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1.
J Biomed Nanotechnol ; 15(12): 2305-2320, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748013

RESUMO

Verteporfin photodynamic therapy (PDT) has been approved for the treatment of exudative age-related macular degeneration (AMD) for over a decade. However, its extensive application has been impeded by inevitably collateral tissue damage and immediate induction of angiogenesis, in addition to the need of multiple treatments. In order to develop prospective photosensitizers for clinical use, a triphenyl phosphonium-modified cationic liposomal hypocrellin B (TPP cationic LHB) for angiogenic targeting and endothelial internalization was constructed. With optimal PDT parameters, TPP cationic LHB can lead to death of choroid-retinal vascular endothelial cells while cause negligible damage to collateral retinal pigment epithelium cells. This is likely due to the mitochondria targeting and effective intracellular singlet oxygen generation of TPP cationic LHB in vascular endothelial cells. Additionally, in vivo chick chorioallantoic membrane assay indicated the elevated neovessel-targeting ability and photo-induced anti-angiogenic activity of TPP cationic LHB. Furthermore, TPP cationic LHB PDT is able to maintain neovessel occlusion for an extended period of time compared with verteporfin PDT, without inducing significant increased expression of some angiogenic factors, such as vascular endothelial growth factor and integrin αvß3. This study describes a facile strategy that may be useful for developing new-generation photosensitizers to circumvent the limitations of PDT treatment of exudative AMD.


Assuntos
Degeneração Macular , Perileno/análogos & derivados , Fotoquimioterapia , Quinonas/uso terapêutico , Animais , Neovascularização de Coroide , Células Endoteliais , Lipossomos , Degeneração Macular/tratamento farmacológico , Perileno/uso terapêutico , Fármacos Fotossensibilizantes , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular
2.
J Biomed Nanotechnol ; 15(12): 2413-2427, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748021

RESUMO

With aging of population, changing of living habits, and intake of high-fat diet, more and more people have been suffering from cardio-cerebral apoplexy. The synchronous treatment of cardio-cerebral conditions based on an integral strategy may bring benefit to the better clinical efficacy. The simultaneously-targeting delivery of active molecules by nanoscale carriers to heart and brain remains unmet problem. The physiological difference of targets between heart and brain makes it a huge challenge which one targeting ligand modification acquires the delivery of two organs and treatment, simultaneously. Traditionally, dually targeting strategies are introduced to enhance the selectivity for one aimed tissue and delivery efficiency of these particles. However, the interference between two targeting ligands on the surface of nanoscale carriers may influence the affinity of these ligands with their receptors or transporters, resulting to the change distribution of carriers. Herein, we observed that how anti-cardiac troponin I (cTnI) antibody (Ab) conjugated with the linker, polyethylene glycol (PEG), on the surface of liposomes influenced the affinity of mannose derivatives with transporter and regulated distribution of these vesicles in the heart and brain. The dually targeting liposomes can target to the heart and brain tissue simultaneously by the regulation length of PEG chain linking with p -pentanoic acid phenyl-α-D-acetylmannosamine (Ac4MAN). These results may bring benefit to design the multi-modification of nanocarriers and the treatment of cardio-cerebral diseases.


Assuntos
Lipossomos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Imunoconjugados , Ligantes , Manose , Polietilenoglicóis
3.
Phys Chem Chem Phys ; 21(45): 25054-25064, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31690919

RESUMO

Liposomes carrying membrane-embedded porphyrin-phospholipid (PoP) are capable of chemo- and photo-therapeutic modes of action, which make them a potential candidate material for next-generation cancer treatments. This study examines singlet oxygen (1O2) production and release by PoP liposomes carrying either no chemotherapeutic cargo (EMPTY), or those carrying either doxorubicin (DOX) or irinotecan (IRT) chemotherapy drugs. Herein, we developed a strategy to quantify the fraction of 1O2 lifetime spent in the three distinct local liposomal environments by obtaining four key pieces of information for each system: average 1O2 deactivation rate constants (kΔ) for liposome suspensions in H2O and in D2O solvents, as well as the absolute and the apparent 1O2 production quantum yields (ΦΔ). Despite the characteristic differences in their photophysical behavior, namely in ΦΔ values, all three formulations of PoP liposomes were found to carry out 1O2 release in a similar manner. It was found that >80% of all sensitized 1O2 from the ensemble of PoP liposomes deactivates within the nanostructures themselves, with the largest portion (∼50%) deactivating in the lipid membrane specifically. Based on these findings, we conclude that the current design of the PoP liposomes is well suited for light-induced chemotherapeutic drug release. Importantly, the 1O2 partition quantification approach reported herein has potential to be a tool for characterizing nanoparticulate light-activated chemo- and phototherapeutic systems.


Assuntos
Fosfolipídeos/química , Fotoquimioterapia , Oxigênio Singlete/química , Humanos , Lipossomos/química , Porfirinas/química
4.
J Photochem Photobiol B ; 200: 111645, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31671371

RESUMO

Antimicrobial peptide W3R6 was derived from chensinin-1b and showed potential as a novel antibiotics. However, W3R6 was susceptible to protease cleavage, which limited its therapeutic application. To improve the proteolytic resistance of W3R6, D-amino acids were incorporated into its sequence by specific amino acid substitution or whole sequence substitution according to the specificity of the cleavage site. In this study, partially substituted analog D-Arg-W3R6 and completely substituted D-enantiomer D-W3R6 were synthesized. The resistance of D-Arg-W3R6 and D-W3R6 to cleavage by the tested protease increased, particularly of D-W3R6. The antimicrobial activity of D-Arg-W3R6 was almost the same as that of the parent peptide W3R6, but the antimicrobial activity of D-W3R6 was slightly decreased. The hemolytic activity of both D-Arg-W3R6 and D-W3R6 was negligible. The CD spectrum of D-W3R6 exhibited symmetry with that of W3R6 in a membrane-mimetic environment. The membrane interaction between the D-amino acid substituted analogs and a real/mimic bacterial cell membrane was examined. The outer membrane depolarization, inner membrane permeability and dye leakage in three types of liposomes treated with D-Arg-W3R6 and D-W3R6 were not obviously different from W3R6, which could be due to the similar physical and chemical properties. In addition, these three peptides showed the binding ability with LPS micelles detected by ITC, and their ability to disrupt the LPS micelles was examined by DLS experiment and even neutralize the surface negative charge of E. coli cells. These results suggest that D-Arg-W3R6 is a promising antibiotic molecule.


Assuntos
Aminoácidos/química , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Parede Celular/química , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Lipossomos/química , Lipossomos/metabolismo , Peptídeos/química , Permeabilidade/efeitos dos fármacos , Estabilidade Proteica
5.
Biomed Khim ; 65(5): 374-379, 2019 Aug.
Artigo em Russo | MEDLINE | ID: mdl-31666408

RESUMO

Identification of new protein-protein interactions (PPI) and characterization of quantitative parameters of complex formation represent one of central tasks of protein interactomics. This work is a logical continuation of the cycle of our previous works devoted to the study of PPIs among the components of cytochrome P450-dependent monooxygenase system. Using an optical biosensor of Surface Plasmon Resonance (SPR biosensor), a comparative analysis on the determination of kinetic and equilibrium parameters of complex formation between the membrane-bound hemoprotein cytochrome b5 with cytochrome P450s was performed using two different protocols for protein immobilization: 1) covalent non-oriented one on to the carboxymethyl dextran chip type CM and 2) non-covalent oriented immobilization in the lipid environment on the chip type L1 with internal control of liposomes surface distribution. In the second protocol it was shown that the complex formation was characterized by 2.5 times higher affinity due to an decrease in rate dissociation constants. The appropriateness of using both experimental models is discussed.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Citocromos b5/metabolismo , Lipossomos/metabolismo , Mapeamento de Interação de Proteínas , Humanos , Cinética , Lipídeos , Ressonância de Plasmônio de Superfície
6.
Am Surg ; 85(9): 956-960, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638506

RESUMO

Postoperative pain managed with opioids has contributed to the opioid crisis through overprescribing practices. We assessed opioid-prescribing habits and their use by patients undergoing surgery for cutaneous malignancies. An Institutional Review Board-approved retrospective analysis was conducted for patients who underwent skin cancer resection between January 2018 and June 2018. Data were collected from the electronic medical record, and opioid-related data were collected from patient interviews and state registries. There were 120 study participants (42 females and 78 males) with a median age of 67 years (range, 21-94 years). All received preincision local anesthetic: 64 had liposomal bupivacaine (LB) (53%) and 56 had non-LB bupivacaine (47%). Most participants (n = 88) used 0 opioids (73%), including 43 LB-anesthetic (67%) and 45 non-LB-anesthetic (80%). No significance was seen between those with a diagnosis of chronic pain, narcotic tolerance, an area of resection, and nodal sampling groups in opioid use. Four patients (3%) requested a refill. Of 105 prescriptions written for opioids, 99 had leftover opioids for an overprescribing rate of 94 per cent. This study suggests pain after skin cancer surgery is manageable with very limited opioid requirements. Our results support prescribing no more than five opioid tablets for postoperative pain control in patients undergoing resection for skin malignancies.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Analgésicos Opioides/uso terapêutico , Prescrição Inadequada/estatística & dados numéricos , Dor Pós-Operatória/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Feminino , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Estudos Retrospectivos , Sudeste dos Estados Unidos , Adulto Jovem
7.
Am Surg ; 85(9): 1013-1016, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638516

RESUMO

Transversus abdominis plane (TAP) blocks are a safe and effective way to provide immediate postoperative pain relief in surgical patients, and have been shown to decrease narcotic requirements. Concerns about complications of narcotics, increase in hospital length of stay (LOS), and health-care costs make this of particular interest. We compared standard bupivacaine TAP blocks with those carried out using liposomal bupivacaine to evaluate postoperative outcomes. Fifty patients undergoing elective laparoscopic colectomy received laparoscopic liposomal bupivacaine TAP blocks using 80 cc of local anesthetic, and data were collected prospectively during hospitalization. Data collected included amount of narcotic medication used during hospitalization, number of days to ambulation, number of days to bowel function, and LOS. These patients were compared with the last 50 patients recruited to the control/bupivacaine TAP block arm of the study. The same data parameters were collected and all patients were on an enhanced recovery protocol, which included scheduled acetaminophen, ibuprofen, and gabapentin by mouth, as well as clear liquid diet starting on postoperative day zero. Statistical analysis was performed using Student's t test and Fisher's exact test; P < 0.05 was considered statistically significant. Patients treated with liposomal bupivacaine needed less narcotics (5.06 vs 18.75 mg, P = 0.0002), had earlier bowel function (1.7 vs 2.4 days, P = 0.0002), and shorter LOS (2.7 vs 3.4 days, P = 0.0146). Patients undergoing laparoscopic colon resections seem to require fewer narcotics and have better patient outcomes with liposomal bupivacaine TAP blocks. Based on our data, liposomal bupivacaine seems to be superior to bupivacaine for TAP blocks.


Assuntos
Músculos Abdominais/inervação , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Colectomia/efeitos adversos , Laparoscopia/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Tempo de Internação , Lipossomos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos
8.
Expert Opin Ther Pat ; 29(11): 891-907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603360

RESUMO

Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug delivery purposes have underlined that lately published patents (since 2014) are exploring alternative compositions and ways to optimize the stability and drug loading content/release profile. These improvements are complemented by improved long-circulating structures and further liposome functionalizations, which have definitively opened the road for the (co-)delivery of therapeutics to the site of action. Liposomes are also contributing to new drug delivery approaches involving the generation of extracellular vesicles by targeted cells, while opening new ways to combine disease diagnosis and therapy (theranosis). Expert opinion: Patent publications on liposomal formulations have expanded new ways in drug delivery. New lipid compositions and strategies to optimize stability and drug vehiculization capabilities have settle solid pillars in liposome fabrication. Despite, their architecture has been satisfactorily adapted for combining passive and active drug targeting concepts, new inputs of liposomes into the disease arena should answer for: a simple/scalable/cost-effective formulation; a safe/stable/controllable formulation meeting quality control regulations; and, a confirmed therapeutic efficiency in clinical investigations.


Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Lipídeos/química , Animais , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Lipossomos , Nanotecnologia/métodos , Patentes como Assunto
9.
J Cancer Res Clin Oncol ; 145(12): 2951-2967, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654121

RESUMO

PURPOSE: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide and new improvements are urgently needed. Several miRNA-targeted therapeutics have reached clinical development. MicroRNA-143 (miR-143) was found to significantly suppress the migration and invasion of NSCLC. It might be of great potential for NSCLC treatment. However, the therapeutic effect of miR-143 against NSCLC in vivo has not been explored until now. METHODS: The cationic liposome/pVAX-miR-143 complex (CL-pVAX-miR-143) was prepared and its biodistribution was assessed. The tumor suppression effects of CL-pVAX-miR-143 were evaluated in early-stage and advanced experimental lung cancer metastasis mice models by systemic delivery, respectively, and also in subcutaneous tumor models by intratumoral injection. The toxicity of CL-pVAX-miR-143 was assessed by H&E analysis and biochemical measurements. The preliminary mechanism of CL-pVAX-miR-143 on tumor suppression was explored by immunochemistry and western blotting. RESULTS: The assays on the stability and safety of CL-pVAX-miR-143 showed that it mainly accumulated in the lung after systemic administration. The intratumoral delivery of CL-pVAX-miR-143 effectively inhibited A549 subcutaneous tumor growth. Notably, systemic delivery of CL-pVAX-miR-143 significantly inhibited tumor metastasis and prolonged survival dose dependently in early-stage experimental lung cancer metastasis models. More importantly, same results were shown in advanced mice models with metastasis. CL-pVAX-miR-143 treatment did not induce obvious acute toxicity. The preliminary mechanism on inhibiting tumor metastasis might be induced by targeting CD44v3. CONCLUSIONS: Our results suggested that CL-pVAX-miR-143 might be a promising strategy for clinical treatment of non-small cell lung cancer, especially for advanced NSCLC with metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cátions/administração & dosagem , Lipossomos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/administração & dosagem , Células A549 , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual
11.
Pharm Res ; 36(11): 161, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529284

RESUMO

PURPOSE: Apolipoprotein E2 (ApoE2) gene therapy is a potential disease-modifying therapy for Alzheimer's disease (AD). We investigated the potential of plasmid encoding ApoE2 loaded brain-targeted functionalized-liposomes for treatment of AD. This was achieved via systemic administration of liposomes entrapping therapeutic gene targeting the brain of mice. METHODS: Targeting and transfection efficiency of designed liposomes were determined in bEnd.3, primary glial and primary neuronal cells. The ability of liposomal formulations to translocate across in vitro blood-brain barrier (BBB) and, thereafter, transfect primary neuronal cells was investigated using in vitro triple co-culture BBB model. We quantified ApoE expression in the brain of mice after single intravenous injection of brain-targeted liposomes loaded with plasmid ApoE2. RESULTS: Dual surface modification enhanced the in vitro transfection efficiency of designed liposomes. Successful delivery of therapeutic gene overcoming BBB by Transferrin-Penetratin- modified liposomes was demonstrated both in vitro and in vivo. Significant (p < 0.05) increase in ApoE levels in the brain of mice was observed after intravenous administration of Tf-Pen-liposomes encasing plasmid ApoE2. CONCLUSION: The results indicate that dual-ligand based liposomal gene delivery systems had both enhanced brain targeting and gene delivery efficiencies. Transferrin-Penetratin modified liposomes for delivery of plasmid ApoE2 has great potential for AD treatment.


Assuntos
Apolipoproteína E2/genética , Barreira Hematoencefálica/metabolismo , Terapia Genética , Lipossomos/química , Nanopartículas/química , Doença de Alzheimer/terapia , Animais , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Feminino , Humanos , Lipossomos/administração & dosagem , Lipossomos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Transferrina/química , Transferrina/metabolismo
12.
Pharm Res ; 36(11): 162, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529336

RESUMO

PURPOSE: Mucins are the principal glycoproteins in mucus and have been implicated in the limitation of intestinal drug absorption; however, the contribution of these molecules to intestinal drug absorption remains unclear. In this study, the relationship between the effect of the mucus layer on intestinal drug permeation and mucin distribution in different parts of the rat gastrointestinal tract was evaluated. METHODS: The intestinal permeability of various lipophilic drugs in rat small intestine was evaluated using the in vitro sac method. The expression profiles of mucin mRNA and proteins were evaluated by quantitative real-time RT-PCR and western blotting, respectively. RESULTS: The intestinal permeability of griseofulvin and antipyrine was enhanced by dithiothreitol (DTT) treatment in the proximal small intestine, such as duodenum and jejunum, but not in the distal regions. The mRNA expression analysis of rat mucin genes revealed that the intestinal expression of Muc5ac was considerably higher in the duodenum, whereas that of Muc1, Muc2, and Muc3A was gradually increased toward the lower intestine. In addition, Muc5ac protein was detected only in the luminal fluids from the proximal small intestine after DTT treatment. CONCLUSIONS: Mucus limits the intestinal permeation of lipophilic drugs in the rat proximal small intestine, in which Muc5ac may be involved.


Assuntos
Antipirina/farmacologia , Griseofulvina/farmacologia , Intestino Delgado/metabolismo , Lipossomos , Glicoproteínas de Membrana/metabolismo , Mucinas/metabolismo , Animais , Antipirina/metabolismo , Composição de Medicamentos , Griseofulvina/metabolismo , Absorção Intestinal , Mucinas/genética , Ratos
13.
Int J Nanomedicine ; 14: 6249-6268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496684

RESUMO

Purpose: To develop an intravesical instillation system for the treatment of bladder cancer, rapamycin (Rap) was encapsulated into liposomes and then homogeneously dispersed throughout a poloxamer 407 (P407)-based hydrogel. Methods: Rap-loaded conventional liposomes (R-CL) and folate-modified liposomes (R-FL) were prepared using a film hydration method and pre-loading technique, and characterized by particle size, drug entrapment efficiency, and drug loading. The cellular uptake behavior in folate receptor-expressing bladder cancer cells was observed by flow cytometry and confocal laser scanning microscopy using a fluorescent probe. In vitro cytotoxic effects were evaluated using MTT assay, colony forming assay, and Western blot. For in vivo intravesical instillation, Rap-loaded liposomes were dispersed in P407-gel, generating R-CL/P407 and R-FL/P407. Gel-forming capacities and drug release were evaluated. Using the MBT2/Luc orthotopic bladder cancer mouse model, in vivo antitumor efficacy was evaluated according to regions of interest (ROI) measurement. Results: R-CL and R-FL were successfully prepared, at approximately <160 nm, 42% entrapment efficiency, and 57 µg/mg drug loading. FL cellular uptake was enhanced over 2-fold than that of CL; folate receptor-mediated endocytosis was confirmed using a competitive assay with folic acid pretreatment. In vitro cytotoxic effects increased dose-dependently. Rap-loaded liposomes inhibited mTOR signaling and induced autophagy in urothelial carcinoma cells. With gelation time of <30 seconds and gel duration of >12 hrs, both R-CL/P407 and R-FL/P407 preparations transformed into gel immediately after instillation into the mouse bladder. Drug release from the liposomal gel was erosion controlled. In orthotopic bladder cancer mouse model, statistically significant differences in ROI values were found between R-CL/P407 and R-FL/P407 groups at day 11 (P=0.0273) and day 14 (P=0.0088), indicating the highest tumor growth inhibition by R-FL/P407. Conclusion: Intravesical instillation of R-FL/P407 might represent a good candidate for bladder cancer treatment, owing to its enhanced retention and FR-targeting.


Assuntos
Ácido Fólico/química , Hidrogéis/química , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Temperatura Ambiente , Administração Intravesical , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Coloides , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Receptores de Folato com Âncoras de GPI/metabolismo , Humanos , Lipossomos , Camundongos , Tamanho da Partícula , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico
14.
Zhonghua Fu Chan Ke Za Zhi ; 54(9): 588-594, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31550774

RESUMO

Objective: To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. Methods: This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. Results: (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all P>0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, P=0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (P=0.968, P=0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (P=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, P<0.05), as well as the incidence of alopecia (67.9% vs 79.2%, P<0.05) and myalgia (17.9% vs 28.9%, P<0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (P>0.05). Conclusion: In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Paclitaxel/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Lipossomos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
15.
Eur J Pharm Biopharm ; 144: 154-164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542438

RESUMO

Curcumin, a multi-targeting pharmacologically active compound, is a promising molecule for the treatment of skin inflammation and infection in chronic wounds. However, its hydrophobic nature remains to be a challenge in development of its pharmaceutical products, including dermatopharmaceuticals. Here we propose deformable liposomes (DLs) as a mean to overcome the curcumin limitations in skin treatment. We explored the properties and biological effects of curcumin containing DLs (curcumin-DLs) with varying surface charge by preparing the neutral (NDLs), cationic (CDLs) and anionic (ADLs) nanocarriers. The vesicles of mean diameter 200-300 nm incorporated high curcumin load mirroring the type of employed surfactant. Curcumin-CDLs provided the most sustained ex vivo penetration of curcumin through the full thickness human skin. Although the curcumin-CDLs were the most potent regarding the in vitro anti-inflammatory activity, all curcumin-DLs were superior to curcumin in solution (control). No cytotoxicity in human skin fibroblasts was detected. All DLs significantly inhibited bacterial Staphylococcus aureus and Streptococcus pyogenes growth in vitro. The curcumin-CDLs were found superior to other DLs. The incorporation of curcumin in DLs enabled both its sustained skin penetration and enhancement of its biological properties. Cationic nanocarriers enhanced the activities of curcumin to the greatest extent.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Lipossomos/química , Pele/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Administração Cutânea , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Fibroblastos/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Tamanho da Partícula , Pele/microbiologia , Absorção Cutânea/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Tensoativos/química
16.
Int J Nanomedicine ; 14: 5911-5924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534330

RESUMO

Purpose: Magnetoliposomes (MLs) have shown great potential as magnetic resonance imaging contrast agents and as delivery vehicles for cancer therapy. Targeting the MLs towards the tumor cells or neovascularization could ensure delivery of drugs at the tumor site. In this study, we evaluated the potential of MLs targeting the αvß3 integrin overexpressed on tumor neovascularization and different tumor cell types, including glioma and ovarian cancer. Methods: MLs functionalized with a Texas Red fluorophore (anionic MLs), and with the fluorophore and the cyclic Arginine-Glycine-Aspartate (cRGD; cRGD-MLs) targeting the αvß3 integrin, were produced in-house. Swiss nude mice were subcutaneously injected with 107 human ovarian cancer SKOV-3 cells. Tumors were allowed to grow for 3 weeks before injection of anionic or cRGD-MLs. Biodistribution of MLs was followed up with a 7T preclinical magnetic resonance imaging (MRI) scanner and fluorescence imaging (FLI) right after injection, 2h, 4h, 24h and 48h post injection. Ex vivo intratumoral ML uptake was confirmed using FLI, electron paramagnetic resonance spectroscopy (EPR) and histology at different time points post injection. Results: In vivo, we visualized a higher uptake of cRGD-MLs in SKOV-3 xenografts compared to control, anionic MLs with both MRI and FLI. Highest ML uptake was seen after 4h using MRI, but only after 24h using FLI indicating the lower sensitivity of this technique. Furthermore, ex vivo EPR and FLI confirmed the highest tumoral ML uptake at 4 h. Last, a Perl's stain supported the presence of our iron-based particles in SKOV-3 xenografts. Conclusion: Uptake of cRGD-MLs can be visualized using both MRI and FLI, even though the latter was less sensitive due to lower depth penetration. Furthermore, our results indicate that cRGD-MLs can be used to target SKOV-3 xenograft in Swiss nude mice. Therefore, the further development of this particles into theranostics would be of interest.


Assuntos
Fenômenos Magnéticos , Neoplasias/irrigação sanguínea , Neovascularização Patológica/terapia , Oligopeptídeos/química , Animais , Linhagem Celular Tumoral , Difusão Dinâmica da Luz , Feminino , Humanos , Integrina alfaVbeta3/metabolismo , Lipossomos , Imagem por Ressonância Magnética , Camundongos Nus , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neovascularização Patológica/patologia , Imagem Óptica , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Adv Exp Med Biol ; 1159: 33-48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31502198

RESUMO

Are ceramide molecules capable of self-assembling in biological and phospholipid membranes to form ceramide channels: membrane channels capable to translocating proteins through said membranes? A number of papers have been published which support the conclusion that ceramide forms these large channels in membranes. The evidence is extensive and consisting of: flux studies using isolated mitochondria, liposomes and planar membranes; visualization by electron microscopy; elastic deformation studies; and regulation by Bcl-2 family proteins. The evidence supports a structural model of the channel shown to be stable by molecular dynamic simulations and having structural and mechanical properties consistent with multiple experiments. Yet the novelty of this claim raises legitimate questions. Indeed, a recent report questions the existence of ceramide channels based on liposome experiments. This review presents both a comprehensive description of the major observations supporting the case that ceramide channels do exist and addresses the issues raised in the skeptical report.


Assuntos
Membrana Celular/química , Ceramidas/química , Lipossomos/química , Mitocôndrias/química , Fosfolipídeos , Proteínas Proto-Oncogênicas c-bcl-2
18.
Eur J Pharm Biopharm ; 144: 18-39, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446046

RESUMO

Development of nanocarriers for drug delivery has received considerable attention due to their potential in achieving targeted delivery to the diseased site while sparing the surrounding healthy tissue. Safe and efficient drug delivery has always been a challenge in medicine. During the last decade, a large amount of interest has been drawn on the fabrication of surfactant-based vesicles to improve drug delivery. Niosomes are self-assembled vesicular nano-carriers formed by hydration of non-ionic surfactant, cholesterol or other amphiphilic molecules that serve as a versatile drug delivery system with a variety of applications ranging from dermal delivery to brain-targeted delivery. A large number of research articles have been published reporting their fabrication methods and applications in pharmaceutical and cosmetic fields. Niosomes have the same advantages as liposomes, such as the ability to incorporate both hydrophilic and lipophilic compounds. Besides, niosomes can be fabricated with simple methods, require less production cost and are stable over an extended period, thus overcoming the major drawbacks of liposomes. This review provides a comprehensive summary of niosomal research to date, it provides a detailed overview of the formulation components, types of niosomes, effects of components on the formation of niosomes, fabrication and purification methods, physical characterization techniques of niosomes, recent applications in pharmaceutical field such as in oral, ocular, topical, pulmonary, parental and transmucosal drug delivery, and cosmetic applications. Finally, limitations and the future outlook for this delivery system have also been discussed.


Assuntos
Cosméticos/química , Lipossomos/química , Surfactantes Pulmonares/química , Tensoativos/química , Administração Cutânea , Animais , Química Farmacêutica/métodos , Colesterol/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos
19.
Eur J Pharm Biopharm ; 142: 518-530, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365879

RESUMO

Despite substantial advancements in divergent drug delivery systems (DDS), there is still room for novel and innovative nanoparticle-mediated drug delivery methodologies such as core/shell liposomes to deliver drugs in a kinetically controlled manner into the active site without any side effects. Herein, ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl) bis (2-methoxy-4,1-phenylene) diacetate acetyl curcumin (AC)-loaded poly(lactic-co-glycolic acid) (PLGA) core/shell liposome nanoparticles (ACPCSLNPs) were prepared using an electron spray method under an applied electric field, which facilitated the uniform formation of nano-sized liposome nanoparticles (LNPs). Then, kinetically controlled and sustained drug release profiles were investigated using the as-prepared ACPCSLNPs. Moreover, the inner polymeric core could not only induce the generation of electrostatic interactions between the polymer and drug molecules but could also affect the prominent repulsions between the polar head groups of lipids and the nonpolar drug molecules. As a result, the sustained maximum release of the drug molecules (~48.5%) into the system was observed over a long period (~4 days). Furthermore, cell cytotoxicity studies were conducted in a human cervical cancer cell line (HeLa) and a healthy human dermal fibroblast cell line (HDFa) by employing all AC loaded LNPs along with free drugs. Multicolor cell imaging was also observed in HeLa cells using ACPCSLNPs. Notably, more curcumin was released from the ACPCSLNPs than AC due to the presence of polar group attractions and polar-polar interactions between the lipid head groups and curcumin since curcumin is more soluble than AC in aqueous medium. In addition, the predictions of the release kinetic patterns were also investigated thoroughly using the exponential-based Korsmeyer-Peppas (K-P) and Higuchi models for drug-loaded LNPs and PLGA NPs, respectively.


Assuntos
Curcumina/química , Lipossomos/química , Nanopartículas/química , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Células HeLa , Humanos , Lipídeos/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanomedicina Teranóstica/métodos
20.
Chem Commun (Camb) ; 55(73): 10940-10943, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441920

RESUMO

Different from traditional "always on" photothermal therapy (PTT) agents, tumor microenvironment responsive agents showed more tumor specificity and lower photo-toxicity to normal tissues. Herein, a photo-stable and reversible pH responsive phenazine dye (PIOH) was synthesized and assembled with liposomes forming nanoparticles (PIOH-NPs), which exhibited a strong NIR absorption in a weak acid environment and were successfully utilized for photoacoustic (PA) imaging-guided photothermal therapy in mice.


Assuntos
Antineoplásicos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Fenazinas/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Colesterol/química , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Concentração de Íons de Hidrogênio , Hipertermia Induzida/métodos , Lecitinas/química , Lipossomos/química , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Fenazinas/síntese química , Fenazinas/química , Fenazinas/toxicidade , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Microambiente Tumoral/fisiologia
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