Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation

Treatment of pulmonary infections caused by Mycobacterium abscessus are extremely difficult to treat, as this species is naturally resistant to many common antibiotics. Liposomes are vesicular nanocarriers suitable for hydrophilic and lipophilic drug loading, able to deliver drugs to the target site, and successfully used in different pharmaceutical applications. Moreover, liposomes are biocompatible, biodegradable and nontoxic vesicles and nebulized liposomes are efficient in targeting antibacterial agents to macrophages. The present aim was to formulate rifampicin-loaded liposomes (RIF–Lipo) for lung delivery, in order to increase the local concentration of the antibiotic. Unilamellar liposomal vesicles composed of anionic DPPG mixed with HSPC for rifampicin delivery were designed, prepared, and characterized. Samples were prepared by using the thin-film hydration method. RIF–Lipo and unloaded liposomes were characterized in terms of size, ζ-potential, bilayer features, stability and in different biological media. Rifampicin’s entrapment efficiency and release were also evaluated. Finally, biological activity of RIF-loaded liposomes in Mycobacterium abscessus-infected macrophages was investigated. The results show that RIF-lipo induce a significantly better reduction of intracellular Mycobacterium abscessus viability than the treatment with free drug. Liposome formulation of rifampicin may represent a valuable strategy to enhance the biological activity of the drug against intracellular mycobacteria.

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Solid Lipid Nanoparticles for Topical Delivery of Acitretin for the Treatment of Psoriasis by Design of Experiment

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2019.12.2.5 ◽

2020 ◽

Vol 12 (2) ◽

pp. 4474-4491

Author(s):

Rajkumar Aland ◽

Ganesan M ◽

P. Rajeswara Rao ◽

Bhikshapathi D. V. R. N.

Keyword(s):

Particle Size ◽

Drug Release ◽

Solid Lipid Nanoparticles ◽

Drug Loading ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Tem Analysis ◽

In Vitro Drug Release ◽

Solid Lipid

The main objective for this investigation is to develop and optimize the solid lipid nanoparticles formulation of acitretin for the effective drug delivery. Acitretin loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s orthogonal array with eight parameters that could affect the particle size and entrapment efficiency. Based on the results from the analyses of the responses obtained from Taguchi design, three different independent variables including surfactant concentration (%), lipid to drug ratio (w/w) and sonication time (s) were selected for further investigation using central composite design. The lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. TEM analysis has demonstrated the presence of individual nanoparticles in spherical shape and the results were compatible with particle size measurements. In vitro drug release of optimized SLN formulation (F2) was found to be 95.63 ± 1.52%, whereas pure drug release was 30.12 after 60 min and the major mechanism of drug release follows first order kinetics release data for optimized formulation (F2) with non-Fickian (anomalous) with a strong correlation coefficient (R2 = 0.94572) of Korsemeyer-Peppas model. The total drug content of acitretin gel formulation was found to 99.86 ± 0.012% and the diameter of gel formulation was 6.9 ± 0.021 cm and that of marketed gel was found to be 5.7 ± 0.06 cm, indicating better spreadability of SLN based gel formulation. The viscosity of gel formulation at 5 rpm was found to be 6.1 x 103 ± 0.4 x 103 cp. The release rate (flux) of acitretin across the membrane and excised skin differs significantly, which indicates about the barrier properties of skin. The flux value for SLN based gel formulation (182.754 ± 3.126 μg cm−2 h−1) was found to be higher than that for marketed gel (122.345 ± 4.786 μg cm−2 h−1). The higher flux and Kp values of SLN based gel suggest that it might be able to enter the skin easily as compared with marketed gel with an advantage of low interfacial tension of the emulsifier film that ensures an excellent contact to the skin. This topically oriented SLN based gel formulation could be useful in providing site-specific dermal treatment of psoriasis

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Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽

10.3390/pharmaceutics13081210 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1210

Author(s):

Xieguo Yan ◽

Shiqiang Wang ◽

Kaoxiang Sun

Keyword(s):

Drug Loading ◽

Entrapment Efficiency ◽

In Vitro Dissolution ◽

Dissolution Behavior ◽

In Vivo Evaluation ◽

Long Term Treatment ◽

Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

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Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽

10.3390/pharmaceutics13060904 ◽

2021 ◽

Vol 13 (6) ◽

pp. 904

Author(s):

Irin Tanaudommongkon ◽

Asama Tanaudommongkon ◽

Xiaowei Dong

Keyword(s):

Sustained Release ◽

Trough Concentration ◽

Self Assembly ◽

Subcutaneous Injection ◽

Drug Loading ◽

Entrapment Efficiency ◽

Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

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Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents

Scientific Reports ◽

10.1038/s41598-017-08749-6 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 8

Author(s):

C. Zamperini ◽

G. Maccari ◽

D. Deodato ◽

C. Pasero ◽

I. D’Agostino ◽

...

Keyword(s):

Biological Activity ◽

Antibacterial Agents

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Attenuation of Aggregatibacter actinomycetemcomitans virulence using curcumin-decorated nanophytosomes-mediated photo-sonoantimicrobial chemotherapy

Scientific Reports ◽

10.1038/s41598-021-85437-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maryam Pourhajibagher ◽

Abbas Bahador

Keyword(s):

Cell Viability ◽

Metabolic Activity ◽

Antimicrobial Chemotherapy ◽

Drug Loading ◽

Entrapment Efficiency ◽

Aggregatibacter Actinomycetemcomitans ◽

Antimicrobial Activities ◽

Ultrasonic Waves ◽

Blue Laser ◽

Mrna Levels

AbstractThis study aimed to focus on the simultaneous use of antimicrobial photodynamic therapy (aPDT) and sonodynamic antimicrobial chemotherapy (SACT), which is called photo-sonodynamic antimicrobial chemotherapy (PSACT) to attenuate the virulence of Aggregatibacter actinomycetemcomitans. Following the synthesis of Curcumin-decorated nanophytosomes (Cur-NPhs) as a novel photo-sonosensitizer, its particle size, polydispersity, ζ-potential surface morphology, physical stability, drug release, and entrapment efficiency were determined. In the Cur-NPhs-PSACT, the antimicrobial activities of Cur-NPhs against A. actinomycetemcomitans were investigated using cell viability, biofilm killing/degradation, metabolic activity, expression of quorum-sensing-associated qseB and qseC genes, and biofilm-associated rcpA gene under blue laser irradiation plus ultrasonic waves. Characterization tests showed the presence of a sphere-shaped vesicle and the self-closed structure of Cur-NPhs, resulting in a high drug-loading content and encapsulation efficiency. However, the antimicrobial effect of Cur-NPhs-PSACT was dose-dependent, PSACT using the high concentrations of Cur-NPhs (50 × 10–4 g/L) showed significant reductions (P < 0.05) in cell viability (13.6 log10 CFU/mL), biofilm killing/degradation (65%), metabolic activity (89.6%,), and mRNA levels of virulence determinant genes (qseB; 9.8-fold, qseC; 10.2-fold, and recA; 10.2-fold). This study concludes that the Cur-NPhs-PSACT had antimicrobial activities against A. actinomycetemcomitans by downregulating the expression of virulence genes, and may attenuate this bacterium that decreases periodontal disease severity in patients.

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SCREENING OF BIODEGRADABLE POLYMER AND MOST EFFECTIVE VARIABLES IN PREPARATION OF ESSENTIAL OIL LOADED NANO PARTICLES FOR PULMONARY DELIVERY USING TAGUCHI DESIGN

INDIAN DRUGS ◽

10.53879/id.58.02.12664 ◽

2021 ◽

Vol 58 (02) ◽

pp. 68-75

Author(s):

Avani Khristi ◽

Lalit L. Jha ◽

Abhay Dharamsi ◽

Keyword(s):

Particle Size ◽

Essential Oil ◽

Biodegradable Polymers ◽

Drug Loading ◽

Pulmonary Inflammation ◽

Pulmonary Delivery ◽

Entrapment Efficiency ◽

Nano Particles ◽

Favorable Conditions ◽

Insoluble Polymers

The biodegradability of inhalable nanoparticles (NPs) is an important criterion in prevention of lung toxicity due to NPs which have been taken to cure the condition. Pulmonary inflammation may result due to non-biodegradation or insoluble polymers used to produce NPs. Biodegradable polymers are widely used for manufacturing safe drug-entrapped inhalable NPs for pulmonary delivery. Here in this study, for preparing ajwain essential oil loaded NPs for pulmonary delivery, biodegradable polymers chitosan, gelatin and alginic acid have been evaluated for suitability. Based on the results of trial batches prepared from each polymer, the responses particle size and entrapment efficiency were measured and compared. Out of the three polymers, chitosan was having very good entrapment efficiency, poly dispersive index, drug loading and zeta potential-favorable conditions for pulmonary delivery of essential oils. Further screening of most effective variables in manufacturing nano particles using chitosan, eight batches of nano particles have been prepared as per taguchi orthogonal 2 level array L8 experimental design (Design expert software, version 7.0) where two responses, particle size and entrapment efficiency, have been observed. Based on the results of eight batches, standard effects have been calculated and significant variables identified, for both particle size and entrapment efficiency, for further optimization under design of experiment.

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Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles

Nanotechnology Reviews ◽

10.1515/ntrev-2017-0151 ◽

2017 ◽

Vol 6 (6) ◽

pp. 517-526 ◽

Cited By ~ 3

Author(s):

Permender Rathee ◽

Anjoo Kamboj ◽

Shabir Sidhu

Keyword(s):

Oral Bioavailability ◽

Drug Loading ◽

Average Particle Size ◽

Entrapment Efficiency ◽

Pharmacokinetic Interaction ◽

Precipitation Method ◽

Pharmacokinetic Studies ◽

Average Particle

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.

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Study on the Antibacterial Performance of the Antibacterial Shutter Blades

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.815.333 ◽

2013 ◽

Vol 815 ◽

pp. 333-338

Author(s):

Ming Li Liu ◽

Chun Feng Li ◽

Yun Long Wang ◽

Kai Lu ◽

Jiu Yin Pang ◽

...

Keyword(s):

Antibacterial Agent ◽

Antibacterial Agents ◽

Drug Loading ◽

Antibacterial Properties ◽

Water Soluble ◽

Single Factor ◽

Antibacterial Performance ◽

Loading Amount ◽

Single Factor Experiment ◽

Impregnation Solution

This study used Ag-embedded nanoTiO2, xylan and water-soluble Chitosan as antibacterial agents, respectively prepared shutter blades through the treating solution of the different concentration and the different drug loading amount of the poplar veneer. Through a single factor experiment, this paper analyzes that the different antibacterial agent, concentration of antibacterial agent and the drug loading amount have an effect on the antibacterial properties of the shutter blades. The results show that the order of antibacterial performance of the shutter blades impregnated antibacterial agents is the Ag-embedded nanoTiO2, Chitosan, Xylan. Comprehensiv-ely thought the antibacterial properties and economic index, the optimal concentration of the Ag-embedded nanoTiO2 impregnation solution is 1%.

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FORMULATION, OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES FOR SUSTAINED DRUG DELIVERY USING BOX-BEHNKEN DESIGN

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i1.39932 ◽

2021 ◽

pp. 216-226

Author(s):

GEETHA V. S. ◽

MALARKODI VELRAJ

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Drug Release ◽

Crude Protein ◽

Drug Loading ◽

Entrapment Efficiency ◽

Box Behnken Design ◽

Sustained Drug Delivery ◽

Drug Loading Efficiency

Objective: To formulate, optimize and evaluate 5-fluorouracil loaded liquorice crude protein nanoparticles for sustained drug delivery using Box-Behnken design. Methods: 5-fluorouracil (5-FU) loaded liquorice crude protein (LCP) nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) as stabilizing agent and gluteraldehyde (8% v/v) as cross linking agent. The optimization of prepared nanoparticles was carried out using Box-Behnken design with 3 factors 2 levels and 3 responses. The independent variables were A)5-FU concentration B)LCP concentration and C) sonication time while the responses were R1) Drug entrapment efficiency R2) Drug loading efficiency and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, physicochemical properties like particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, drug loading efficiency and in vitro drug release studies in PBS pH 7.4 (24 h) were carried out. The observed values were found to be in close agreement with the predicted value obtained from the optimization process. Results: 5-fluorouracil loaded LCP nanoparticles were prepared by desolvation method, the optimization was carried out by Box-Behnken design and the final formulation was evaluated for particle size (301.1 nm), zeta-potential (-25.8mV), PDI(0.226), with entrapment efficiency (64.07%), drug loading efficiency (28.54%), in vitro drug release (65.2% in 24 h) respectively. The formulated nanoparticles show Higuchi model drug release kinetics with sustained drug delivery for 24 h in pH7.4 buffer. Conclusion: The results were proved to be the most valuable for the sustained delivery of 5-Fluorouracil using liquorice crude protein as carrier. 5-FU–LCP nanoparticles were prepared using Tween-80 as stabilizing agent and gluteraldehyde as cross-linking agent to possess ideal sustained drug release characteristics.

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FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF AN ANTI-MIGRAINE DRUG

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5.1943 ◽

2018 ◽

Vol 8 (5) ◽

pp. 465-474

Author(s):

S PADMA PRIYA ◽

AN Rajalakshmi ◽

P Ilaveni

Keyword(s):

Drug Release ◽

Sustained Release ◽

Sodium Alginate ◽

Release Kinetics ◽

Drug Loading ◽

Research Work ◽

Entrapment Efficiency ◽

Polyvinyl Pyrrolidone ◽

Anti Migraine Drug

Objective: The objective of this research work is to develop and evaluate mucoadhesive microspheres of an anti-migraine drug for sustained release. Materials and Methods: Mucoadhesive microspheres were prepared by emulsification method using Sodium alginate (SA), polyvinyl pyrrolidone (PVP) and Chitosan in the various drug-polymer ratios of 1:1, 1:2 and 1:3. Nine formulations were formulated and evaluated for possible drug polymer interactions, percentage yield, micromeritic properties, particle size, drug content, drug entrapment efficiency, drug loading, swelling index, In-vitro wash off test, in vitro drug release, surface morphology and release kinetics. Results: The results showed that no significant drug polymer interaction in FTIR studies. Among all the formulations SF3 containing sodium alginate showed 77.18% drug release in 6hrs. Conclusion: Amongst the developed mucoadhesive microspheres, SF3 formulation containing sodium alginate exhibited slow and sustained release in a controlled manner and it is a promising formulation for sustained release of Sumatriptan succinate. Keywords: Mucoadhesive microspheres, Sodium alginate, polyvinyl pyrrolidone, Chitosan, sustained release.

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