scholarly journals Chitosan-olive oil microparticles for phenylethyl isothiocyanate delivery: optimal formulation

2021 ◽  
Author(s):  
Ezequiel R. Coscueta ◽  
Ana Sofia Sousa ◽  
Celso A. Reis ◽  
Manuela Pintado

AbstractPhenylethyl isothiocyanate (PEITC), a chemopreventive compound, is highly reactive due to its considerably electrophilic nature. Furthermore, it is hydrophobic and has low stability, bioavailability and bioaccessibility, restricting its use in biomedical and nutraceutical or food applications. Thus, the encapsulation of this agent has the function of overcoming these limitations, promoting its solubility in water, and stabilizing it, preserving its bioactivity. So, polymeric microparticles were developed using chitosan-olive oil-PEITC systems. For this, an optimisation process (factors: olive oil: chitosan ratio and PEITC: chitosan ratio) were implemented through a central composite design. The responses were: the particle size, zeta-potential, polydisperse index, and entrapment efficiency. The optimal formulation was further characterized by FTIR and biocompatibility in Caco-2 cells. Optimal conditions were olive oil: chitosan and PEITC: chitosan ratios of 1.46 and 0.25, respectively. These microparticles had a size of 629 nm, a zeta-potential of 32.3 mV, a polydispersity index of 0.329, and an entrapment efficiency of 98.49%. We found that the inclusion process affected the optical behaviour of the PEITC, as well as the microparticles themselves and their interaction with the medium. Furthermore, the microparticles did not show cytotoxicity within the therapeutic values of PEITC. Thus, PEITC was microencapsulated with characteristics suitable for potential biomedical, nutraceutical and food applications.

2020 ◽  
Vol 17 (1) ◽  
pp. 172-183
Author(s):  
Nandanwadkar Shrikrishna Madhukar Hema ◽  
Mastiholimath Vinayak Shivamurthy ◽  
Pulija Karunakar

Introduction: Capsaicin (8-methy-N-vanillyl-6-nonenamide), a potential analgesic derived from Capsicum annuum (Chili peppers), widely used from ancient times for its pharmacological activities such as anti-inflammatory, anti-oxidant and analgesic and provides relief from migraine and diabetes. But for obvious reasons, capsaicin cannot be administered directly. The present work was designed with a focus to comply with mandatory requirement in various pharmacopeias to know the actual content of API present in final formulations. The formulation (TS3) consisting of 3% lipid, with 4:6 ratio of the polymer and solvent, was found to be the optimized formulation, which gave the best evaluation with regard to the particle size (97.03±2.68) nm, polydispersity index (0.20±0.00), higher zeta potential (61.28±2.06) mv, morphological studies and highest drug entrapment efficiency (68.34±4.24)%. The prepared transferosome formulation was subjected to characterization by validated HP-TLC method consisting of N-Hexane: Tert- Iso-butyl-methyl ether in ratio (5:15) v/v. Linearity was performed in the range of 50-1500 ng/spot with LOD/LOQ 50 ng and 150 ng, with regression analysis (R) of 99.91%. Recovery analysis was performed at 3 different levels at 80, 100 and 120 with an average recovery of 106.97%, respectively. Till now, no analytical method has been reported, associated with the characterization of pharmaceutical nano-forms (Capsaicin), like transferosomes. Thus, the maiden validated HP-TLC method for concurrent analysis of capsaicin as API in nano-transferosome may be employed in process quality control of formulations containing the said API. Background: The irritability and adverse effects post application, leading to inflammation and neural pain at the site of administration of newly Capsaicin API and its chemical entities and marketed formulations are usually related to poor permeability, leading to drug complex reactions in the development phases or therapeutic failure along with the quantification of the same in blood plasma. However, advancement in drug formulations with the use of polymer: alcohol ratio and modernized analytical techniques for the quantification of Pharmaceutical APIs seems to be emerging and promising for overcoming pain and related inflammatory complications by formulating the APIs in Transferosome formulation with Validated HP-TLC technique being used as an effective economic and precise tool for quantitative analysis of APIs in their respective nano-forms. Objective: The study proposes a novel standardized method development and validation of pharmaceutical nanoforms with Capsaicin as API. Method: Capsaicin Transferosomes were formulated using Ultra probe sonication by utilizing different proportions of phospholipid 90G dissolved in a mixture of ethanol and propylene glycol. The formulation was subjected to Dynamic Light Scattering (DLS) technique for nano-particle analysis followed by characterization with respect to particle size, polydispersity index, zeta potential and entrapment efficiency. The morphological study of vesicles was determined using SEM and TEM. A Validated HP-TLC method for the identification and determination of Capsaicin in transferosomes formulation was performed as per the ICH guidelines. Results: The formulation gave the best evaluation for particle size (97.03±2.68) nm, polydispersity index (0.20±0.00), higher zeta potential (61.28±2.06) mv, morphological studies (SEM & TEM) and highest drug entrapment efficiency (68.34±4.24)%. DSC thermograms and FTIR spectral patterns confirmed no physical interaction by polymers with API. The prepared formulation was then characterized using HP-TLC method. The best resolution was found in NHexane: Tert-Isobutyl methyl ether in a ratio of 5:15 v/v. The Rf was found to be 0.3±0.03. Linearity was performed in a range of 50-1500 ng/spot, with regression analysis (R) of 99.91% Further, recovery analysis was done at 3 different levels as 80, 100 and 120 with an average recovery of 106.97%. The LOD/LOQ was found to be 50 and 150 ng, respectively. Precision was carried out in which % RSD was found to be precise and accurate. Conclusion: The outcomes of the present study suggested that the proposed novel formulation analyzed by Validated planar chromatographic technique (HP-TLC) for Capsaicin quantification in nanoforms may be employed as a routine quality control method for the said API in various other formulations.


Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 923
Author(s):  
Shadab Md ◽  
Nabil A. Alhakamy ◽  
Hibah M. Aldawsari ◽  
Mohammad Husain ◽  
Nazia Khan ◽  
...  

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ±6.0 and 79.43 ± 12.43 µg/ cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.


Author(s):  
RISA AHDYANI ◽  
LARAS NOVITASARI ◽  
RONNY MARTIEN

Objective: The objectives of this study were to formulate and characterize nanoparticles gel of timolol maleate (TM) by ionic gelation method using chitosan (CS) and sodium alginate (SA). Methods: Optimization was carried out by factorial design using Design Expert®10.0.1 software to obtain the concentration of CS, SA, and calcium chloride (CaCl2) to produce the optimum formula of TM nanoparticles. The optimum formula was characterized for particle size, polydispersity index, entrapment efficiency, Zeta potential, and molecular structure. Hydroxy Propyl Methyl Cellulose (HPMC) K15 was incorporated into optimum formula to form nanoparticles gel of TM and carried out in vivo release study using the Franz Diffusion Cell. Results: TM nanoparticles was successfully prepared with concentration of CS, SA, and CaCl2 of 0.01 % (w/v), 0.1 % (w/v), and 0.25 % (w/v), respectively. The particle size, polydispersity index, entrapment efficiency, and Zeta potential were found to be 200.47±4.20 nm, 0.27±0.0154, 35.23±4.55 %, and-5.68±1.80 mV, respectively. The result of FTIR spectra indicated TM-loaded in the nanoparticles system. In vitro release profile of TM-loaded nanoparticles gel showed controlled release and the Korsmeyer-Peppas model was found to be the best fit for drug release kinetics. Conclusion: TM-loaded CS/SA nanoparticles gel was successfully prepared and could be considered as a promising candidate for controlled TM delivery of infantile hemangioma treatment.


2021 ◽  
Vol 17 ◽  
Author(s):  
Swayamprakash Patel ◽  
Ashish Patel ◽  
Mruduka Patel ◽  
Umang Shah ◽  
Mehul Patel ◽  
...  

Background: Probe sonication and High-speed homogenizer are comparatively costly equipment to fabricate the nanoparticles. Many academic and research institutions cannot afford the procurement and maintenance of such sophisticated equipment. In the present work, a newer idea is conceptualized, which can be adopted by the underprivileged research institutions to fabricate solid lipid nanoparticles (SLN) in the absence of sophisticated equipment. The current work describes the pilot-level trials of this novel approach. This study represents the preliminary proof-of-concept trials for which the Indian patent application (3508/MUM/2015) is filed. Method: A frugal piece of equipment was made using a 50 ml centrifuge tube with conical bottom and a piezoelectric mist maker or humidifier. SLNs were prepared by combining the quasi-emulsion solvent evaporation approach and ultrasonic vibration approach. A quasi-emulsion was composed by the dropwise mixing of the organic solvent containing drug & lipid with an aqueous solution containing surfactant under continuous ultrasonic vibration in the piezoelectric chamber. The size of the droplets was significantly reduced due to piezoelectric ultrasonic vibration. Under the provision of mild vacuum and heat generated by vibration, the organic solvent was evaporated, which leaves behind a suspension of SLN. In the present work, albendazole was selected as a model drug. Various trials with Compritol 888 ATO® and Precirol ATO 5® as a lipid carrier and Tween 80 and Poloxamer 188 as a surfactant were performed. Zeta potential of SLNs was improved by the addition of polyelectrolytes like K2SO4 and Na4P2O7. Result and Conclusion: The ratio of drug to lipid was optimized to 1:4 for the most favorable results. SLN with a minimum Z-average diameter of 98.59 nm, -21 mV zeta potential, and 34.064 % (SD 10.78, n=9) entrapment efficiency were developed using the Precirol ATO 5 ® as a lipid carrier. The proof of concept for this novel approach is established through the development of Albendazole SLNs. This approach must also be evaluated for the development of polymeric nanoparticles and vesicular formulations. The further sophistication of the frugal equipment may allow more control over the quality of SLN. This approach will enable underprivileged researchers to prepare Nanopharmaceuticals. Researchers and students of such institutions can focus on the application of SLN by resolving the constraint of sophisticated equipment with this novel approach. This novel approach should also be tried for polymeric and vesicular nanopharmaceuticals.


Author(s):  
Mohammad Reza Mehrabi ◽  
Mohammad Ali Shokrgozar ◽  
Tayebeh Toliyat ◽  
Masoomeh Shirzad ◽  
Azadeh Izadyari ◽  
...  

: Clinical application of vincristine sulfate as a chemotherapeutic agent is limited because of its low aqueous solubility and severe side effects. This study aimed to improve the bioavailability and reduce side effects of vincristine sulfate through entrapping in PEGylated niosomes. We evaluated the anticancer activity of PEGylated niosomal vincristine sulfate (PEG-nVCR) in a mouse model of lymphoma induced by BCL1 clone 5B1b cell line. PEG-nVCR was prepared by the thin-film hydration method. The prepared niosomes were characterized by size, zeta potential, and entrapment efficiency. The drug release pattern, neurotoxicity experiment, and in vivo anticancer activity of PEG-nVCR were evaluated by the dialysis diffusion method, rotarod performance test, and flow cytometry, respectively. The mean particle size, zeta potential, and entrapment efficiency of nisomes were obtained around 220 nm, -19 mV, and 81%, respectively. A sustained release behavior was indicated by PEG-nVCR so that the maximum release of VCR from niosomes reached to 69% after 36h of incubation. After the treatment of mice by different formulations, a significant reduction in lymphoma cells in the spleen was obtained for the PEG-nVCR, as compared to the free vincristine sulfate. In the neurotoxicity experiment, a 2.5-fold lower motor incoordination effect was observed for the PEG-nVCR group with respect to the free VCR group. According to these findings, it can be concluded that the PEGylated niosomal formulation could be a suitable carrier for the delivery of VCR to the lymphoma cells or other related cancer cells.


Author(s):  
Marwa H. Abdallah ◽  
Amr S. Abu Lila ◽  
Md. Khalid Anwer ◽  
El-Sayed Khafagy ◽  
Muqtader Mohammad ◽  
...  

The present work was aimed to develop a transferosomal gel of ibuprofen (IBU) for the amelioration of psoriasis like inflammation. Three formulation of IBU loaded transferosomes (TFs1-TFs3) were prepared using different proportions of lipid (phospholipon 90H) and surfactant (tween 80) and further evaluated for vesicle size, zeta potential (ZP), entrapment efficiency and in vitro drug release. The IBU loaded transferosomes (TFs2) was optimized with vesicle size (217±8.4 nm), PDI (0.102), ZP (-31.5±4.3 mV), entrapment efficiency (88.4±6.9%) and drug loading (44.2±2.9%). Further, the optimized IBU loaded transferosomes (TFs2) was incorporated into 1% carbopol 934 gel base and characterized for homogeneity, extrudability, viscosity and drug content. The in vivo pharmacodynamic study of gel exhibited reduction in psoriasis like inflammation in mice. The ibuprofen loaded transferosomal gel was successfully developed and has shown the potential to be a new therapy against psoriasis like inflammation.


Author(s):  
Haithem N Abed ◽  
Ahmed A. Hussein

Abstract The purpose of our study was to develop Dabigatran Etexilate loaded nanostructured lipid carriers (DE-NLCs) using Glyceryl monostearate and Oleic acid as lipid matrix, and to estimate the potential of the developed delivery system to improve oral absorption of low bioavailability drug, different Oleic acid ratios effect on particle size, zeta potential, entrapment efficiency and loading capacity were studied, the optimized DE-NLCs shows a particle size within the nanorange, the zeta potential (ZP) was 33.81±0.73mV with drug entrapment efficiency (EE%) of  92.42±2.31% and a loading capacity (DL%) of 7.69±0.17%. about 92% of drug was released in 24hr in a controlled manner, the ex-vivo intestinal permeation study using the non-everted sac model shows four folds increment in the permeation of DE-NLCs compared to dabigatran etexilate suspension (DE-S).


Author(s):  
Deepti Dwivedi ◽  
Shubham Pandey ◽  
Shafaque Asif ◽  
Vineet Awasthi ◽  
Gurjeet Kaur ◽  
...  

Objective: The present research work was undertaken to develop quercetin enthused nanolipoidal systems and its characterization. The objective was to investigate potential of prepared system in the management of DNCB induced dermatitis. Method: Nanolipoidal system was prepared in different combinations with quercetin, L-α phosphatidylcholine (SPC) and ethanol and characterized for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, percentage drug release, skin retention and skin permeation. Selected batches were further incorporated into Carbopol 934 base gel. The vesicles were in size range 324.19-359 nm while polydispersity index (PDI) ranges from 0.241-0.554 and for zeta potential, it was from -26.33 to -39.3 nm. Entrapment efficiency was from 23.77-94.68 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin up to 45.23 µm which was significantly higher than the rhodamine solution (10 µm). In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed a marked decrease in amount of inflammatory cell nucleus in mice treated with quercetin loaded ethosomal gel followed by 76.13% decrease in-ear swelling and ear mass respectively in morphology study. The conventional marketed formulation showed a nominal decrease in epidermal thickness. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Results: The optimized formulation F6 with SPC and ethanol in the ratio of 20:80 displayed the highest drug content and entrapment efficiency of 94.68±1.14%. PDI was 0.241±0.11 and skin retention 7.7%. Batch F6 with vesicle size and zeta potential of 324.9±19 nm and -26.33 mV, respectively, was incorporated in Carbopol 934 base gel and the prepared gel was evaluated for morphology, spreadability, in vitro, ex vivo release study, and kinetics study and in vivo studies. Conclusion: The present study revealed that the developed ethosomal gel can be used for enhanced delivery of Quercetin via skin. The in vitro studies indicated that the gel serves as an efficient carrier for Quercetin. It showed its effectiveness in the management of dermatitis. Further, Quercetin loaded nanoethosomal gel formulation can be viewed as a promising drug delivery system for the management of dermatitis.


Author(s):  
RADITYA ISWANDANA ◽  
RICHA NURSELVIANA ◽  
SUTRIYO SUTRIYO

Objective: Gold nanoparticles (AuNPs) are highly useful for drug delivery, but their application is limited by their stability as they readily aggregate.This issue can be prevented by adding a stabilizing agent such as resveratrol (RSV), which is a polyphenol derived from plants, that is used to preventcancer. Therefore, we propose a novel method to prepare stable RSV-conjugated nanoparticles modified with polyethylene glycol (RSV-AuNP-PEG).Methods: In the first step, the Turkevich method was used to synthesize the AuNPs. Then, PEG was added as stabilizer agent and conjugated with RSV.The synthesized conjugates were characterized using ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, particle sizeanalysis, and high-performance liquid chromatography.Results: The obtained RSV-AuNP-PEG had a particle size of 83.93 nm with a polydispersity index (PDI) of 0.562 and formed a translucent purple-redfluid in solution. The zeta potential was −22.9 mV, and the highest entrapment efficiency was 75.86±0.66%. For comparison, the RSV-AuNP solutionwas purple and turbid, the particle size was 51.97 nm with a PDI of 0.694, and the zeta potential was −24.6 mV. The stability test results showed thatthe storage stability of RSV-AuNP-PEG was better than that of AuNP-RSV. Further, the RSV-AuNP-PEG was shown to be most stable in 2% bovine serumalbumin (BSA) while the AuNP-RSV was most stable in 2% BSA in phosphate-buffered saline pH 7.4.Conclusion: These results show that modification of RSV-conjugated AuNPs with PEG effectively prevents their aggregation in storage, but only incertain mediums.


Author(s):  
M. Yasmin Begum ◽  
Prathyusha Reddy Gudipati

Objective: The aim of present work was to formulate and evaluate Dasatinib (DST) loaded solid lipid nanoparticles (SLNs) as a potential anticancer drug delivery system by enhancing its solubility.Methods: SLNs consist of a solid lipid matrix where the drug was incorporated. Surfactants of GRAS grade were used to avoid aggregation and to stabilize the SLNs. DST-SLNs formulations of varying concentrations were prepared by high speed homogenization technique and evaluated for drug excipients compatibility study, poly-dispersity index, particle size analysis, surface morphology, zeta potential and drug release features.Results: It was observed that DST-SLNs with optimum quantities of poloxomer: lecithin ratio showed 88.06% drug release in 6h with good entrapment efficiency of 76.9±0.84 %. Particle size, Poly dispersity index, zeta potential and drug entrapment efficiency for the optimized formulation was found to be optimum. Stability studies revealed that the entrapment efficiency of the SLN dispersion stored in 4 °C was stable.Conclusion: Thus, it can be concluded that formulations of DST loaded SLNs are suitable carriers for improving the solubility and dissolution related problems. 


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