanoparticles having antitumor potential to pancreatic cancer

Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Nucleobase-crosslinked poly(2-oxazoline) nanoparticles as paclitaxel carriers with enhanced stability and ultra-high drug loading capacity for breast cancer therapy

Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties.The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers,however,tend to be insufficient.Herein,we report a strategy to prepare nucleobase-crosslinked POx nanoparticles(NPs)with enhanced stability and ultra-high paclitaxel(PTX)loading capacity for breast cancer therapy.An amphiphilic amine-functionalized POx(PMBEOx-NH_(2))was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly(2–butyl–2-oxazoline-co-2-butenyl-2-oxazoline)(PMBEOx).Complementary nucleobase-pairs adenine(A)and uracil(U)were subsequently conjugated to PMBEOx-NH2 to give functional POxs(POxA and POxU),respectively.Due to the nucleobase interactions formed between A and U,NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity(38.2%,PTX/POxA@U),excellent stability,and reduced particle size compared to the uncross-linked PTX-loaded NPs(PTX/PMBEOx).Besides the prolonged blood circulation and enhanced tumor accumulation,the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx,thus leading to a higher tumor suppression rate in two murine breast cancer models(E0711 and 4T1).These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.

Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles： a magnetic resonance imaging study

Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel （4 mg/kg） while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area （14%） and stenosis （22%） by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report

BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors.Most patients have advanced-stage or unresectable disease at presentation,and the systemic therapies have limited efficacy.Albumin-bound paclitaxel(nab-paclitaxel)is a solvent-free taxane that has been approved for the treatment of some cancers such as breast,non-small cell lung and pancreatic cancer,however it has not been applied to treat cholangiocarcinoma.We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma,yet no phase 3 trials have been made.CASE SUMMARY A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma.Surgery was performed,followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine;although,the gemcitabine was suspended due to allergic reaction after two cycles.In April 2019,metastatic cholangiocarcinoma relapse was diagnosed,and a first-line treatment with FOLFOX scheme was started.Eight cycles were administered,producing an initial clinical improvement and decrease in blood tumor marker levels.Radiological and serological progression was noted in September 2019.As a second-line treatment,FOLFIRI was not recommended due to risk of worsening the patient’s tumor-related diarrhea.A combination therapy with gemcitabine was not feasible,as the patient had previously suffered from an allergic reaction to this treatment.We decided to use nab-paclitaxel as a second-line treatment,and four cycles were administered.Both clinical and serological responses were observed,and a radiological mixed response was also noted.CONCLUSION Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy,which should be studied in combination with other types of treatment(chemotherapy,fibroblast growth factor receptor inhibitors).

Short-term outcomes of albumin-bound paclitaxel (abraxane)-containing chemotherapy in patients with advanced gastric cancer: a report of 14 cases

Objective： Albumin-bound paclitaxel （abraxane, ABX） has more favorable efficacy and less toxicity than conventional taxanes. However, the data of ABX in advanced gastric cancer （AGC） treatment is unavailable. The current study was designed to summarize our experience in treating AGC patients with ABX. Methods： The clinical data of patients with AGC who had received at least one cycle of ABX-based chemotherapy in Sun Yat-sen University Cancer Center from January 10th 2010 to May 14th 2012 was retrospectively analyzed. Results： A total of 47 cycles of ABX-containing regimens, with a median of 3 cycles （range： 1-8 cycles）, were administered to 14 patients. Five （35.7%） partial responses and 6 （42.9%） stable diseases were obtained, with a disease control rate （DCR） of 78.6%. The median progression free survival （PFS） and overall survival （OS） were 3.3 and 10.8 months, respectively. Interestingly, patients in the first-line setting achieved a DCR of 100% （8/8）. Neutropenia and thrombocytopenia were the main grade 3/4 adverse events with an incidence of 50% in the whole group. However, only 25% patients （2/8） experienced grade 3 neutropenia when ABX in combination with fluoropyrJmJdines. Conclusion： The activity of ABX-based regimens as first-line therapy for patients with AGC is remarkable, and the toxicity is mild when ABX combined with fluorepyrimidines. Further prospective clinical trials of ABX-based chemotherapy as first-line treatment for AGC are strongly anticipated.

负载紫杉醇和JAK2-STAT3抑制剂纳米载药系统对胃癌细胞生物活性的影响机制研究

目的研讨负载紫杉醇和JAK2-STAT3抑制剂纳米载药系统对胃癌细胞生物活性的抑制作用。方法选取胃癌细胞GBC-SD为研究对象,构建PLGA(TAXOL+AZD1480)纳米粒子,确定粒子的稳定性及释放药物速率稳定性;比较对照组、PLGA组、TAXOL+AZD1480组、PLGA(TAXOL+AZD1480组)各组胃癌细胞JAK2-STAT3信号通路活性、增殖、凋亡、迁移、侵袭能力。结果PLGA(TAXOL+AZD1480)纳米粒子120 h内呈现出缓慢、稳定释放;TAXOL+AZD1480组及PLGA(TAXOL+AZD1480)组JAK2、STAT3磷酸化蛋白水平均降低(P<0.05);与PLGA组相比,TAXOL组、AZD1480组均可以下调胃癌细胞增殖、迁移、侵袭能力,上调细胞凋亡能力,Cyclin D1、MMP-9蛋白表达受到抑制,Cleaved-caspase-3、Bax蛋白表达提升(P<0.05);与TAXOL组、AZD1480组相比,TAXOL+AZD1480组、PLGA(TAXOL+AZD1480)组进一步下调胃癌细胞增殖、迁移、侵袭能力,上调凋亡能力(P<0.05);TAXOL+AZD1480组、PLGA(TAXOL+AZD1480)组两组癌细胞增殖、凋亡、迁移、侵袭活性相近(P>0.05)。结论本研究成功构建了共载TAXOL和AZD1480的PLGA(TAXOL+AZD1480)载药传递系统,该纳米体系具有药物缓释以及抑制胃癌的作用,药效确切,值得在临床进一步推广。

基于真实世界数据的注射用紫杉醇(白蛋白结合型)药学监护路径研究

目的:建立注射用紫杉醇(白蛋白结合型)(nab-PTX)药学监护路径,为临床合理用药提供参考。方法:对2020年1月至2023年6月该院使用过nab-PTX的患者资料进行回顾性分析,评价用药合理性。以nab-PTX的药品说明书为基础,以循证医学为依据,结合该院nab-PTX使用的真实世界数据等,建立nab-PTX在肿瘤患者真实世界人群中合理用药的药学监护路径。结果:本研究纳入279例使用过nab-PTX的患者数据。分析结果显示,42例转移性乳腺癌患者符合nab-PTX的药品说明书适应证;超说明书适应证用药的共237例(占84.9%),其中有循证医学证据的超说明书适应证用药有209例(包括宫颈癌、胰腺癌、胃癌、非小细胞肺癌、鼻咽癌、卵巢癌或输卵管癌、食管癌、子宫内膜癌、胆管癌),评价为用药合理,而部分超说明书用药(口腔癌、纵隔恶性肿瘤、骨肿瘤、软组织恶性肿瘤、前列腺癌、十二指肠恶性肿瘤等)循证医学证据不足,评价为不合理用药。患者使用nab-PTX最常见的不良反应为骨髓抑制和周围神经病变,与药品说明书相符。在此基础上,从化疗前、化疗中、化疗后及随访等多方面建立了nab-PTX药学监护路径。结论:nab-PTX超说明书用药普遍存在,应加强对nab-PTX应用的管理,通过制定住院患者nab-PTX药学监护路径,可以提高药师的工作效率,保障肿瘤患者合理用药。

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile,acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1(PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps,we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer withmitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-bdual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase(AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugatingmitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembledwith albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticleseffectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation ofPTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-b in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cellinfiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy toinhibit PTX@Alb-resistant tumors, further supporting its better clinical application。

白蛋白紫杉醇术后辅助化疗乳腺癌患者预后的单中心回顾性队列研究

目的基于四川大学华西医院的乳腺癌临床队列,探讨乳腺癌患者术后辅助化学治疗(简称化疗)紫杉类药物的选择和预后。方法收集四川大学华西医院乳腺癌信息管理系统2018年1月至2020年3月1537例经组织学确诊乳腺癌患者的临床资料,治疗方案包括术前未行新辅助化疗、行乳腺癌根治术或保乳手术,术后接受含紫杉类药物辅助化疗。按化疗方案的不同分为3组,即白蛋白紫杉醇组(260 mg/m^(2)每3周1次或125 mg/m^(2)每周1次)147例,多西他赛组(100 mg/m^(2)每3周1次)1285例,紫杉醇组(80 mg/m^(2)每周1次)105例。采用Kaplan-Meier法进行生存分析,Cox比例风险回归分析进行多因素分析,并根据年龄、临床分期和激素受体状态进行倾向性评分匹配。结果年龄≤40岁患者的比例白蛋白紫杉醇组、多西他赛组、紫杉醇组分别为25.17%,20.39%,17.14%,且白蛋白紫杉醇组显著高于多西他赛组(P=0.046)和紫杉醇组(P=0.003);肿瘤直径≥2 cm患者的比例分别为64.63%,56.96%,65.71%,白蛋白紫杉醇组显著高于多西他赛组(P=0.042);淋巴结阳性比例分别为58.50%,46.77%,60.00%,组间差异显著(P<0.001),且白蛋白紫杉醇组显著高于多西他赛组(P=0.026)。中位随访时间为23个月。白蛋白紫杉醇组、多西他赛组、紫杉醇组的2年无病生存(DFS)率分别为96.00%,97.80%,94.80%,组间无显著差异(P=0.095)。Cox单因素分析结果显示,与多西他赛组相比,紫杉醇组的复发风险显著升高[HR=2.3,95%CI(1.1,4.9),P=0.04],而白蛋白紫杉醇组的复发风险无显著差异[HR=1.3,95%CI(0.4,3.5),P=0.66]。多西他赛组和白蛋白紫杉醇组按1∶4匹配,多西他赛组和紫杉醇组按1∶4匹配,白蛋白紫杉醇组和紫杉醇组按1∶1匹配,当校正T分期、N分期、雌激素受体状态、Ki67混杂因素后,仍未发现不同治疗组间DFS的差异(P=0.70,0.35,0.53)。结论相对于多西他赛,年龄≤40岁、肿瘤直径≥2 cm、淋巴结阳性患者更倾向于在辅助化疗中选择白蛋白紫杉醇。整体人群未发现白蛋白紫杉醇、多西他赛和紫杉醇辅助化疗对DFS的影响,尚需进一步长期随访。

Preparation, optimization and in vitro evaluation of core-shell paclitaxelloaded nanoparticles composed of MPEG-PLA and PLA

Nanoparticles with typical core-shell structure were prepared with a blend of methoxypoly（ethylene glycol）-poly（lactide） copolymer （MPEG-PLA） and poly （lactic acid） （PLA） along with paclitaxel by the O/W solvent evaporation method. An orthogonal experiment L9（3）3 was applied to get the best preparation conditions. The core-shell paclitaxel-loaded MPEG-PLA/PLA nanoparticles with the highest drug loading efficiency were obtained when amount of MPEG-PLA, time of ultrasonication and volume of deionized water were 300 mg, 10 rain and 30 mL, respectively. The release behavior of paclitaxel from the optimal MPEG-PLA/PLA nanoparticles showed that 22% ofpaclitaxel was released in 14 d. When incubating with human nasopharyngeal carcinoma ceils expressing LMP 1, these optimal nanoparticles showed a little lower tumor growth compared with free paclitaxel.

Hematological and pathological toxicity of anti-HER2/neu peptide mimetic modified paclitaxel bovine serum albumin nanoparticles

Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.

白蛋白紫杉醇临床应用及医保报销情况调查

目的:了解白蛋白紫杉醇(Nanoparticle Albumin Bound Paclitaxel,NAB-PTX)在医保患者中的临床使用以及报销情况,为NAB-PTX纳入医保支付后的报销管理提供参考。方法:结合《国家基本医疗保险、工伤保险和生育保险药品目录》(简称:《药品目录》),分析研究单位2021年9月至2022年2月NAB-PTX医保患者的临床使用及医保报销数据。对患者特征、疾病分布、药品用量、医保报销情况等进行描述性统计分析。采用Mann-Whiney U检验比较乳腺恶性肿瘤患者中NAB-PTX是否纳入报销对患者费用负担的影响。结果:医保患者使用NAB-PTX人次排名前三的疾病为乳腺恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤。215人次符合医保支付条件,占使用总人次的7.19%。乳腺恶性肿瘤患者使用NAB-PTX排名前三的情况为乳腺癌术后辅助化疗、乳腺癌术前新辅助治疗、联合化疗失败的转移性乳腺癌。NAB-PTX纳入报销的患者自付费用与NAB-PTX未纳入报销的患者差异较大。结论:NAB-PTX在恶性肿瘤的治疗中应用广泛,2021年《药品目录》报销的覆盖范围有限,2022年《药品目录》取消NAB-PTX支付适应症限定后需要结合药品集中带量采购政策做好药物经济学评价以及基金支出预算分析。

^(131)I标记贝伐单抗偶联载紫杉醇超顺磁性氧化铁纳米粒的制作及生物分布实验

为了研究^(131)I标记贝伐单抗偶联载紫杉醇超顺磁性氧化铁纳米粒(^(131)I-Bevacizumab-Paclitaxel-Superparamagnetic Iron Oxide Nanoparticles,^(131)I-BEV-PTX-SPIONs)的制备和生物学分布。将30只成瘤裸鼠分为单靶向组及双靶向组,再按时间点2 h、6 h、12 h、24 h及48 h分为5个亚组,每亚组各3只,尾静脉注射^(131)IBEV-PTX-SPIONs后,进行生物学分布及单光子发射计算机断层成像术(Single-Photon Emission Computed Tomography,SPECT)显像。^(131)I-BEV-PTX-SPIONs的粒径约220 nm,分散性尚可;^(131)I标记率为81.4%;放射性化学纯度(Radiochemical Purity,RCP)>99%;在PB缓冲液中稳定性良好;在体外PTX(Paclitaxel)缓释性能良好;与A549细胞有较好的亲和力。体内生物学分布结果:随着时间的延长,肿瘤组织的放射性计数相对增高,12 h达高峰;T/NT(Target to Nontarget)比值逐渐升高,48 h达7.80±0.50。6 h、12 h、24 h、48 h时,双靶向组的肿瘤组织放射性计数及T/NT比值均高于单靶向组,差异均具有统计学意义(P<0.05),且差异性随着时间延长越来越显著。SPECT显像结果:2 h肿瘤部位即有放射性聚集,且随着时间的延长,放射性聚集增加并持续稳定,T/NT比值持续上升。初步研究结果显示,^(131)I-BEV-PTX-SPIONs具有用于肺癌诊疗的潜质,值得进一步研究。

构建掺杂铕(Eu)的二氧化硅(SiO2)纳米粒子载药平台

目的构建掺杂铕(Eu)的中空介孔二氧化硅(SiO2)纳米粒子载药平台,并观察其特性。方法采用水热法制备掺杂Eu的SiO2空心微球,在其表面修饰靶向物质透明质酸(HA),以浸润法将紫杉醇(PTX)负载于介孔氧化硅纳米颗粒(MSN)中,得到HA-Eu-hMSNs-PTX,观察其形态、荧光特性等性状,以及载药量、生物安全性及细胞毒性。结果所获HA-Eu-hMSNs直径(61.33±8.94)nm;以PTX修饰后成功制备HA-Eu-hMSNs-PTX,其PTX负载量为52.33µg/mg。加入Eu-hMSNs和HA-Eu-hMSNs后,SW1990细胞的细胞核均被DAPI染为蓝色并可见红色荧光信号,但加入Eu-hMSNs后该信号较弱。加入HA-Eu-hMSNs 24 h后,最高浓度(200μg/ml)组SW1990细胞存活率仍在90%以上。PTX、Eu-hMSNs-PTX和HA-Eu-hMSNs-PTX均对SW1990细胞具有浓度依赖性细胞毒性;相同PTX浓度下,HA-Eu-hMSNs-PTX的细胞毒性高于游离PTX和Eu-hMSNs-PTX。结论所制备HA-Eu-hMSNs-PTX粒径均匀、生物安全性佳,靶向能力和肿瘤细胞杀伤能力良好。

经iRGD修饰胡桃醌-紫杉醇靶向纳米粒子的制备及其对人骨肉瘤细胞Saos-2的抑制作用

目的构建经iRGD修饰的胡桃醌(juglone,Jug)-紫杉醇(paclitaxel,PTX)靶向纳米粒子(nanoparticles,NPs),并评价其对人骨肉瘤细胞Saos-2的抑制作用。方法通过乳化法制备iRGD-PLGA-(Jug,PTX)-NPs,并评价其材料特性、载药能力和体外释放结果。利用荧光显微镜观察iRGD-PLGA-(Jug,PTX)-NPs体外细胞摄取情况,再通过MTT法比较各组对Saos-2细胞的增殖抑制作用。结果①在Jug:PTX=0.1 mg:0.1 mg,iRGD-PLGA=1 mg条件下,成功制备iRGD-PLGA-(Jug,PTX)-NPs。②透射电镜下可见,纳米粒子为大小均一的类球形,粒径为233.3 nm,Jug载药率为8.68%,包封率为31.87%,PTX载药率为8.98%,包封率为30.18%;③体外药物释放显示,前24 h中为突释,随后为缓释,96 h后Jug累积释放为(72.108±1.243)%,PTX为(69.980±3.626)%;④细胞摄取实验显示,iRGD修饰的纳米粒子较无修饰粒子进入细胞更多;⑤MTT结果显示,Jug和PTX均可抑制Saos-2细胞增殖,且呈现出剂量依赖性。药物处理24 h后,裸药组抑制率明显高于其他组,而在48 h后,iRGD-PLGA-(Jug,PTX)-NPs抑制率高于裸药组。结论iRGD-PLGA-(Jug,PTX)-NPs稳定性较好,包载药物表现出先突释后缓释的现象,iRGD修饰可增强肿瘤靶向穿透性,提升疗效。