Research

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20 pages, 3666 KiB

Open AccessArticle

Development and Preclinical Investigation of Physically Cross-Linked and pH-Sensitive Polymeric Gels as Potential Vaginal Contraceptives

by Ankit Rochani, Vivek Agrahari, Neelima Chandra, Onkar N. Singh, Timothy J. McCormick, Gustavo F. Doncel, Meredith R. Clark and Gagan Kaushal

Polymers 2022, 14(9), 1728; https://doi.org/10.3390/polym14091728 - 23 Apr 2022

Cited by 5 | Viewed by 1984

Abstract

This study explored the development of cross-linked gels to potentially provide a physical barrier to vaginal sperm transport for contraception. Two types of gels were formulated, a physically cross-linked iota-carrageenan (C_i) phenylboronic acid functionalized hydroxylpropylmethyacrylate copolymer (PBA)-based (C_i-PBA) gel, [...] Read more.

This study explored the development of cross-linked gels to potentially provide a physical barrier to vaginal sperm transport for contraception. Two types of gels were formulated, a physically cross-linked iota-carrageenan (C_i) phenylboronic acid functionalized hydroxylpropylmethyacrylate copolymer (PBA)-based (C_i-PBA) gel, designed to block vaginal sperm transport. The second gel was pH-shifting cross-linked C_i-polyvinyl alcohol-boric acid (C_i-PVA-BA) gel, designed to modulate its properties in forming a viscoelastic, weakly cross-linked transient network (due to C_i gelling properties) on vaginal application (at acidic pH of ~3.5–4.5) to a more elastic, densely cross-linked (due to borate-diol cross-linking) gel network at basic pH of 7–8 of seminal fluid, thereby acting as a physical barrier to motile sperm. The gels were characterized for dynamic rheology, physicochemical properties, and impact on sperm functionality (motility, viability, penetration). The rheology data confirmed that the C_i-PBA gel was formed by ionic interactions whereas C_i-PVA-BA gel was chemically cross-linked and became more elastic at basic pH. Based on the screening data, lead gels were selected for in vitro sperm functionality testing. The in vitro results confirmed that the C_i-PBA and C_i-PVA-BA gels created a barrier at the sperm-gel interface, providing sperm blocking properties. For preclinical proof-of-concept, the C_i-PBA gels were applied vaginally and tested for contraceptive efficacy in rabbits, demonstrating only partial efficacy (40–60%). Overall, the in vitro and in vivo results support the development and further optimization of cross-linked gels using commercially available materials as vaginal contraceptives. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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17 pages, 4608 KiB

Open AccessArticle

Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen

by Raj Patel, Quezia Lacerda, Brian E. Oeffinger, John R. Eisenbrey, Ankit K. Rochani, Gagan Kaushal, Corinne E. Wessner and Margaret A. Wheatley

Polymers 2022, 14(8), 1568; https://doi.org/10.3390/polym14081568 - 12 Apr 2022

Cited by 3 | Viewed by 1773

Abstract

Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an [...] Read more.

Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 10⁹ microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses calculated for head and neck squamous cell carcinoma, the cancer of choice. Interestingly, paclitaxel encapsulation efficiency increased from 1.66% to 3.48% when lonidamine was included. During preparation, the combination of single drug-loaded micelles gave higher encapsulation (µg drug/g microbubbles) than micelles loaded with either drug alone (lonidamine, 104.85 ± 22.87 vs. 87.54 ± 16.41), paclitaxel (187.35 ± 8.38 vs. 136.51 ± 30.66). In vivo intravenous microbubbles produced prompt ultrasound enhancement within tumors lasting 3–5 min, indicating penetration into tumor vasculature. The ability to locally destroy the microbubble within the tumor vasculature was confirmed using a series of higher intensity ultrasound pulses. This ability to locally destroy microbubbles shows therapeutic promise that warrants further investigation. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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17 pages, 4483 KiB

Open AccessEditor’s ChoiceArticle

Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention

by Xin Tong, Sravan Kumar Patel, Jing Li, Dorothy Patton, Elaine Xu, Peter L. Anderson, Urvi Parikh, Yvonne Sweeney, Julie Strizki, Sharon L. Hillier and Lisa C. Rohan

Polymers 2022, 14(6), 1196; https://doi.org/10.3390/polym14061196 - 16 Mar 2022

Cited by 2 | Viewed by 2213

Abstract

MK-2048 is a second-generation integrase inhibitor active against HIV, which has been applied vaginally using ring formulations. In this work, a nanoparticle-in-film technology was developed as a discrete pre-exposure prophylactic product option against HIV for an extended duration of use. A film platform [...] Read more.

MK-2048 is a second-generation integrase inhibitor active against HIV, which has been applied vaginally using ring formulations. In this work, a nanoparticle-in-film technology was developed as a discrete pre-exposure prophylactic product option against HIV for an extended duration of use. A film platform loaded with poly (lactic-co-glycolic acid) nanoparticles (PNP) encapsulating MK-2048 was engineered. MK-2048 PNPs were loaded into films that were manufactured via the solvent casting method. Physicochemical and mechanical properties, in vitro efficacy, Lactobacillus compatibility, in vitro and ex vivo permeability, and in vivo pharmacokinetics in macaques were evaluated. PNPs with a mean diameter of 382.2 nm and −15.2 mV zeta potential were obtained with 95.2% drug encapsulation efficiency. PNP films showed comparable in vitro efficacy to free MK-2048 (IC₅₀ 0.46 vs. 0.54 nM) and were found to have no impact on Lactobacillus. MK-2048 encapsulated in PNPs showed an increase in permeability (>4-fold) compared to the free MK-2048 in MDCKII cell lines. Furthermore, PNPs had higher ectocervical tissue permeability (1.7-fold) compared to free MK-2048. PNP films showed sustained drug levels for at least 3 weeks in the macaque vaginal fluid. This work demonstrates the synergy of integrating nanomedicine and polymeric film technology to achieve sustained vaginal drug delivery. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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16 pages, 3108 KiB

Open AccessArticle

Self-Assembly of Soluble Chitosan Derivatives Nanoparticles for Vaccine: Synthesis, Characterization and Evaluation

by Jinbao Liu, Shuang Yu, Wanying Qu, Zheng Jin and Kai Zhao

Polymers 2021, 13(23), 4097; https://doi.org/10.3390/polym13234097 - 25 Nov 2021

Cited by 4 | Viewed by 1564

Abstract

Herein, a novel chitosan derivative nanoparticle was proposed to function as a delivery carrier. First of all, an improvement was made to the way N-2-hydroxypropyl trimcthyl ammonium chloride chitosan (N-2-HACC) was synthesized. Moreover, the solution to one-step synthesis of N-2-HACC from chitosan (CS) [...] Read more.

Herein, a novel chitosan derivative nanoparticle was proposed to function as a delivery carrier. First of all, an improvement was made to the way N-2-hydroxypropyl trimcthyl ammonium chloride chitosan (N-2-HACC) was synthesized. Moreover, the solution to one-step synthesis of N-2-HACC from chitosan (CS) was developed. Different from the previous report, the synthesis process was simplified, and there was a reduction in the amount of 2,3-epoxypropyl trimethyl ammonium chloride (EPTAC) used. With its excellent water solubility maintained, the relatively low degree of substitution was controlled to facilitate the cross-linking reaction. The results obtained from ¹H-NMR, FTIR spectroscopy, and XRD indicated a smooth EPTAC onto CS for the formation of N-2-HACC with 59.33% the degree of substitution (DS). According to our results, N-2-HACC could be dissolved in various organic solvents, deionized water, 1% acetic acid aqueous solution, and others at room temperature. Finally, a novel chitosan nanoparticle material was prepared using the self-assembly method with β-glycerophosphate sodium (β-GC), with excellent immune properties achieved, thus providing a new strategy for chitosan self-assembled nanoparticles. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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10 pages, 1231 KiB

Open AccessArticle

Ionic and Enzymatic Multiple-Crosslinked Nanogels for Drug Delivery

by Qian Tao, Julong Zhong, Rui Wang and Yuzhu Huang

Polymers 2021, 13(20), 3565; https://doi.org/10.3390/polym13203565 - 15 Oct 2021

Cited by 9 | Viewed by 1526

Abstract

Both ionic and enzymatic crosslink are efficient strategies for constructing network materials of high biocompatibility. Here chitosan was modified firstly and then crosslinked by these two methods for complementary advantages. The preparation methods and ionic crosslinkers can regulate the size and uniformity of [...] Read more.

Both ionic and enzymatic crosslink are efficient strategies for constructing network materials of high biocompatibility. Here chitosan was modified firstly and then crosslinked by these two methods for complementary advantages. The preparation methods and ionic crosslinkers can regulate the size and uniformity of the multiple-crosslinked nanogels. The multiple-crosslinked nanogels with the smallest size and the best uniformity was selected for the drug delivery. The drug-loading content and encapsulation efficiency were up to 35.01 and 66.82%, respectively. Their release behaviours are correlated with the pH value and the drug dosage. In general, the lower pH value and the lower drug dosage promoted the drug release. With the assistance of several kinetic models, it is found that drug diffusion plays a preponderant role in drug release, while polymer relaxation has a subtle effect. The multiple-crosslink resulting from ionic compounds and enzymes may provide a new perspective on developing novel biocompatible materials. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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18 pages, 5597 KiB

Open AccessArticle

Garcinol Encapsulated Ph-Sensitive Biodegradable Nanoparticles: A Novel Therapeutic Strategy for the Treatment of Inflammatory Bowel Disease

by Eden Mariam Jacob, Ankita Borah, Sindhu C. Pillai and D. Sakthi Kumar

Polymers 2021, 13(6), 862; https://doi.org/10.3390/polym13060862 - 11 Mar 2021

Cited by 12 | Viewed by 3715

Abstract

The emergence of pH-sensitive nanoscale particles is beneficial due to their ability to only release cargo in a colonic pH environment, which helps to directly target inflamed tissues in inflammatory bowel disease (IBD). Hence, we have designed the formulation of pH-sensitive biodegradable garcinol [...] Read more.

The emergence of pH-sensitive nanoscale particles is beneficial due to their ability to only release cargo in a colonic pH environment, which helps to directly target inflamed tissues in inflammatory bowel disease (IBD). Hence, we have designed the formulation of pH-sensitive biodegradable garcinol (GAR)-loaded poly (lactic–co–glycolic acid) (PLGA) coated with Eudragit^® S100 (ES100) (GAR-PLGA-ES100 nanoparticles (NPs)) for reducing inflammation caused by proinflammatory cytokines. The GAR-PLGA-ES100 NPs were prepared using a solvent evaporation technique and characterized for shape and surface morphology. An in vitro drug release study revealed the release of the drug specifically from NPs at the colonic pH of 7.4. The in vitro cytotoxicity of the GAR-PLGA-ES100 NPs was also evaluated and found to be highly biocompatible with CACO-2 cells. These NPs were able to reduce lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity. Inhibition of the expression of pro-inflammatory cytokine TNF-

α

, chemokine interleukin (IL)-8 and the nuclear factor kappa light chain enhancer of activated B-cells (NF-

κ

B) was observed after GAR-PLGA-ES100 NPs treatment. Therefore, our results support the idea that GAR-PLGA-ES100 NPs show substantial improvement after the release of the drug, specifically in colonic pH targeting and reduction in the activation of inflammation that leads to IBD, suggesting that GAR-PLGA-ES100 NPs are promising candidates for oral delivery to colonic inflamed tissue. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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Review

Jump to: Research

44 pages, 1632 KiB

Open AccessReview

Polymeric Nanoparticles: Exploring the Current Drug Development and Therapeutic Insight of Breast Cancer Treatment and Recommendations

by Ali Sartaj, Zufika Qamar, Farheen Fatima Qizilbash, Annu, Shadab Md, Nabil A. Alhakamy, Sanjula Baboota and Javed Ali

Polymers 2021, 13(24), 4400; https://doi.org/10.3390/polym13244400 - 15 Dec 2021

Cited by 20 | Viewed by 4051

Abstract

This manuscript aims to provide the latest update on polymeric nanoparticle drug delivery system for breast cancer treatment after 2015 and how research-oriented it is based on the available research data. Therefore, the authors have chosen breast cancer which is the most frequent [...] Read more.

This manuscript aims to provide the latest update on polymeric nanoparticle drug delivery system for breast cancer treatment after 2015 and how research-oriented it is based on the available research data. Therefore, the authors have chosen breast cancer which is the most frequent and common reason for mortality in women worldwide. The first-line treatment for breast cancer treatment is chemotherapy, apart from surgery, radiation and hormonal therapy. Chemotherapy is associated with lesser therapeutics and undesirable side effects and hence. In addition, drug resistance affects the therapeutic dose to the target site. Although various nano-based formulations have been developed for effective treatment, the polymeric nanoparticles effectively avoid the lacunae of conventional chemotherapy. There has been an effort made to understand the chemotherapy drugs and their conventional formulation-related problems for better targeting and effective drug delivery for breast cancer treatment. Thus, the polymeric nanoparticles as a strategy overcome the associated problems with resulting dose reduction, enhanced bioavailability, reduced side effects, etc. This present review has compiled the research reports published from 2015 to 2021 from different databases, such as PubMed, Google Scholar, ScienceDirect, which are related to breast cancer treatment in which the drug delivery of numerous chemotherapeutic agents alone or in combination, including phytoconstituents formulated into various polymer-based nanoparticles. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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11 pages, 1934 KiB

Open AccessReview

Serum Albumin Nanoparticles: Problems and Prospects

by Viktória Hornok

Polymers 2021, 13(21), 3759; https://doi.org/10.3390/polym13213759 - 30 Oct 2021

Cited by 40 | Viewed by 4454

Abstract

The present paper aims to summarize the results regarding serum albumin-based nanoparticles (NPs) for drug delivery purposes. In particular, it focuses on the relationship between their preparation techniques and synthesis parameters, as well as their successful clinical application. In spite of the huge [...] Read more.

The present paper aims to summarize the results regarding serum albumin-based nanoparticles (NPs) for drug delivery purposes. In particular, it focuses on the relationship between their preparation techniques and synthesis parameters, as well as their successful clinical application. In spite of the huge amount of consumed material and immaterial sources and promising possibilities, products made from different types of albumin NPs, with the exception of a few, still have not been invented. In the present paper, promising applications of serum albumin nanoparticles (SANPs) for different biomedical purposes, such as carriers, delivery systems and contrast agents, are also discussed. The most frequent utilization of the NPs for certain diseases, i.e., cancer therapy, and future prospects are also detailed in this study. Full article

(This article belongs to the Special Issue Advances in Natural or Synthetic Biomaterials for Developing Micro or Nano Drug Delivery Systems)

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