Development and In Vitro Evaluation of a Zerumbone Loaded Nanosuspension Drug Delivery System

Zerumbone extracted from the volatile oil of rhizomes available from the Zinigiber zerumbet has promising pharmacological activity. However, it has poor aqueous solubility and dissolution characteristics. To improve this, a nanosuspension formulation of zerumbone was developed. Nanosuspensions were formulated using high-pressure homogenization (HPH) with sodium dodecyl sulphate (SDS) and hydroxypropylmethylcellulose (HPMC) as stabilizers; the formulation was optimized and freeze dried. The optimized nanosuspension product was evaluated using an optical light microscope, photon correlation spectroscopy (PCS), polydispersity index, zeta potential, SEM, differential scanning calorimetry (DSC) and FT-IR. The physical stability of the nanosuspensions was evaluated for 30 days at 4 °C, 25 °C, and 37 °C. To validate the theoretical benefit of the increased surface area, we determined an in vitro saturation solubility and dissolution profile. The mean particle size, polydispersity index and zeta potential of the zerumbone nanosuspensions stabilized by SDS versus HPMC were found to be 211 ± 27 nm vs. 398 ± 3.5 nm, 0.39 ± 0.06 vs. 0.55 ± 0.004, and −30.86 ± 2.3 mV vs. −3.37 ± 0.002 mV, respectively. The in vitro saturation solubility and dissolution revealed improved solubility for the zerumbone nanosuspension. These results suggested that the nanosuspensionlization improves the saturation solubility and dissolution profile of zerumbone, which may facilitate its use as a therapeutic agent in the future.

Download Full-text

Quality by Design Optimization of Cold Sonochemical Synthesis of Zidovudine-Lamivudine Nanosuspensions

Pharmaceutics ◽

10.3390/pharmaceutics12040367 ◽

2020 ◽

Vol 12 (4) ◽

pp. 367 ◽

Cited By ~ 6

Author(s):

Bwalya A. Witika ◽

Vincent J. Smith ◽

Roderick B. Walker

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Sodium Dodecyl ◽

In Vitro Cytotoxicity ◽

Polydispersity Index ◽

Glycol Succinate ◽

Scanning Calorimetry ◽

X Ray ◽

Cytotoxicity Studies

Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used to manage HIV/AIDS infection. The compounds require frequent dosing, exhibit unpredictable bioavailability and a side effect profile that includes hepato- and haema-toxicity. A novel pseudo one-solvent bottom-up approach and Design of Experiments using sodium dodecyl sulphate (SDS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) to electrosterically stablize the nano co-crystals was used to develop, produce and optimize 3TC and AZT nano co-crystals. Equimolar solutions of 3TC in surfactant dissolved in de-ionised water and AZT in methanol were rapidly injected into a vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer and the particle size, polydispersity index and Zeta potential determined. Optimization of the nanosuspensions was conducted using a Central Composite Design to produce nano co-crystals with specific identified and desirable Critical Quality Attributes including particle size (PS) < 1000 nm, polydispersity index (PDI) < 0.500 and Zeta potential (ZP) < −30mV. Further characterization was undertaken using Fourier Transform infrared spectroscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry, powder X-ray diffraction and transmission electron microscopy. In vitro cytotoxicity studies revealed that the optimized nano co-crystals reduced the toxicity of AZT and 3TC to HeLa cells.

Download Full-text

A Comparative Study of the Effect of Different Stabilizers on the Critical Quality Attributes of Self-Assembling Nano Co-Crystals

Pharmaceutics ◽

10.3390/pharmaceutics12020182 ◽

2020 ◽

Vol 12 (2) ◽

pp. 182 ◽

Cited By ~ 4

Author(s):

Bwalya A. Witika ◽

Vincent J. Smith ◽

Roderick B. Walker

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Antiviral Agents ◽

Sodium Dodecyl ◽

Quality Attributes ◽

Polydispersity Index ◽

Scanning Calorimetry ◽

Critical Quality Attributes ◽

X Ray ◽

Self Assembling

Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used orally to manage HIV/AIDS infection. A pseudo one-solvent bottom-up approach was used to develop and produce nano co-crystals of 3TC and AZT. Equimolar amounts of 3TC dissolved in de-ionized water and AZT in methanol were rapidly injected into a pre-cooled vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer. The particle size, polydispersity index and Zeta potential were elucidated. Further characterization was undertaken using powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and energy dispersive X-ray spectroscopy scanning electron microscopy. Different surfactants were assessed for their ability to stabilize the nano co-crystals and for their ability to produce nano co-crystals with specific and desirable critical quality attributes (CQA) including particle size (PS) < 1000 nm, polydispersity index (PDI) < 0.500 and Zeta potential (ZP) < −30 mV. All surfactants produced co-crystals in the nanometer range. The PDI and PS are concentration-dependent for all nano co-crystals manufactured while only ZP was within specification when sodium dodecyl sulfate was used in the process.

Download Full-text

FORMULATION, OPTIMIZATION, AND IN VITRO EVALUATION OF POLYMERIC NANOSUSPENSION OF FLURBIPROFEN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i11.35670 ◽

2019 ◽

pp. 183-191

Author(s):

PANKAJ JADHAV ◽

ADHIKRAO YADAV

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Hydroxypropyl Methylcellulose ◽

Entrapment Efficiency ◽

Aqueous Solubility ◽

Water Soluble ◽

Dissolution Profile ◽

Scanning Calorimetry ◽

Transmission Electron

Objective: At present, more than 40% of drugs are poorly water-soluble that leads to reduced bioavailability. The objective of the present investigation was to overcome the issue of poor aqueous solubility of drug; therefore, stable flurbiprofen (FBF) nanosuspensions were developed by nanoprecipitation method. Materials and Methods: Based on particle size, zeta potential, and entrapment efficiency, the polymeric system of hydroxypropyl methylcellulose E15 and poloxamer 188 was used effectively. The prepared formulations were evaluated for Fourier transform infrared spectroscopy, transmission electron microscopy, differential scanning calorimetry, powder X-ray diffraction, saturation solubility, entrapment efficiency, particle size, zeta potential, dissolution profile, and stability. Results: The resultant FBF nanosuspensions depicted particles in size range of 200–400 nm and were physically stable. After nanonization, the crystallinity of FBF was slightly reduced in the presence of excipients. The aqueous solubility and dissolution rate of all FBF nanosuspensions were significantly increased as compared with FBF powder. Conclusion: This investigation demonstrated that nanoprecipitation is a promising method to develop stable polymeric nanosuspension of FBF with significant increase in its aqueous solubility.

Download Full-text

Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet

Molecules ◽

10.3390/molecules26051485 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1485

Author(s):

Yogeeta O. Agrawal ◽

Umesh B. Mahajan ◽

Vinit V. Agnihotri ◽

Mayur S. Nilange ◽

Hitendra S. Mahajan ◽

...

Keyword(s):

Particle Size ◽

Zeta Potential ◽

High Fat Diet ◽

Entrapment Efficiency ◽

Polydispersity Index ◽

Nanostructured Lipid Carrier ◽

High Fat ◽

Scanning Calorimetry ◽

Bioavailability Enhancement

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of −28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.

Download Full-text

Formulation and Evaluation of Lamivudine Nanosuspension

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i4-s.4961 ◽

2021 ◽

Vol 11 (4-S) ◽

pp. 71-77

Author(s):

Yerikala Ramesh ◽

Ballem Sarayu ◽

Guduru Hari Chandana ◽

Obili Neelima ◽

Shaik Sana

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Polydispersity Index ◽

Stability Studies ◽

N Value ◽

Saturation Solubility ◽

Drug Content ◽

Distribution Ranges ◽

Evaluation Parameters

The present research aimed to develop & Evaluation of Lamivudine Nanosuspension. Lamivudine is a potent in vitro inhibitor of human immune deficiency virus belongs to the category of anti-retroviral drugs. The formulated Nanosuspension was subjected to various evaluation parameters like particle size, polydispersity index, zeta potential, drug content, viscosity, saturation solubility studies, In vitro release, treatment of kinetic data, and stability studies. The polydispersity ranged from 0.218 PDI to 0.331 PDI and zeta potential ranged from -1.60 mV to -4.79 mV are the important evaluation parameters are responsible for the stability of nanosuspensions. The Polydispersity index presents the quantity of particle size distribution ranges from 452.4 nm to 532.2 nm. In this result, LNSF4 shows spectacular drug content range of 86±1.8% to 97±2.5% it is the maximum drug content. The Brook field viscometer to determine the viscosity of Lamivudine Nano suspension of different formulations was found to be 44.4±2.1 cps to 87.7±1.4 cps. The general Nanosuspension formulations LNSF4 shows 98.64 % better controlled released in comparison with abundant formulation. In all the cases the best-fit model encounter uoto be peppas with ‘n’ value between 0.768 to 0.917. The ‘n’ value of formulation LNSF4 was 0.876 and suggesting so the drug was released by Zero-order kinetics. Acceleration stability studies intermediate storage condition has been changed from 30°C ± 2°C and 60% RH ± 5% Relative Humidity. After a 90 days study it revolves that there’s no change in Drug content, In vitro drug release, and particle size. Keywords: Lamivudine, Nanosuspension, Saturation solubility, Scanning Electron Microscopy, Stability study.

Download Full-text

Cyclodextrins-in-Liposomes: A Promising Delivery System for Lippia sidoides and Syzygium aromaticum Essential Oils

Life ◽

10.3390/life12010095 ◽

2022 ◽

Vol 12 (1) ◽

pp. 95

Author(s):

Iara Baldim ◽

Andressa M. Oliveira ◽

Eliana B. Souto ◽

Wanderley P. Oliveira

Keyword(s):

Zeta Potential ◽

Essential Oils ◽

Physical Stability ◽

Study Drug ◽

Syzygium Aromaticum ◽

Scanning Calorimetry ◽

Ethanol Injection ◽

Lippia Sidoides ◽

Freeze Dried ◽

Mean Size

Biological activity of essential oils (EOs) has been extensively reported; however, their low aqueous solubility, high photosensitivity, and volatility compromise a broad industrial use of these compounds. To overcome these limitations, we proposed a nanoencapsulation approach to protect EOs, that aims to increase their stability and modulate their release profile. In this study, drug-in-cyclodextrin-in-liposomes encapsulating two essential oils (Lippia sidoides and Syzygium aromaticum) and their respective major compounds (thymol and eugenol) were produced by ethanol injection and freeze-dried to form proliposomes and further physicochemically characterized. Liposomes showed high physical stability over one month of storage at 4 °C, with slight changes in the mean size, polydispersity index (PDI), and zeta potential. Reconstituted proliposomes showed a mean size between 350 and 3300 nm, PDI from 0.29 to 0.41, and zeta potential between −22 and −26 mV. Differential scanning calorimetry and X-ray diffraction of proliposomes revealed a less-ordered crystalline structure, leading to high retention of the major bioactive compounds (between 73% and 93% for eugenol, and 74% and 84% for thymol). This work highlights the advantages of using drug-in-cyclodextrin-in-liposomes as delivery systems to retain volatile compounds, increasing their physicochemical stability and their promising potential to be utilized as carriers in products in the pharmaceutical, food, and cosmetic industries.

Download Full-text

Preparation and characterization of liposomes double loaded with amphotericin B and amphotericin B/hydroxypropyl-beta-cyclodextrin inclusion complex

Pharmaceutical Nanotechnology ◽

10.2174/2211738509666210310160436 ◽

2021 ◽

Vol 09 ◽

Author(s):

Thi Hai Yen Tran ◽

Thi Thu Giang Vu ◽

Thi Minh Hue Pham

Keyword(s):

Zeta Potential ◽

Inclusion Complex ◽

Amphotericin B ◽

Water Soluble ◽

Polydispersity Index ◽

Phospholipid Bilayer ◽

Loading Capacity ◽

Scanning Calorimetry ◽

Aqueous Core

Background: Amphotericin B (AMB) is water-insoluble polyene, which has a broad spectrum of antifungal activity. The hydrophobic drug only exits in the phospholipid bilayer, leading to a low-drug liposomal loading capacity. Objectives: This study is designed to prepare water-soluble inclusion complex (IC) between AMB and cyclodextrin (CD) to formulate liposomal vesicles, double-loaded with drug molecules in the phospholipid bilayer and AMB/CD IC in the aqueous core. Methods: Water-soluble AMB/CD IC was prepared by pH adjustment of the aqueous media and consequently characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Liposomes double-loaded with AMB were formulated by the thin-film hydration method and accordingly evaluated for vesicle size, polydispersity index, entrapment efficiency, zeta potential and in vitro drug leakage. Results: Hydroxypropyl β cyclodextrin (HP-β-CD) better solubilized AMB than both α-CD and β-CD e.g, the concentration of water-soluble AMB/HP-β-CD IC could reach 465 µg/mL. Both DSC and SEM data illustrated that the drug no longer existed in its crystalline form, a in AMB/HP-β-CD IC. Liposomes double-loaded with hydrophilic AMB/HP-β-CD IC and hydrophobic AMB had a diameter of 270 nm, polydispersity index less than 0.27 and zeta potential ca. – 42.8 mV. Moreover, liposomes double loaded with AMB enhanced drug-liposomal loading capacity by 25%, less leaked drug in phosphate buffer pH 7.4 at 37oC in comparison to liposomes loaded with only hydrophobic AMB. Conclusion: Liposomes double loaded with AMB and AMB/HP-β-CD IC increased drug-encapsulation ability and in vitro stability, suggesting potential drug delivery systems.

Download Full-text

Production and Characterization of Chitosan–Polyanion Nanoparticles by Polyelectrolyte Complexation Assisted by High-Intensity Sonication for the Modified Release of Methotrexate

Pharmaceuticals ◽

10.3390/ph13010011 ◽

2020 ◽

Vol 13 (1) ◽

pp. 11 ◽

Cited By ~ 3

Author(s):

Yhors Ciro ◽

John Rojas ◽

Maria Alhajj ◽

Gustavo Carabali ◽

Constain Salamanca

Keyword(s):

Zeta Potential ◽

Maleic Acid ◽

High Intensity ◽

Physical Stability ◽

Release Mechanism ◽

Diffusion Controlled ◽

Polyelectrolyte Complexation ◽

Anticancer Treatment ◽

Particle Parameters

A promising strategy to improve the effectivity of anticancer treatment and decrease its side effects is to modulate drug release by using nanoparticulates (NPs) as carriers. In this study, methotrexate-loaded chitosan–polyanion nanoparticles were produced by polyelectrolyte complexation assisted by high-intensity sonication, using several anionic polymers, such as the sodium and potassium salts of poly(maleic acid-alt-ethylene) and poly(maleic acid-alt-octadecene), here named PAM-2 and PAM-18, respectively. Such NPs were analyzed and characterized according to particle size, polydispersity index, zeta potential and encapsulation efficiency. Likewise, their physical stability was tested at 4 °C and 40 °C in order to evaluate any change in the previously mentioned particle parameters. The in vitro methotrexate release was assessed at a pH of 7.4, which simulated physiological conditions, and the data were fitted to the heuristic models of order one, Higuchi, Peppas–Sahlin and Korsmeyer–Peppas. The results revealed that most of the MTX-chitosan–polyanion NPs have positive zeta potential values, sizes <280 nm and monodisperse populations, except for the NPs formed with PAM-18 polyanions. Further, the NPs showed adequate physical stability, preventing NP–NP aggregation. Likewise, these carriers modified the MTX release by an anomalous mechanism, where the NPs formed with PAM-2 polymer led to a release mechanism controlled by diffusion and relaxation, whereas the NPs formed with PAM-18 led to a mainly diffusion-controlled release mechanism.

Download Full-text

Chitosan nanoparticles for tamoxifen delivery and cytotoxicity to MCF-7 and Vero cells

Pure and Applied Chemistry ◽

10.1351/pac-con-11-01-06 ◽

2011 ◽

Vol 83 (11) ◽

pp. 2027-2040 ◽

Cited By ~ 12

Author(s):

Neralakere Ramanna Ravikumara ◽

Basavaraj Madhusudhan

Keyword(s):

Particle Size ◽

Chitosan Nanoparticles ◽

Vero Cells ◽

In Vitro Cytotoxicity ◽

Correlation Spectroscopy ◽

Scanning Calorimetry ◽

Ζ Potential ◽

Human Red Blood Cells ◽

Tamoxifen Citrate

In this study, tamoxifen citrate-loaded chitosan nanoparticles (tamoxcL-ChtNPs) and tamoxifen citrate-free chitosan nanoparticles (tamoxcF-ChtNPs) were prepared by an ionic gelation (IG) method. The physicochemical properties of the nanoparticles were analyzed for particle size, zeta (ζ) potential, and other characteristics using photon correlation spectroscopy (PCS), zeta phase analysis light scattering (PALS), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and differential scanning calorimetry (DSC). The variation in particle size was assessed by changing the concentration of chitosan, pentasodium tripolyphosphate (TPP), and the pH of the solution. The optimized tamoxcL-ChtNPs showed mean diameter of 187 nm, polydispersity of 0.125, and ζ-potential of +19.1 mV. The encapsulation efficiency (EE) of tamoxifen citrate (tamoxc) increased at higher concentrations, and release of tamoxc from the chitosan matrix displayed controlled biphasic behavior. Those tamoxcL-ChtNPs tested for chemosensitivity showed dose- and time-dependent antiproliferative activity of tamoxc. Further, tamoxcL-ChtNPs were found to be hemocompatible with human red blood cells (RBCs) and safe by in vitro cytotoxicity tests, suggesting that they offer promise as drug delivery systems in therapy.

Download Full-text

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

Pharmaceutics ◽

10.3390/pharmaceutics14010129 ◽

2022 ◽

Vol 14 (1) ◽

pp. 129

Author(s):

Hassan Shah ◽

Asadullah Madni ◽

Muhammad Muzamil Khan ◽

Fiaz-ud-Din Ahmad ◽

Nasrullah Jan ◽

...

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Release Rate ◽

In Vitro Release ◽

Chemotherapeutic Agents ◽

Ph Responsive ◽

Scanning Calorimetry ◽

Cholesteryl Hemisuccinate ◽

Vitro Release

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08–206.4 ± 2.26 nm, zeta potential was −17.8 ± 1.26 to −24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

Download Full-text