scholarly journals Different Approaches to the Synthesis and Applications of Biomedical and Pharmaceutical Smart Biomaterials

Author(s):  
Mohamed Mahmoud Khattab

In this study, two strategies were used to functionalize cellulose nanowhiskers. Firstly, by grafting its surface with β-cyclodextrin (βCD) for developing drug-nanocarrier. Secondly, by conjugating short polymer segments to its surface for reinforcing Poly(Ɛ-Caprolactone) (PCL), in order to develop nanocomposites with promoted properties suitable for regenerative medicine. In addition, the production and recovery of biodegradable bioplastics poly(3-hydroxybutyrate) (P(3HB)) from agro-industrial residues of hemp hurd biomass was also examined. In the first part, a drug-nanocarrier system based on βCD-grafted bacterial cellulose nanowhisker (BCNC-g-βCD) was developed as a prolonged drug release nanocarrier. Antibiotic Ciprofloxacin (CIP) and anticancer drugs; Doxorubicin (DOX) and Paclitaxel (PTX) were conjugated to BCNC-g-βCD as model drugs to form the drug-nanocarrier (BCNC-g-βCD-drug). Compared with un-grafted BCNC, the developed drug-nanocarrier showed significant increase in drug payloads from 495 ±4 to 810 ±7 µg/mg along with radical improvement in the drug release profiles. Initial burst releases was reduced significantly and prolonged and sustained release for (74.5–90%) of drug payload over 4–5.5 days were observed. In addition, an improved drug release performances were pragmatic in acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data pointed to zero-order kinetic model with estimated zero-order release constants (K0) of 0.68, 0.74, and 0.79 µg drug/h (at pH 6.4, 37°C) for BCNC-g-βCD-CIP, BCNC-g-βCD-DOX and BCNC-g-βCD-PTX nanosystems, respectively. In the second part, the functionalized bacterial cellulose nanowhisker (BCNW-g-βCD-PCL2000) was synthesized. Reinforcing PCL matrix with 4 wt% of the functionalized nanowhisker resulted in bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite showed 115% and 51% improvements in tensile strength and Young’s modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous strutures having porosity of 86-95% and interconnected macropores with mean pore diameters of 250-420 µm. Porous scaffolds showed compression moduli values of 5.3-9.1 MPa in the range of cancellous bones. In the third part a dual-function PCL scaffold was fabricated. The envisioned drug-laden scaffold would provide adequate structural and mechanical supports for the newly regenerated tissues and simultaneously serve as localized drug delivery system. In this context, reinforced PCL with 4 wt% of BCNW-g-βCD-PCL2000 and 25 wt% of doxorubicin anticancer drug resulted in drugladen bionanocomposite of combined promoted bulk properties. Improvements of 165% and 107% in tensile strength and Young’s modulus, respectively; 31% in hydrophilicity; 10% in degradation rate; and 8°C increases in thermal stability. The obtained drug-laden porous scaffolds showed compressive moduli in the range of 7.2-12.3 MPa. In vitro drug releases fit the first-order release mechanism and occurred in a diffusion-controlled and sustained manner 60 days without obvious burst releases. The scaffolds will ultimately minimize systemic toxicities of drugs, lessen the number of dosing, and diminish the need for removal procedure. The forth study described prospective trials for greener production and extraction of the biodegradable bioplastics poly(3-hydroxybutyrate) P(3HB) from agro-industrial residues of hemp hurd biomass. Results showed that maximum hydrolysis yield of 72.4% was achieved by alkali pretreatment with 2% NaOH at 135°C for 60 min along with two-step enzymatic hydrolysis and ultrasonication. Total hydrolysate sugar concentration of 53.0 g/L was obtained. Under optimum conditions, total P(3HB) production of 13.4 g/L was achieved within 80 h of fermentation. Ultrasonic-assisted sodium dodecyl sulfate (SDS) has showed effectiveness as economic recovery method. It recovered bioplastics directly from the broth cell concentrate with P(3HB) content of 92%. Number average molecular weights (Mn) of recovered bioplastics were in the range of 150–270 kDa with polydispersity index (Mw/Mn) of 2.1–2.4.

2021 ◽  
Author(s):  
Mohamed Mahmoud Khattab

In this study, two strategies were used to functionalize cellulose nanowhiskers. Firstly, by grafting its surface with β-cyclodextrin (βCD) for developing drug-nanocarrier. Secondly, by conjugating short polymer segments to its surface for reinforcing Poly(Ɛ-Caprolactone) (PCL), in order to develop nanocomposites with promoted properties suitable for regenerative medicine. In addition, the production and recovery of biodegradable bioplastics poly(3-hydroxybutyrate) (P(3HB)) from agro-industrial residues of hemp hurd biomass was also examined. In the first part, a drug-nanocarrier system based on βCD-grafted bacterial cellulose nanowhisker (BCNC-g-βCD) was developed as a prolonged drug release nanocarrier. Antibiotic Ciprofloxacin (CIP) and anticancer drugs; Doxorubicin (DOX) and Paclitaxel (PTX) were conjugated to BCNC-g-βCD as model drugs to form the drug-nanocarrier (BCNC-g-βCD-drug). Compared with un-grafted BCNC, the developed drug-nanocarrier showed significant increase in drug payloads from 495 ±4 to 810 ±7 µg/mg along with radical improvement in the drug release profiles. Initial burst releases was reduced significantly and prolonged and sustained release for (74.5–90%) of drug payload over 4–5.5 days were observed. In addition, an improved drug release performances were pragmatic in acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data pointed to zero-order kinetic model with estimated zero-order release constants (K0) of 0.68, 0.74, and 0.79 µg drug/h (at pH 6.4, 37°C) for BCNC-g-βCD-CIP, BCNC-g-βCD-DOX and BCNC-g-βCD-PTX nanosystems, respectively. In the second part, the functionalized bacterial cellulose nanowhisker (BCNW-g-βCD-PCL2000) was synthesized. Reinforcing PCL matrix with 4 wt% of the functionalized nanowhisker resulted in bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite showed 115% and 51% improvements in tensile strength and Young’s modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous strutures having porosity of 86-95% and interconnected macropores with mean pore diameters of 250-420 µm. Porous scaffolds showed compression moduli values of 5.3-9.1 MPa in the range of cancellous bones. In the third part a dual-function PCL scaffold was fabricated. The envisioned drug-laden scaffold would provide adequate structural and mechanical supports for the newly regenerated tissues and simultaneously serve as localized drug delivery system. In this context, reinforced PCL with 4 wt% of BCNW-g-βCD-PCL2000 and 25 wt% of doxorubicin anticancer drug resulted in drugladen bionanocomposite of combined promoted bulk properties. Improvements of 165% and 107% in tensile strength and Young’s modulus, respectively; 31% in hydrophilicity; 10% in degradation rate; and 8°C increases in thermal stability. The obtained drug-laden porous scaffolds showed compressive moduli in the range of 7.2-12.3 MPa. In vitro drug releases fit the first-order release mechanism and occurred in a diffusion-controlled and sustained manner 60 days without obvious burst releases. The scaffolds will ultimately minimize systemic toxicities of drugs, lessen the number of dosing, and diminish the need for removal procedure. The forth study described prospective trials for greener production and extraction of the biodegradable bioplastics poly(3-hydroxybutyrate) P(3HB) from agro-industrial residues of hemp hurd biomass. Results showed that maximum hydrolysis yield of 72.4% was achieved by alkali pretreatment with 2% NaOH at 135°C for 60 min along with two-step enzymatic hydrolysis and ultrasonication. Total hydrolysate sugar concentration of 53.0 g/L was obtained. Under optimum conditions, total P(3HB) production of 13.4 g/L was achieved within 80 h of fermentation. Ultrasonic-assisted sodium dodecyl sulfate (SDS) has showed effectiveness as economic recovery method. It recovered bioplastics directly from the broth cell concentrate with P(3HB) content of 92%. Number average molecular weights (Mn) of recovered bioplastics were in the range of 150–270 kDa with polydispersity index (Mw/Mn) of 2.1–2.4.


Author(s):  
Dillip Kumar Behera ◽  
Kampal Mishra ◽  
Padmolochan Nayak

In this present work, chitosan (CS) crosslink with polyaniline (PANI) with montmorilonite (MMT) called as (CSPANI/MMT) and CS crosslink with PANI without MMT called as (CS-PANI) were prepared by employing the solution casting method. Further the formation of nanocomposites CS-PANI/MMT and CS-PANI were investigated using XRD, FTIR, SEM and tensile strength. Water uptake and swelling ratio of the CS-PANI and CS-PANI/MMT were found to decrease with increase in concentration of clay. Mechanical properties of the CS-PANI and CS-PANI/MMT were assessed in terms of tensile strength and extensibility using texture analyzer. Increase in tensile strength and reduction in extensibility was reported with increase in the nanoclay content. In vitro drug release study on CS-PANI and CS-PANI/MMT indicated pronounced sustained release of doxorubicin by the incorporation of clay particles in the CS polymer matrix. Overall CSPANI/MMT nanocomposite films exhibited improved mechanical and sustained drug release properties than CS-PANI.


Author(s):  
Bhikshapathi D. V. R. N. ◽  
Arun Kumar Jarathi ◽  
Suresh Gande ◽  
Viswaja Medipally ◽  
Ramesh Bomma

Background and the purpose of the study: Risedronate sodium inhibits osteoclast bone resorption and modulates bone metabolism. Risedronate has a high affinity for hydroxyapatite crystals in bone and is a potent antiresorptive agent. In the present investigation efforts were made to improve the bioavailability of risedronate sodium by increasing the residence time of the drug through sustained-release matrix capsule formulation via gastroretentive mechanism. Capsules were prepared by wet granulation technique. The influence of gel forming agents, amount of risedronate and total weight of capsules on physical properties, in vitro buoyancy, drug release, FTIR, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study at 40 °C/75% RH, 25 °C/60% RH for the period of three months. For all formulations, kinetics of drug release from capsules followed Higuchi’s square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulation containing 25 mg HPMC K4M and 75 mg HPMC K100 LV (F-8) showed zero order release profile. There was no significant change in the selected formulation, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.60 ± 0.77 hrs for the selected formulation. Stable, sustained release effervescent floating capsules of risedronate sodium could be prepared by wet granulation technique.  


2020 ◽  
Vol 15 ◽  
Author(s):  
Balaji Maddiboyina ◽  
Vikas Jhawat ◽  
Gandhi Sivaraman ◽  
Om Prakash Sunnapu ◽  
Ramya Krishna Nakkala ◽  
...  

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl were prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium sterate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification, In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson–crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in acceptable range for all formulations. Based on the In vitro dissolution profile, formulation F-9 was considered to be the optimized extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and also compared with innovator product (flavix XR) showed better drug release profile. Conclusion: The core-in-cup technology has a potential to control the release rate of freely water soluble drugs for single administration per day by optimization with combined use of hydrophilic and hydrophobic polymers.


2007 ◽  
Vol 336-338 ◽  
pp. 1545-1548
Author(s):  
Lin Luo ◽  
Guang Fu Yin ◽  
Yun Zhang ◽  
Ya Dong Yao ◽  
Wei Zhong Yang ◽  
...  

Porous biodegradable scaffolds are widely used in bone tissue engineering to provide temporary templates for cellular attachment and matrix synthesis. Ideally, the degradation rate in vivo may be similar or slightly less than that of tissue formation, allowing for the maintenance of the scaffold structure and the mechanical support during early stages of tissue formation. Eventually, the 3-D spaces occupied by the porous scaffolds will be replaced by newly formed tissue. In this work, β-tricalcium phosphate/Poly-L lactide (β-TCP/PLLA) scaffolds with different proportions of β-TCP to PLLA were investigated. The effects of β-TCP proportions on degradation rate and mechanical strengths of the scaffolds were evaluated in simulated body fluid (SBF) at 37°C up to 42 days. Results show that: different proportions of β-TCP to PLLA have significant influence on degradation behaviors of the scaffolds, and mechanical strengths of the scaffolds with weight proportion of β-TCP to PLLA being 2 to 1 are much higher than those of the others during the degradation period. And in this period, the scaffolds biodegrade slowly, and Hydroxyl Carbonate Apatite (HCA) forms in the surface of the material.


2021 ◽  
Vol 7 (1) ◽  
pp. 35-38
Author(s):  
Sudipta Das ◽  
Arnab Samanta ◽  
Koushik Bankura ◽  
Debatri Roy ◽  
Amit Nayak

The present work is focused on the preparation and in vitro release kinetics of liposomal formulation of Leuprolide Acetate. In this work, “Thin Lipid Film Hydration Method” was used for preparation of Leuprolide Acetate loaded liposomes. Prepared liposomal formulations of Leuprolide acetate was evaluated by drug entrapment study, in-vitro drug release kinetics and stability studies. The percentage drug entrapment of Leuprolide acetate for F1 and F2 formulations were found to be 78.14 ± 0.67 and 66.70 ± 0.81% respectively. In-vitro drug release study of liposomal formulations had shown zero order release pattern. Regression co-efficient (R2) value of Zero order kinetics for F1 and F2 formulations were 0.9912 and 0.9676 respectively. After storing formulations for 1 month, stability testing was done at 40C.It was found that all batches were stable. These liposomal formulations of Leuprolide acetate can be formulated for parenteral application to treat prostate cancer and in women, to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Rajni Bala ◽  
Sushil Khanna ◽  
Pravin Pawar

Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of Cmax (95.87%), tmax (71.42%), AUC0−t (98.125%), and AUC0−∞ (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles.


2017 ◽  
Vol 9 (6) ◽  
pp. 85
Author(s):  
G. Ravi ◽  
N. Vishal Gupta

Objective: The objective of present investigation was to develop rivastigmine tartrate transdermal film employing factorial design.Methods: The formulations were designed by Design-Expert software-version10. A series of films were prepared by solvent casting method using polymers, plasticizer, permeation enhancer and other solvents. Transdermal films were evaluated for flatness, drug content, tensile strength, in vitro drug release and ex vivo skin permeation study.Results: The flatness was found 100% (percentage) for all film formulations. The drug content of transdermal film was found in the range of 96.51±0.2 to 98.81±0.3%. The tensile strength of transdermal film was found in the range of 6.28±0.06 to 11.56±0.03 N/mm2 (newton/millimeter2) and in vitro drug release at 24th h (hour) was found in the range of 86.24±0.25 to 96.1±0.48%% for various formulations and ex vivo skin permeation study results at 24th h was found in the range of 85.83±0.74 to 97.36±0.93%.Conclusion: These results support the feasibility of developing transdermal film of rivastigmine tartrate for human applications. Thus, transdermal delivery of rivastigmine tartrate film is a safe, painless and cost effective drug delivery system for Alzheimer’s patients.


2020 ◽  
Author(s):  
Xingyu He ◽  
Zheng Yuan ◽  
Samantha Gaeke ◽  
Winston W.-Y. Kao ◽  
S. Kevin Li ◽  
...  

AbstractThe current standard of care for posterior segment eye diseases, such as age-related macular degeneration and diabetic macular edema, is frequent intravitreal injections or sustained-release drug implants. Drug implants have side effects due to the burst release of the drugs, and their release cannot be easily controlled after implantation. Present study attempts to develop a dosage-controllable drug delivery implant which consists of a nanoporous biodegradable PLGA capsule and light-activated liposomes. Controllable drug release from the implant was achieved by using pulsed near-infrared (NIR) laser both in vitro and in vivo. The in vitro drug release kinetics from two different initial dose implants, 1000 μg and 500 μg, was analyzed by fitting zero order and first order kinetics, as well as the Korsmeyer-Peppas and Higuchi models. The 1000 μg and 500 μg implants fit the first-order and zero-order kinetics model, respectively, the best. The multiple drug releases in the vitreous was determined by in vivo fluorimeter, which was consistent with the in vitro data. The dose released was also clinically relevant. Histology and optical and ultrasound imaging data showed no abnormality in the eyes received implant treatment suggesting that the drug delivery system was safe to the retina. This on-demand dose-controllable drug delivery system could be potentially used for long-term posterior eye disease treatment.


Author(s):  
Roshan K Pawar ◽  
Kalaiselvan S ◽  
Balamurugan K

The intention of this current study is to intensify the bioavailability of drugs which have lower bioavailability (<20 %) like Lovastatin in the form of NLC carrier and also to optimize the formulation to select perfect variables for the formulation. The Nanostructures lipid carrier was formulated using Hot Homogenization technique with some optimization by utilizing 23 factorial design with the heal of response like in-vitro drug release, % Entrapment Efϑiciency (EE%), % drug Content (%DC), Zeta potential (Zp), Polydispersity Index (PI) and Particle Size (PS) for 12 hours. The kinetic studies of in-vitro drug release was performed and the parameters of the drug in different kinetic models like higuchi kinetic, zero order, ϑirst order, peppas models were evaluated. Invitro release kinetics studies show that optimized formulation NLC (N3) obeys Super Case II kinetics transport mechanism i.e., release of drug through reduction of attractive forces between Lipid chains and Zero order release kinetics for controlled drug delivery. Hence Nanostructure lipid carrier shows a good control and predetermined rate of drug release of Lovastatin. From the obtained outcome, N3 formulation was concluded as an optimized formulation with selected formulation variables like Solid Lipid: Liquid Lipid ratio (6:4), Span 80 as Surfactant (1%) and process variables like homogenization Speed as 5000 Rotations per minute for 15 mins.><20 %) like Lovastatin in the form of NLC carrier and also to optimize the formulation to select perfect variables for the formulation. The Nanostructures lipid carrier was formulated using Hot Homogenization technique with some optimization by utilizing 23 factorial design with the heal of response like in-vitro drug release, % Entrapment Efficiency (EE%), % drug Content (%DC), Zeta potential (Zp), Polydispersity Index (PI) and Particle Size (PS) for 12 hours. The kinetic studies of in-vitro drug release was performed and the parameters of the drug in different kinetic models like higuchi kinetic, zero order, first order, peppas models were evaluated. Invitro release kinetics studies show that optimized formulation NLC (N3) obeys Super Case II kinetics transport mechanism i.e., release of drug through reduction of attractive forces between Lipid chains and Zero order release kinetics for controlled drug delivery. Hence Nanostructure lipid carrier shows a good control and predetermined rate of drug release of Lovastatin. From the obtained outcome, N3 formulation was concluded as an optimized formulation with selected formulation variables like Solid Lipid: Liquid Lipid ratio (6:4), Span 80 as Surfactant (1%) and process variables like homogenization Speed as 5000 Rotations per minute for 15 mins.


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