Hyaluronic Acid Modified Risedronate and Teriparatide Co-loaded Nanocarriers for Improved Osteogenic Differentiation of Osteoblasts for the Treatment of Osteoporosis

2019 ◽  
Vol 25 (27) ◽  
pp. 2975-2988 ◽  
Author(s):  
Mohammed A.S. Abourehab

Background: Owing to its multifactorial intricate pathogenesis, combined therapeutic regimen is considered appropriate for the treatment of osteoporosis. However, a multi-drug regimen is also associated with adverse effects due to the non-specific distribution of drugs. Therefore, the present study aims for efficient codelivery of risedronate (RDN) (a potent bone anti-resorptive drug) and teriparatide (TPD) (anabolic agent) as hyaluronic acid (HA)-modified chitosan nanoparticles (NPs). Methods: RDN/TPD NPs were synthesized using the high- pressure homogenization – solvent evaporation technique. The fabricated NPs were then characterized and optimized for suitable physicochemical characteristics. The optimized NPs were then evaluated for bone remodeling potential via assessment of time-mannered modulation in proliferation, differentiation, and mineralization of osteoblasts. Results: Results showed that HA-RDN/TPD NPs exhibited excellent physicochemical characteristics (nanoscopic size, stable zeta potential, high entrapment efficiency, and smooth spherical shape) and remained stable upon storage in the refrigerator. Assessment of various aspects of the cell growth cycle (i.e., proliferation, differentiation, and mineralization) evidenced promising bone regeneration efficacy of HA-RDN/TPD NPs. Conclusion: This new strategy of employing simultaneous delivery of anti-resorptive and bone-forming agents would open new horizons for scientists, researchers, and healthcare providers as an efficient pharmacotherapy for the treatment of osteoporosis.

2013 ◽  
Vol 662 ◽  
pp. 149-152
Author(s):  
Yan Hao ◽  
Hao Wu ◽  
Wei Li ◽  
Xiao Mei Luo ◽  
Kai Zhao

In this study, the researcher’s interest is focused on establishing a model with La Sota live vaccine immobilized into chitosan, which was prepared using a ionic gelation method. The formulation, preparation procedure, influence factors, physicochemical characteristics were evaluated. The results of study demonstrate that the NDV-CS-NPs have been produced with suitable size, morphous regulation, extremely spherical shape, regular and well-distributed. The NDV-CS-NPs produced by the optimal formulation were average size (371.1nm) and proper zata potential (+2.84 mV). The entrapment efficiency was (74±3.7) %. It can provide a new useful information for the development and evaluation of synthetic vaccines.


2017 ◽  
Vol 6 (3) ◽  
pp. 16-22 ◽  
Author(s):  
Satish K. Mandlik ◽  
Nisharani S. Ranpise

The present study investigated the implementation of 32 factorial design of experiment and statistical analysis for the optimization of chitosan nanoparticles containing zolmitriptan an antimigraine drug. The influence of chitosan concentration (X1) and sodium tripoly phosphate (X2) on responses namely nanoparticle size (Y1), and entrapment efficiency (Y2), was studied. As per design, nine runs of nanoparticles were prepared by modified ionic gelation method using high speed vortex mixing. The particle size was found in the range of 151-880 nm and entrapment efficiency was 72.3-81.2%. A statistical analysis was performed using licensed design expert software V.8.0 with respect to ANOVA, regression analysis. The contour plots and response surface plots showed visual representation of relationship between the experimental responses and the set of independent variables. Regression model equations were validated by a numerical and graphical optimization method. Further, optimized drug loaded nanoparticles showed +23.7mV zeta potential indicating storage stability, electron micrograph reflects spherical shape and mixed type of drug release followed by Fickian diffusion (n=0.266) was observed. Thus, using systematic factorial design approach, desirable goals can be achieved in shortest possible time with lesser number of experiments which was proven to be an effective tool in quality by design.Mandlik and Ranpise, International Current Pharmaceutical Journal, February 2017, 6(3): 16-22http://www.icpjonline.com/documents/Vol6Issue3/01.pdf


2011 ◽  
Vol 194-196 ◽  
pp. 541-544
Author(s):  
Orapan Paecharoenchai ◽  
Tittaya Suksamran ◽  
Tanasait Ngawhirunpat ◽  
Theerasak Rojanarata ◽  
Praneet Opanasopit

Chitosan nanoparticles were prepared by crosslinking chitosan (CS) with tripolyphosphate (TPP) solution using electrohydrodynamic spraying technique. The effects of CS and TPP concentration as well as electrical potential on particle size and shape were investigated. Appropriated formulations for preparing nanoparticles were chosen to encapsulate DNA. In vitro evaluation of the obtained nanoparticles as gene carrier such as entrapment efficiency and DNA release was performed. The results showed that 2 mg/ml TPP was dropped at 10 kV into 1 mg/ml CS (MW 20 kDa (F1) and 200 kDa (F2)) yielded the spherical shape and small particles of 227.67 and 240.33 nm, respectively. In DNA entrapment study, all formulations were tested by altering DNA loading to 10, 25 and 50 mg/g of CS. The results revealed that F1 with initial DNA 10 mg/g of CS showed the highest entrapment efficiency of 95.31%. While F2 with initial DNA of 25 mg/g of CS showed the highest entrapment efficiency of 89.16%. The DNA release study from CS nanoparticles indicated that the increasing of DNA amount slowed down the release rate. F1 and F2 with the initial DNA of 10 mg/g of CS had faster release rate than those with 25 and 50 mg/g of CS. It can be concluded that F1 yielded the nanoparticles with the smallest size, high DNA entrapment efficiency and enabled DNA sustained release.


2020 ◽  
Vol 35 (2) ◽  
pp. 77-91
Author(s):  
Fahad Pervaiz ◽  
Madiha Saleem ◽  
Akram Ashames ◽  
Sahrish Rehmani ◽  
Rubina Qaiser ◽  
...  

This study was designed to improve the permeability of two drugs (finasteride and minoxidil) through the skin. Finasteride-loaded poly(lactic acid- co-glycolic acid) and minoxidil-loaded chitosan nanoparticles were prepared by nanoprecipitation and ionic gelation method, respectively, and subsequently incorporated into semisolid Carbopol 940 gel. These fabricated nanoparticles were characterized for their pharmaceutical and chemical behavior. Nanoparticles were found a nearly spherical shape in the scanning electron microscopic studies and exhibited particle size in a range of 211–1012 nm. Finasteride- and minoxidil-loaded nanoparticles were optimized for relatively higher entrapment efficiency of 98% and 95%, respectively, by using the optimal concentration of polymers and stabilizers. All formulations were clear with smooth homogeneous texture and having pH values compatible with that of skin. This nanoparticulate system suspended in gel prolonged the release of drugs for up to 24 h and enhanced the drug permeability through the skin and retention of drug-loaded nanoparticles within the hair follicular routes. Therefore, these nanoparticles incorporated in the gel were found as a promising candidate for topical application in the treatment of alopecia by reducing the dosing frequency and adverse effects and as an effective strategy for improving the patient compliance toward therapy.


2019 ◽  
Vol 9 (1) ◽  
pp. 61-75 ◽  
Author(s):  
A. Dhiman ◽  
D. Bhalla

Background: Nanotechnology has gained a great deal of public interest due to the needs and applications of nanomaterials in many areas of human endeavours such as industry, agriculture, business, medicine and public health amongst many others. Polymeric nanoparticles from biodegradable and biocompatible polymers are good candidates for drug carrier to deliver the drugs because they are expected to be adsorbed in an intact form in the gastrointestinal tract after oral administration. Objective: The objective of the study was to investigate the influence of some precarious variables like, concentration of chitosan, concentration of sodium tripolyphosphate (STPP) and stirring time on physicochemical characteristics of lycopene loaded chitosan nanoparticles. Method: Eight batches of lycopene loaded chitosan nanoparticles were prepared using various concentrations of chitosan (100-200 mg), STPP (50-100 mg) by varying stirring speed in the range of 10-20 minutes using ionic gelation method. The optimized nanoparticulate formulation was characterized for various parameters like morphology study, particle size and size distribution studies, differential scanning calorimetry, entrapment efficiency and in-vitro drug release studies. Results: Lycopene loaded chitosan nanoparticles containing 150 mg of chitosan, 75 mg of STPP, 20 mg of drug lycopene and with 15 min of stirring time showed entrapment efficiency of 89.4%. The percent release of lycopene loaded chitosan nanoparticles at the end of 6 h was found to be 83.5%, however, percent release of pure lycopene at the end of 6 h was observed as 79.6%. Conclusion: Lycopene loaded chitosan nanoparticles may show a great promise for the development of drug delivery system by enhancing the cellular accumulation of lycopene with chitosan.


2020 ◽  
Vol 14 (3) ◽  
pp. 210-224
Author(s):  
Gayatri Patel ◽  
Bindu K.N. Yadav

Background: The purpose of this study was to formulate, characterize and in-vitro cytotoxicity of 5-Fluorouracil loaded controlled release nanoparticles for the treatment of skin cancer. The patents on nanoparticles (US8414926B1), (US61654404A), (WO2007150075A3) etc. helped in the selection polymers and method for the preparation of nanoparticles. Methods: In the present study nanoparticles were prepared by simple ionic gelation method using various concentrations of chitosan and sodium tripolyphosphate (TPP). Several process and formulation parameters were screened and optimized using 25-2 fractional factorial design. The prepared nanoparticles were evaluated for particle size, shape, charge, entrapment efficiency, crosslinking mechanism and drug release study. Results: The optimized 5-Fluorouracil loaded nanoparticle were found with particle size of of 320±2.1 nm, entrapment efficiency of 85.12%± 1.1% and Zeta potential of 29mv±1mv. Scanning electron microscopy and dynamic light scattering technique revealed spherical particles with uniform size. The invitro release profile showed controlled release up to 24 hr. Further study was carried using A375 basal cell carcinoma cell-line to elucidate the mechanism of its cytotoxicity by MTT assay. Conclusion: These results demonstrate that the possibility of delivering 5-Fluorouracil to skin with enhanced encapsulation efficiency indicating effectiveness of the formulation for treatment of basal cell carcinoma type of skin cancer.


2019 ◽  
Vol 9 (2) ◽  
pp. 89-96
Author(s):  
Abbaraju Krishna Sailaja ◽  
Juveria Banu

Aim: The aim of this investigation was to develop and characterize naproxen loaded chitosan nanoparticles by emulsion interfacial reaction method. Methodology: For emulsion interfacial reaction method chitosan was used as a polymer. In this method, eight formulations were prepared by varying drug to polymer concentration. Discussion: Out of eight formulations prepared using emulsion interfacial reaction method EI8 formulation was found to be the best formulation. The drug content was observed as 94.4%, entrapment efficiency and loading capacity were found to be 87.5% and 75%, respectively. The mean particle diameter was measured as 324.6nm and the Zeta potential value was found to be -42.4mv. In vitro drug release data showed 97.2% of drug release rate sustained up to 12hrs. Conclusion: The results clearly reveal that EI8 formulation having the highest amount of drug was considered as the best formulation because of its small mean particle diameter, good entrapment efficiency, and stability.


Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2302
Author(s):  
Qingwen Yu ◽  
Zhiyuan Meng ◽  
Yichao Liu ◽  
Zehao Li ◽  
Xing Sun ◽  
...  

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young’s modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.


Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 677
Author(s):  
Sara A. Abosabaa ◽  
Aliaa N. ElMeshad ◽  
Mona G. Arafa

The objective of the present research is to propose chitosan as a nanocarrier for caffeine—a commonly used drug in combating cellulite. Being a hydrophilic drug, caffeine suffers from insufficient topical penetration upon application on the skin. Chitosan nanoparticles loaded with caffeine were prepared via the ionic gelation technique and optimized according to a Box–Behnken design. The effect of (A) chitosan concentration, (B) chitosan solution pH, and (C) chitosan to sodium tripolyphosphate mass ratio on (Y1) entrapment efficiency percent, (Y2) particle size, (Y3) polydispersity index, and (Y4) zeta potential were studied. Subsequently, the desired constraints on responses were applied, and validation of the optimization procedure was confirmed by the parameters exhibited by the optimal formulation. A caffeine entrapment efficiency percent of 17.25 ± 1.48%, a particle size of 173.03 ± 4.32 nm, a polydispersity index of 0.278 ± 0.01, and a surface charge of 41.7 ± 3.0 mV were attained. Microscopical evaluation using transmission electron microscope revealed a typical spherical nature of the nanoparticles arranged in a network with a further confirmation of the formation of particles in the nano range. The results proved the successful implementation of the Box–Behnken design for optimization of chitosan-based nanoparticles in the field of advanced polymeric systems for pharmaceutical and cosmeceutical applications.


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