Encapsulation of Andrographolide in poly(lactide-co-glycolide) Nanoparticles: Formulation Optimization and in vitro Efficacy Studies

Andrographolide is a potential chemopreventive and chemotherapeutic agent that suffers from poor aqueous solubility. Encapsulation in poly(lactide-co-glycolide) (PLGA) nanoparticles can overcome solubility issues and enable sustained release of the drug, resulting in improved therapeutic efficacy. In this study, andrographolide was encapsulated in PLGA nanoparticles via emulsion solvent evaporation technique. Effect of various formulation parameters including polymer composition, polymer molecular weight, polymer to drug ratio, surfactant concentration and the organic solvent used on nanoparticle properties were investigated. A selected formulation was used to determine the effect of encapsulation in nanoparticles on andrographolide’s in vitro anticancer efficacy. Nanoparticles formulated using a polymer with 85:15 lactide to glycolide ratio and ethyl acetate as the organic solvent were found to be optimal based on average hydrodynamic particle size (135 ± 4 nm) and drug loading (2.6 ± 0.6%w/w). This formulation demonstrated sustained release of andrographolide over 48 h and demonstrated significantly greater in vitro anticancer efficacy compared to free drug in a metastatic breast cancer cell line. These results suggest that additional, more in-depth efficacy studies are warranted for the nanoparticle formulation of andrographolide.

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Preparation and evaluation of a stable and sustained release of lansoprazole-loaded poly(d,l-lactide-co-glycolide) polymeric nanoparticles

Journal of Polymer Engineering ◽

10.1515/polyeng-2019-0164 ◽

2019 ◽

Vol 39 (9) ◽

pp. 822-829 ◽

Cited By ~ 1

Author(s):

Bader B. Alsulays ◽

Md. Khalid Anwer ◽

Mohammed F. Aldawsari ◽

Alhussain Aodah ◽

Elsadig Adam ◽

...

Keyword(s):

Sustained Release ◽

Magnesium Oxide ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Plga Nanoparticles ◽

Base Peak ◽

Solvent Evaporation Method ◽

Physicochemical Stability ◽

Preparation And Evaluation

Abstract The aim of the study was to prepare lansoprazole (LNS)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles in order to improve the physicochemical stability associated with LNS. We synthesized LNS-loaded PLGA nanoparticles in the presence of magnesium oxide as alkalizer to improve the release of LNS and stability against photodegradation. The LNS-encapsulated PLGA nanoparticles were developed by the nanoprecipitation/solvent evaporation method, resulting in a particle size of 246.7 ± 3.4 nm, polydispersity index (PDI) of 0.126, percent drug entrapment (PDE) of 82.85 ± 4.5%, percent drug loading (PDL) of 3.54 ± 0.34%, and pH of 8.10 ± 0.56. The developed nanoparticles were further evaluated for in vitro release and resistance to photodegradation by NMR spectroscopy and LC-MS. The sustained release of the drug was confirmed after the encapsulation of LNS in the PLGA matrix. The protection of LNS in the PLGA matrix against photodegradation was confirmed by NMR and LC-MS studies. The LC-MS of UV-exposed samples of pure LNS and LNS-loaded PLGA nanoparticles at 254 nm showed the same (M + 1) peak at 370 m/e, and the base peak at 369 m/e accounted for the unchanged structure of LNS inside PLGA nanoparticles. Overall, it was proved that PLGA nanoparticles in the presence of magnesium oxide are an efficient carrier to deliver and protect LNS from physicochemical instability.

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Preparation, evaluation, and in vitro release of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules

Technology and Health Care ◽

10.3233/thc-202529 ◽

2020 ◽

pp. 1-9

Author(s):

Yunhong Wang ◽

Rong Hu ◽

Yanlei Guo ◽

Weihan Qin ◽

Xiaomei Zhang ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Release Rate ◽

Orthogonal Design ◽

Drug Loading ◽

In Vitro Release ◽

Core Material ◽

Evaluation Indexes ◽

Vitro Release

OBJECTIVE: In this study we explore the method to prepare tanshinone self-microemulsifying sustained-release microcapsules using tanshinone self-microemulsion as the core material, and chitosan and alginate as capsule materials. METHODS: The optimal preparation technology of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules was determined by using the orthogonal design experiment and single-factor analysis. The drug loading and entrapment rate were used as evaluation indexes to assess the quality of the drug, and the in vitro release rate was used to evaluate the drug release performance. RESULTS: The best technology of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules is as follows: the concentration of alginate is 1.5%, the ratio of tanshinone self-microemulsion volume to alginate volume to chitosan mass is 1:1:0.5 (ml: ml: g), and the best concentration of calcium chloride is 2.0%. To prepare the microcapsules using this technology, the drug loading will be 0.046%, the entrapment rate will be 80.23%, and the 24-hour in vitro cumulative release rate will be 97.4%. CONCLUSION: The release of the microcapsules conforms to the Higuchi equation and the first-order drug release model and has a good sustained-release performance.

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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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Photodynamic Treatment of Colorectal Cancer Using Chlorin e6-Loaded Poly(lactide-co-glycolide)- Based Nanoparticles

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3170 ◽

2021 ◽

Vol 17 (10) ◽

pp. 1939-1950

Author(s):

Beibei Lin ◽

Xuegu Xu ◽

Xiaobi Zhang ◽

Yinfei Yu ◽

Xiaoling Wang

Keyword(s):

Colorectal Cancer ◽

Drug Loading ◽

Average Diameter ◽

Plga Nanoparticles ◽

Chlorin E6 ◽

Photodynamic Treatment ◽

Hct 116 ◽

Hct 116 Cells ◽

The Stability

We prepared poly(lactide-co-glycolide) (PLGA) encapsulated with chlorin e6 (Ce6) in an effort to increase the stability and efficiency of photosensitizers for photodynamic therapy (PDT). We determined that Ce6-loaded PLGA nanoparticles (PLGA-Ce6 NPs) had drug-loading efficiency of 5%. The efficiency of encapsulation was 82%, the zeta potential was- 25 mV, and the average diameter was 130 nm. The encapsulation of Ce6 in PLGA nanoparticles showed excellent stability. The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced uptake of the nanoparticles. An in vitro anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC50 value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs penetrated more profoundly and had better phototoxicity than pure drugs. These findings suggest that PLGA-Ce6 NPs might serve as PDT for colorectal cancer.

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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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PLGA Nanoparticles for Oral Delivery of Hydrophobic Drugs: Influence of Organic Solvent on Nanoparticle Formation and Release Behavior In Vitro and In Vivo Using Estradiol as a Model Drug

Journal of Pharmaceutical Sciences ◽

10.1002/jps.21158 ◽

2008 ◽

Vol 97 (4) ◽

pp. 1530-1542 ◽

Cited By ~ 161

Author(s):

D.K. Sahana ◽

G. Mittal ◽

V. Bhardwaj ◽

M.N.V.Ravi Kumar

Keyword(s):

Organic Solvent ◽

Oral Delivery ◽

Plga Nanoparticles ◽

Hydrophobic Drugs ◽

Release Behavior ◽

Nanoparticle Formation ◽

Model Drug

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HYALURONIC ACID-DOCETAXEL CONJUGATE LOADED NANOLIPOSOMES FOR TARGETING TUMOR CELLS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i6.39026 ◽

2020 ◽

pp. 88-99

Author(s):

MULUNEH FROMSA SEIFU ◽

LILA KANTA NATH ◽

DEBASHIS DUTTA

Keyword(s):

Hyaluronic Acid ◽

Glial Cells ◽

Cellular Uptake ◽

Drug Loading ◽

Microscopic Investigation ◽

In Vitro Cytotoxicity ◽

Scanning Calorimetry ◽

Anticancer Efficacy ◽

Apoptotic Effect

Objective: Docetaxel (DTX), a potent anticancer drug, is suffering from non-specificity and drug resistance as major limitations. In this investigation, we developed Hyaluronic acid (HA)-Docetaxel conjugate (HA-DTX) loaded nanoliposomes to target cancer cells via passive and active targeting approaches. Methods: HA-DTX was synthesized and characterized by UV-Visible spectrophotometry, FT-IR spectroscopy, 1H NMR spectroscopy, Differential scanning calorimetry and X-ray diffraction and then loaded into nanoliposomes (L-NLs) by thin-film hydration method. L-NLs were characterized physicochemically and evaluated for anticancer efficacy by in vitro cytotoxicity study in glioma cells (C6 glial cells); cellular uptake and apoptotic effect were investigated by fluorescence microscopy. Results: HA-DTX was successfully synthesized; L-NLs had an average size of 123.0±16.53 nm, polydispersity index of 0.246±0.01 and zeta potential of 44.4±6.79 mV. Also, L-NLs exhibited 90.54%±4.22 of drug loading efficiency and 2.68%±0.12 of drug loading, releasing about 57.72%±1.17 at pH 5.2 and only 14.14%±1.32 at pH 7.4 after 48 h. No significant change instability was observed after storage at 5 °C±3 °C as well as at 25 °C±2 °C/60% RH±5% RH for 6 mo. The cytotoxicity effect of L-NLs was higher by 10% that of marketed formulation at 10 µg/ml docetaxel concentration. Fluorescence microscopic investigation showed that more cellular uptake and apoptotic effect were observed in L-NLs treated C6 glial cells than in those treated with the marketed formulation. Conclusion: HA-DTX loaded nanoliposomes enabled docetaxel to target C6 glial cells with better efficacy and might be effective to treat glioma.

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BIODEGRADABLE POLYMER: A NOVEL PHARMACEUTICAL CARRIER FOR SUSTAINED RELEASE OF METRONIDAZOLE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i10.19903 ◽

2017 ◽

Vol 10 (10) ◽

pp. 136

Author(s):

Gayathri Hariharan ◽

Priyanka Sinha

Keyword(s):

Particle Size ◽

Drug Release ◽

Sustained Release ◽

Biodegradable Polymer ◽

Drug Loading ◽

Cross Linking ◽

Loading Capacity ◽

Flow Properties ◽

Chitosan Microspheres

Objective: To optimize and evaluate the formulation of metronidazole (MT)-loaded chitosan microspheres and to investigate the efficiency of biodegradable polymer in developing sustained release formulation of MT to prolong the action of drug.Methods: MT microspheres were prepared using emulsion cross-linking method. Polymer-drug compatibility study was done using Fourier transform infrared. Physical characteristics were evaluated by particle size,SEM, flow properties etc. In vitro studies for evaluating drug release for MT-loaded chitosan microspheres were done by dissolution study.Results: Particle size of the formulated microspheres was found to be within the range of 110-130 μm. Flow properties of F1-F7 such as angle of repose, bulk density, and tapped density were found to be within limits. Drug entrapment efficiency was found to be better for all the formulations within the range of 74.82-84.32% w/w. Drug loading capacity was found to be in the range of 56-83.2% w/v. In vitro drug release was found to be in the range of 81.32-96.23% w/v.Conclusion: In spite of all the above results, we conclude that F5 formulation was optimized depending on the data obtained from the drug loading capacity and percentage drug release studies. F5 formulation is formulated with drug-polymer ratio 1:2 with 1% of di octyl sodium sulfo succinate and 8 ml of glutaraldehyde as a cross-linking agent.

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Thermosensitive Chitosan Hydrogels Containing Polymeric Microspheres for Vaginal Drug Delivery

BioMed Research International ◽

10.1155/2017/3564060 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Ting-Ting Yang ◽

Yuan-Zheng Cheng ◽

Meng Qin ◽

Yong-Hong Wang ◽

Hong-Li Yu ◽

...

Keyword(s):

Drug Delivery ◽

Sustained Release ◽

Delivery System ◽

Drug Loading ◽

Great Promise ◽

Burst Release ◽

Bletilla Striata ◽

Vaginal Drug Delivery ◽

Thermosensitive Hydrogels

Thermosensitive hydrogels have increasingly received considerable attention for local drug delivery based on many advantages. However, burst release of drugs is becoming a critical challenge when the hydrogels are employed. Microspheres- (MS-) loaded thermosensitive hydrogels were thus fabricated to address this limitation. Employing an orthogonal design, the spray-dried operations of tenofovir (TFV)/Bletilla striata polysaccharide (BSP)/chitosan (CTS) MS were optimized according to the drug loading (DL). The physicochemical properties of the optimal MS (MS F) were characterized. Depending on the gelation temperature and gelating time, the optimal CTS-sodium alginate- (SA-) α,β-glycerophosphate (GP) (CTS-SA-GP) hydrogel was obtained. Observed by scanning electron microscope (SEM), TFV/BSP/CTS MS were successfully encapsulated in CTS-SA-GP. In vitro releasing demonstrated that MS F-CTS-SA-GP retained desirable in vitro sustained-release characteristics as a vaginal delivery system. Bioadhesion measurement showed that MS-CTS-SA-GP exhibited the highest mucoadhesive strength. Collectively, MS-CTS-SA-GP holds great promise for topical applications as a sustained-release vaginal drug delivery system.

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