scholarly journals Lomustine Incorporated Lipid Nanostructures Demonstrated Preferential Anticancer Properties in C6 Glioma Cell Lines with Enhanced Pharmacokinetic Profile in Mice

2021 ◽  
Vol 68 (4) ◽  
pp. 970-982
Author(s):  
Bhabani Sankar Satapathy ◽  
Ladi Alik Kumar ◽  
Gurudutta Pattnaik ◽  
Binapani Barik

Effective treatment of glioma still stands as a challenge in medical science. The work aims for the fabrication and evaluation of lipid based nanostructures for improved delivery of lomustine to brain tumor cells. Experimental formulations (LNLs) were developed by modified lipid layer hydration technique and evaluated for different in vitro characteristics like particle size analysis, surface charge, surface morphology, internal structure, in vitro drug loading, drug release profile etc. Anticancer potential of selected LNLs was tested in vitro on C6 glioma cell line. Electron microscopic study depicted a size of less than 50 nm for the selected LNLs along wirh 8.8% drug loading with a sustained drug release tendency over 48 h study period. Confocal microscopy revealed resonable internalization of the selected LNL in C6 cells. LNLs were found more cytotoxic than free drug and blank nanocarriers as depicted from MTT assay. The selected LNL showed improved pharmacokinetic profile both in blood and brain in the experimental mice models along with negligible hemolysis in mice blood cells. Further studies are warranted for the future translation of LNLs at clinics.

Biomaterials ◽  
2010 ◽  
Vol 31 (24) ◽  
pp. 6201-6206 ◽  
Author(s):  
Ping Wang ◽  
Lei Li ◽  
Cheng Zhang ◽  
Qunfang Lei ◽  
Wenjun Fang

2012 ◽  
Vol 62 (4) ◽  
pp. 529-545 ◽  
Author(s):  
Anuj Chawla ◽  
Pooja Sharma ◽  
Pravin Pawar

The aim of the study was to prepare site specific drug delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified emulsification method followed by cross-linking with CaCl2, which was further coated with the pH dependent polymer Eudragit S-100 (2.5 or 5 %) to prevent drug release in the upper gastrointestinal environment. Microspheres were characterized by FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and evaluated by scanning electron microscopy, particle size analysis, drug loading efficiency, in vitro mucoadhesive time study and in vitro drug release study in different simulated gastric fluids. Stability studies of the optimized formulation were carried out for 6 months. SEM images revealed that the surface morphology was rough and smooth for core and coated microspheres, respectively. Core microspheres showed better mucoadhesion compared to coated microspheres when applied to the mucosal surface of freshly excised goat colon. The optimized batch of core microspheres and coated microspheres exhibited 98.42 ± 0.96 and 95.58 ± 0.74 % drug release, respectively. Drug release from all sodium alginate microsphere formulations followed Higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the Korsmeyer-Peppas equation with a Fickian kinetics mechanism. Stability study suggested that the degradation rate constant of microspheres was minimal, indicating 2 years shelf life of the formulation.


2019 ◽  
Vol 11 (11) ◽  
pp. 1522-1530
Author(s):  
Mahwish Kamran ◽  
Mir Azam Khan ◽  
Muhammad Shafique ◽  
Maqsood ur Rehman ◽  
Waqar Ahmed ◽  
...  

Atorvastatin is an extensively used lipid lowering agent. But the vital issue associated with it is low oral bioavailability (12%) owing to poor aqueous solubility. To overcome this tribulation, binary solid lipid nano suspension of Atorvastatin (ATO) was formulated by solvent diffusion method. The combination of stearic acid and oleic acid was utilized as a lipid carrier with Tween-80 (surfactant) along with Polyvinylpyrrolidone (co-surfactant). Optimized nano formulation was prepared by changing the formulation variables. Optimized nano suspension (ATO-4) represented particle size 228.3 ± 2.1 nm and polydispersity index (PDI) 0.225 ± 0.02 with zeta potential (ZP) – 33.6 ± 0.02 mV. Encapsulation efficiency along with drug loading capacity was 88.3 ± 2.5% and 4.9 ± 0.14% respectively. Scanning electron microscopic (SEM) analysis exposed spherical shaped amorphous particles. Differential scanning calorimetry (DSC) as well as X-ray powder diffraction (P-XRD) established reduction in drug's crystalline state. Fourier transform infrared (FTIR) spectroscopy exposed no interaction amongst the drug and formulation contents. In-vitro studies revealed sustained pattern of drug release. Stability studies confirmed refrigerated temperature as most suitable for storage of binary solid lipid nano suspension. Plasma concentration versus time curve ascertained 2.78-fold increase in oral bioavailability of ATO nano suspension compared to the marketed product (Lipitor®). Findings proposed desired improvement in oral bioavailability of ATO nano suspension with sustained drug release profile. Thus, binary solid lipid nano suspension could be utilized as an advanced drug delivery system for oral deliverance of hydrophobic drugs.


1990 ◽  
Vol 72 (5) ◽  
pp. 782-785 ◽  
Author(s):  
Justin D. Cohen ◽  
H. Ian Robins ◽  
Manucher J. Javid

✓ The cytotoxic, antiproliferative, and radiosensitizing effects of thymidine (a nucleoside metabolite) were studied using the C6 glioma cell line in vitro. Radiosensitization by a combination of thymidine and 41.8°C hyperthermia was also evaluated. Thymidine concentrations above 100 µg/ml completely inhibited C6 proliferation while concentrations of 100 to 1000 µg/ml (for up to 24 hours) decreased C6 cell survival to as little as 7.4% compared to untreated control cells. Radiosensitivity was enhanced by the administration of thymidine alone (400 µg/ml × 24 hours before irradiation); sensitization by 41.8°C hyperthermia alone (1 hour ending immediately before irradiation) was less pronounced. Thymidine and hyperthermia together produced greater radiosensitization than did heat alone or thymidine alone. These data support the further investigation of thymidine as a neuro-oncology radiosensitizer.


Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 2155-2162 ◽  
Author(s):  
Bryan L. Spangelo ◽  
Derald D. Farrimond ◽  
Mahesh Thapa ◽  
Charles M. Bulathsinghala ◽  
Kay-Lynn Bowman ◽  
...  

RSC Advances ◽  
2016 ◽  
Vol 6 (55) ◽  
pp. 50336-50348 ◽  
Author(s):  
Mahalingam Rajamanickam Vijayakumar ◽  
Lakshmi Kumari ◽  
Krishna Kumar Patel ◽  
Parameswara Rao Vuddanda ◽  
Kiran Yellappa Vajanthri ◽  
...  

trans-Resveratrol (RSV), a natural molecule isolated from red wine, is widely known for several therapeutic potentials.


2018 ◽  
Vol 5 (1) ◽  
pp. 99-108
Author(s):  
L.H. Ching ◽  
S. Mahmood ◽  
R. Edros ◽  
R.V. Kutty

Theranostic micelles and polymeric nanocarrier-based drug delivery system are well known techniques that involve a diagnostic agent in polymeric micelles for a combination of therapy by using a co-delivery approach which can help in detection of a cancer cell in an early stage, increase killing effect and suppress multi-drug resistance (MDS) for better therapeutic effectiveness. The aim of this study is to develop a dual modality micellar system using D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a nanocarrier for co-delivery of docetaxel as a model chemotherapeutic drug and coumarin-6 as a model fluorescence imaging agent for simultaneous cancer imaging and therapy in an early stage. The theranostic micelles were prepared by a solvent casting method and characterized by their particle size, drug loading, drug encapsulation efficiency (EE) and in-vitro drug release profile. These dual modality micellar system TPDC6 micelles were successfully developed with average particle size of 79.59±0.57 nm in diameter and drug loading up to 15.46±1.02 % (EE of 78.99±1.26%) and 9.83±0.76 % (EE of 36.20±0.89%) for docetaxel and coumarin-6 respectively. Besides, the in-vitro drug release profile of the micelles revealed a desired sustained and controlled drug release manner for both docetaxel (21.62±0.36%) and coumarin-6 (10.70±0.46%). In conclusion, the micelles size obtained is in the favourable range for passive targeting through enhanced permeability and retention (EPR) effect and the drug loading and encapsulation efficiency attained are adequate for therapy and diagnosis purposes on cancer cells. This dual modality system is taking great advantages for tumour imaging and inhibition of tumour growth which is very important for early cancer detection.


1998 ◽  
Vol 1 (1) ◽  
pp. 20-23
Author(s):  
Adlija Jevrić-Čaušević

In vitro antiproliferative effects of SarCNU and GMI ganglioside were tested in different concentration ratios in C6 glioma cell culture. Based on MTT assay and a protein assay, cytotoxicity of each agent separately and the two agents combined was tested. When the cells were treated with different concentrations of ganglioside ranging from 10-’ to 10-2, the number of viable cells decreased highly on days two and seven, regardless of the concentration of the agent applied. SarCNU, as expected, has caused antiproliferative effects which highly correlated with the concentration of the agent tested. When the C6 glioma cell culture was treated with the two agents combined in the optimal concentration causing the above mentioned cytotoxicity, effects observed did not correlate with those observed for each agent alone, suggesting in this case the expression of highly neuroprotective effects of ganglioside GMI.


Author(s):  
UMESH KUMAR SHARMA

Objective: In the present research, the main objective was to investigate the possibility of designing, fabricating, and optimizing a disposable ocular film-based drug delivery system. Methods: Moxifloxacin hydrochloride was loaded onto the prepared disposable ocular films by the soaking method. Results: The drug loading conditions were studied, and it was found that the maximum drug loading was achieved in 3 hours at pH 6.5 of the drug solution. It was also observed that the drug loading efficacy and in vitro drug release profile can be monitored by varying the ocular film composition. The ocular films were then characterized for thickness uniformity, size uniformity, weight uniformity, swelling index, surface pH, breaking on elongation, folding endurance, bio-adhesive strength, transparency, drug loading efficiency, moisture content, morphological characteristics, and in vitro drug release profiles. Conclusion: Based on the results, it was concluded that the developed disposable ocular films demonstrate a significant prolonged drug release within the therapeutic range of up to 12 h, which is promising as a novel disposable contact lens-based ocular drug delivery system.


Author(s):  
Niket N Garude ◽  
Rachel B Geevarghese

Nanostructure Lipid Carrier (NLC) is one of the lipid-based drug delivery systems that are used as carrier for delivery of drugs. NLC are composed of mixture of solid lipid and liquid lipid, which form imperfect type of lipid matrix with improved drug loading capacity, drug release profile and stability. The aim of the present study was to develop and characterize nanostructure lipid carrier for transdermal delivery of pioglitazone (PZ) to overcome the problems related with oral route of administration and to improve systemic availability. NLC’s were prepared by high-speed homogenization method. Optimized NLC formulation was evaluated for particle size, percentage entrapment efficiency, surface morphology, DSC analysis, in-vitro drug release etc. The optimized NLC formulation was formulated as a transdermal patch and evaluated for in vitro drug release study and primary skin irritation study. In vivo hypoglycaemic activity of pioglitazone -NLC loaded transdermal patch was studied in comparison with its orally administered suspension. PZ- NLC loaded transdermal patch was found to be non-irritant and showed reduction in blood glucose level in a controlled manner up to 24 hrs.    


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