Development of a dry powder for inhalation of nanoparticles codelivering cisplatin and ABCC3 siRNA in lung cancer

2021 ◽  
Author(s):  
Vivek Patel ◽  
Denish Bardoliwala ◽  
Rohan Lalani ◽  
Sushilkumar Patil ◽  
Saikat Ghosh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Polymer Concentration ◽  
Pulmonary Delivery ◽  
Multidrug Resistant ◽  
Molar Ratio ◽  
Design System ◽  
Pharmacokinetic Parameters ◽  
Lipid Concentration ◽  
Dry Powder

Background: The current study sought to formulate a dry powder inhalant (DPI) for pulmonary delivery of lipopolymeric nanoparticles (LPNs) consisting of cisplatin and siRNA for multidrug-resistant lung cancer. siRNA against ABCC3 gene was used to silence drug efflux promoter. Results & discussion: The formulation was optimized through the quality by design system by nanoparticle size and cisplatin entrapment. The lipid concentration, polymer concentration and lipid molar ratio were selected as variables. The DPI was characterized by in vitro deposition study using the Anderson cascade impactor. DPI formulation showed improved pulmonary pharmacokinetic parameters of cisplatin with higher residence time in lungs. Conclusion: Local delivery of siRNA and cisplatin to the lung tissue resulted into an enhanced therapeutic effectiveness in combating drug resistance.

scholarly journals NANO-VESICLES OF SALBUTAMOL SULPHATE IN METERED DOSE INHALERS: FORMULATION, CHARACTERIZATION AND IN VITRO EVALUATION

2017 ◽  
Vol 9 (6) ◽  
pp. 100 ◽  
Author(s):  
Mona G. Arafa ◽  
Bassam M. Ayoub
Keyword(s):  
In Vitro Release ◽  
Pulmonary Delivery ◽  
Entrapment Efficiency ◽  
Reversed Phase ◽  
Molar Ratio ◽  
Metered Dose Inhalers ◽  
Salbutamol Sulphate ◽  
Novel Approach ◽  
Metered Dose

Objective: The present work was aimed to prepare niosomes entrapping salbutamol sulphate (SS) using reversed phase evaporation method (REV).Methods: Niosomes were prepared by mixing span 60 and cholesterol in 1:1 molar ratio in chloroform, SS in water was then added to organic phase to form niosomal SS. Formulations after evaporation of chloroform, freeze centrifuged then lyophilized, were evaluated for particles size, polydispersity index (Pdi), zeta-potential, morphology, entrapment efficiency (EE%) and in vitro release. For pulmonary delivery; metered dose inhalers (MDI) were prepared by suspending SS niosomes equivalent to 20 mg SS in hydrofluoroalkane (HFA). The metered valve was investigated for leakage rate, the total number of puffs/canister, weight/puff, dose uniformity and particle size.Results: The results showed spherical niosomes with 400-451 nm particles that entrapped 66.19% of SS. 76.54±0.132% SS release from niosomes that showed a controlled release profile for 8h. The leakage test was not exceeding 4 mg/3 d, the number of puffs were up to 200puffs/canister, the dose delivered/puff was 0.1 mg and 0.64-4.51μm niosomal aerosol.Conclusion: The results indicate an encouraging strategy to formulate a controlled drug delivery by entrapping (SS) in niosomes which could be packaged into (MDI) that met the requirements of (USP) aerosols guidelines which offering a novel approach to respiratory delivery.

scholarly journals Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 884
Author(s):  
Zhen Zhang ◽  
Chaoliang He ◽  
Xuesi Chen
Keyword(s):  
Antitumor Effect ◽  
Click Reaction ◽  
Polymer Concentration ◽  
Mechanical Analysis ◽  
Molar Ratio ◽  
Phase Cell ◽  
Mice Model ◽  
Mcf 7

Injectable, covalently cross-linked hydrogels have been widely investigated in drug delivery systems due to their superior mechanical properties and long-term stability. Conventional covalently cross-linked hydrogels are formed by chemical reactions that may interfere with natural biochemical processes. In this work, we developed an injectable polypeptide hydrogel via an inverse electron demand Diels-Alder reaction between norbornene modified poly(L-glutamic acid) (PLG-Norb) and tetrazine functionalized four-arm poly(ethylene glycol) (4aPEG-T) for localized release of cisplatin (CDDP). The rapid and bioorthogonal click reaction allowed for hydrogel formation within a few minutes after mixing the two polymer solutions in phosphate buffer saline (PBS). Dynamic mechanical analysis suggested that the storage modulus of the hydrogel could be readily tuned by changing the polymer concentration and the molar ratio of the two functional groups. The carboxyl groups of PLG-Norb were used to form polymer–metal complexation with CDDP, and the controlled release of the antitumor drug was achieved in PBS. The CDDP-loaded hydrogel displayed an antitumor effect against MCF-7 cells in vitro, through S phase cell cycle arrest. After subcutaneous injection in rats, the hydrogel was rapidly formed in situ and showed good stability in vivo. In an MCF-7-bearing nude mice model, the CDDP-loaded hydrogel exhibited an improved antitumor effect with reduced systemic toxicity. Overall, the injectable click polypeptide hydrogel shows considerable potential as a platform for localized and sustained delivery of antitumor drugs.

scholarly journals Cisplatin and Vinorelbine -Mediated Electrochemotherapeutic Approach Against Multidrug Resistant Small Cell Lung Cancer (H69AR) In Vitro

2019 ◽  
Vol 39 (7) ◽  
pp. 3711-3718 ◽  
Author(s):  
MAŁGORZATA DRĄG-ZALESIŃSKA ◽  
JOLANTA SACZKO ◽  
ANNA CHOROMAŃSKA ◽  
ANNA SZEWCZYK ◽  
NINA REMBIAŁKOWSKA ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Multidrug Resistant ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 294 ◽  
Author(s):  
Chishti ◽  
Dhamecha ◽  
Jalalpure ◽  
Dehghan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pulmonary Delivery ◽  
Small Cell ◽  
Small Cell Lung ◽  
Dry Powder ◽  
Term Delivery

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around −36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).

scholarly journals Inhaled ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) nanoparticles from dry powder inhaler formulation for the potential treatment of lower respiratory tract infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261720
Author(s):  
Mohammad Zaidur Rahman Sabuj ◽  
Tim R. Dargaville ◽  
Lisa Nissen ◽  
Nazrul Islam
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Drug Loading ◽  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Lower Respiratory Tract Infections ◽  
Dry Powder ◽  
Tract Infections

Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses with frequent administration and cause dose-related adverse effects. To overcome this problem, we investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs. NPs were prepared using a straightforward co-assembly reaction carried out by the intermolecular hydrogen bonding among PEtOx, tannic acid (TA), and CIP. The prepared NPs were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The CIP was determined by validated HPLC and UV spectrophotometry methods. The CIP loading into the PEtOx was between 21–67% and increased loading was observed with the increasing concentration of CIP. The NP sizes of PEtOx with or without drug loading were between 196–350 nm and increased with increasing drug loading. The in vitro CIP release showed the maximum cumulative release of about 78% in 168 h with a burst release of 50% in the first 12 h. The kinetics of CIP release from NPs followed non-Fickian or anomalous transport thus suggesting the drug release was regulated by both diffusion and polymer degradation. The in vitro aerosolization study carried out using a Twin Stage Impinger (TSI) at 60 L/min air flow showed the fine particle fraction (FPF) between 34.4% and 40.8%. The FPF was increased with increased drug loading. The outcome of this study revealed the potential of the polymer PEtOx as a carrier for developing CIP-loaded PEtOx NPs as DPI formulation for pulmonary delivery against LRTIs.

scholarly journals Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249683
Author(s):  
Md Abdur Rashid ◽  
Saiqa Muneer ◽  
Tony Wang ◽  
Yahya Alhamhoom ◽  
Llew Rintoul ◽  
...  
Keyword(s):  
Low Dose ◽  
Structural Integrity ◽  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Magnesium Stearate ◽  
Hplc Method ◽  
Dry Powder ◽  
Scanning Calorimetry ◽  
X Ray

This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.

scholarly journals Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Ashley N. Brown ◽  
George L. Drusano ◽  
Jonathan R. Adams ◽  
Jaime L. Rodriquez ◽  
Kalyani Jambunathan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Optimal Dosage ◽  
Dependent Manner ◽  
Once Daily ◽  
Content Type ◽  
Toxicity Relationship

ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. IMPORTANCE The emergence and spread of multidrug-resistant M. tuberculosis are a major threat to global public health. Linezolid is an oxazolidinone that is licensed for human use and has demonstrated potent activity against multidrug-resistant M. tuberculosis. However, long-term use of linezolid has shown to be toxic in patients, often resulting in thrombocytopenia. We examined therapeutic linezolid regimens in an in vitro model to characterize the exposure-toxicity relationship. The antibacterial activity against M. tuberculosis was also assessed for these regimens, including the amplification or suppression of resistant mutant subpopulations by the chosen regimen. Higher exposures of linezolid resulted in greater antibacterial activity, but with more toxicity and, for some regimens, increased resistant mutant subpopulation amplification, illustrating the trade-off between activity and toxicity. These findings can provide valuable insight for designing optimal dosage regimens for linezolid that are part of the long combination courses used to treat multidrug-resistant M. tuberculosis.

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