Publications by authors named "Manjusha Annaji"

6 Publications

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Resveratrol-loaded nanomedicines for cancer applications.

Cancer Rep (Hoboken) 2021 Mar 2:e1353. Epub 2021 Mar 2.

Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, USA.

Background: Resveratrol (3, 5, 4 -trihydroxystilbene), a natural polyphenol and phytoalexin, has drawn considerable attention in the past decade due to its wide variety of therapeutic activities such as anticancer, anti-inflammatory, and antioxidant properties. However, its poor water solubility, low chemical stability, and short biological half-life limit its clinical utility.

Recent Findings: Nanoparticles overcome the limitations associated with conventional chemotherapeutic drugs, such as limited availability of drugs to the tumor tissues, high systemic exposures, and consequent toxicity to healthy tissues. This review focuses on the physicochemical properties of resveratrol, the therapeutic potential of resveratrol nano-formulations, and the anticancer activity of resveratrol encapsulated nanoparticles on various malignancies such as skin, breast, prostate, colon, liver, ovarian, and lung cancers (focusing on both in vitro and in vivo studies).

Conclusions: Nanotechnology approaches have been extensively utilized to achieve higher solubility, improved oral bioavailability, enhanced stability, and controlled release of resveratrol. The resveratrol nanoparticles have markedly enhanced its anticancer activity both in vitro and in vivo, thus considering it as a potential strategy to fight various cancers.
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http://dx.doi.org/10.1002/cnr2.1353DOI Listing
March 2021

Co-Delivery of Hispolon and Doxorubicin Liposomes Improves Efficacy Against Melanoma Cells.

AAPS PharmSciTech 2020 Nov 4;21(8):304. Epub 2020 Nov 4.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, USA.

Hispolon is a small molecular weight polyphenol that has antioxidant, anti-inflammatory, and anti-proliferative activities. Our recent study has demonstrated hispolon as a potent apoptosis inducer in melanoma cell lines. Doxorubicin is a broad spectrum first-line treatment for various kinds of cancers. In this study, co-delivery of doxorubicin and hispolon using a liposomal system in B16BL6 melanoma cell lines for synergistic cytotoxic effects was investigated. Liposomes were prepared using a lipid film hydration method and loaded with doxorubicin or hispolon. The formulations were characterized for particle size distribution, release profile, and encapsulation efficiency (EE). In addition, in vitro cytotoxicity, in vitro cell apoptosis, and cellular uptake were evaluated. Liposomes exhibited small particle size (mean diameter ~ 100 nm) and narrow size distribution (polydispersity index (< 0.2) and high drug EE% (> 90%). The release from liposomes showed slower release compared to free drug solution as an additional time required for the release of drug from the liposome lipid bilayer. Liposome loaded with doxorubicin or hispolon exhibited significantly higher cytotoxicity against B16BL6 melanoma cells as compared to doxorubicin solution or hispolon solution. Likewise, co-delivery of hispolon and doxorubicin liposomes showed two-fold and three-fold higher cytotoxicity, as compared to hispolon liposomes or doxorubicin liposomes, respectively. In addition, co-delivery of doxorubicin and hispolon in liposomes enhanced apoptosis more than the individual drugs in the liposome formulation. In conclusion, the co-delivery of hispolon and doxorubicin could be a promising therapeutic approach to improve clinical outcomes against melanoma.
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http://dx.doi.org/10.1208/s12249-020-01846-2DOI Listing
November 2020

Application of Extrusion-Based 3D Printed Dosage Forms in the Treatment of Chronic Diseases.

J Pharm Sci 2020 12 6;109(12):3551-3568. Epub 2020 Oct 6.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, AL 36849, USA. Electronic address:

Chronic disease management has been a significant burden in many countries. As most treatment options involve long-term pharmacotherapy, patient compliance has been a challenge, as patients have to remember taking medications on time at the prescribed dose for each disease state. Patients are often required to split the dosage unit, which may lead to under- or over-dose and dose-related adverse effects. However, 3D printing technologies have been used for fabricating personalized medications and multiple drugs in a single dose unit (polypills), which might greatly reduce treatment monitoring, dosing errors, and follow-ups with the health care providers. Extrusion-based 3D printing is the most used technology to fabricate polypills and to customize the dose, dosage form, and release kinetics, which might potentially reduce the risk of patient non-compliance. Although extrusion-based 3D printing has existed for some time, interest in its potential to fabricate dosage forms for treating chronic diseases is still in its infancy. This review focuses on the various extrusion-based 3D printing technologies such as fused deposition modeling, pressure-assisted microsyringe, and direct powder extrusion 3D printing in the preparation of customizable, multi-drug dosage forms for treating chronic diseases.
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http://dx.doi.org/10.1016/j.xphs.2020.09.042DOI Listing
December 2020

Dexamethasone eluting 3D printed metal devices for bone injuries.

Ther Deliv 2020 Jun 1;11(6):373-386. Epub 2020 Jun 1.

Department of Drug Discovery & Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.

Additively manufactured (3D printed), stainless steel implants were coated with dexamethasone using gelatin, chondroitin sulfate for use in bone graft surgeries. The drug and polymers were deposited on the implants with a rough surface using a high precision air brush. The gelatin-chondroitin sulfate layers were cross-linked using glutaraldehyde. The drug content uniformity was within 100 ± 5%, and the thickness of the polymer layer was 410 ± 5.2 μm. The release studies showed a biphasic pattern with an initial burst release followed by slow release up to 3 days. These results are very promising as the slow release implants can be further tested in large animals, such as cattle and horses to prevent the inflammatory cascade following surgeries.
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http://dx.doi.org/10.4155/tde-2020-0014DOI Listing
June 2020

Stability-indicating HPLC method for acyclovir and lidocaine in topical formulations.

Biomed Chromatogr 2020 Mar 12;34(3):e4751. Epub 2020 Jan 12.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

A simple, rapid and accurate stability-indicating HPLC assay was developed for the determination of acyclovir and lidocaine in topical formulations. Chromatographic separation of acyclovir and lidocaine was achieved using a reversed-phase C column and a gradient mobile phase (20 mm ammonium acetate pH 3.5 in water and acetonitrile). The degradation products of acyclovir and lidocaine in the samples were analyzed by ultra performance liquid chromatography-time of flight mass spectrometry. The HPLC method successfully resolved the analytes from the impurities and degradation products in the topical formulation. Furthermore, the method detected the analytes from the human skin leachables following the extraction of the analytes in the skin homogenate samples. The method showed linearity over wide ranges of 5-500 and 10-200 μg/ml for acyclovir and lidocaine in the topical product, respectively, with a correlation coefficient (r ) >0.9995. The relative standard deviations for precision, repeatability, and robustness of the method validation assays were <2%. The skin extraction efficiency for acyclovir and lidocaine was 92.8 ± 0.7% and 91.3 ± 3.2%, respectively, with no interference from the skin leachables. Thus, simultaneous quantification of acyclovir and lidocaine in the topical formulations was achieved.
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http://dx.doi.org/10.1002/bmc.4751DOI Listing
March 2020

Microemulsion and Microporation Effects on the Genistein Permeation Across Dermatomed Human Skin.

AAPS PharmSciTech 2018 Nov 23;19(8):3481-3489. Epub 2018 Aug 23.

Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, 36849, USA.

This study reports the microemulsion (ME) effects on the permeation of genistein across normal (intact) and microporated human skin. The genistein formulation was optimized to know the stable ME region in the pseudo-ternary phase diagrams and to maximize the skin permeation and retention of genistein. The phase diagrams were constructed with different oil phases, surfactants, and their combinations. The influence of formulation factors on the permeation through intact and microporated human skin was determined. Based on its wide ME region, as well as permeation enhancement effects, oleic acid was used as an oil phase with various surfactants and co-surfactants to further maximize the ME region and skin permeation. The water content in the formulation played an important role in the ME stability, droplet size, and flux of genistein. For example, the ME with 20% water exhibited 4- and 9-fold higher flux as compared to the ME base (no water) and aqueous suspension, respectively. Likewise, this formulation had demonstrated 2- and 4-fold higher skin retention as compared to the ME base (no water) and aqueous suspension, respectively. The skin microporation did not significantly increase the skin permeation of genistein from ME formulations. The ME composition, water content, and to a lesser extent the ME particle size played a role in improving the skin permeation and retention of genistein.
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http://dx.doi.org/10.1208/s12249-018-1150-9DOI Listing
November 2018