Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization

2016 ◽  
Vol 31 (6) ◽  
pp. 923-932 ◽  
Author(s):  
Xiaoyan Wang ◽  
Yu Zhang ◽  
Wei Xue ◽  
Hong Wang ◽  
Xiaozhong Qiu ◽  
...  

In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50–200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50–200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50–200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 50
Author(s):  
Sennan Xu ◽  
Lingjie Ke ◽  
Sichen Zhao ◽  
Zhiguo Li ◽  
Yang Xiao ◽  
...  

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.


Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2920
Author(s):  
Ameeduzzafar Zafar ◽  
Syed Sarim Imam ◽  
Nabil K. Alruwaili ◽  
Omar Awad Alsaidan ◽  
Mohammed H. Elkomy ◽  
...  

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.


Vaccine ◽  
2015 ◽  
Vol 33 (42) ◽  
pp. 5623-5632 ◽  
Author(s):  
Vivek Bansal ◽  
Manoj Kumar ◽  
Arun Bhardwaj ◽  
H.G. Brahmne ◽  
Harpal Singh

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2674
Author(s):  
Giulia Morello ◽  
Alessandro Polini ◽  
Francesca Scalera ◽  
Riccardo Rizzo ◽  
Giuseppe Gigli ◽  
...  

In recent years, growing attention has been directed to the development of 3D in vitro tissue models for the study of the physiopathological mechanisms behind organ functioning and diseases. Hydrogels, acting as 3D supporting architectures, allow cells to organize spatially more closely to what they physiologically experience in vivo. In this scenario, natural polymer hybrid hydrogels display marked biocompatibility and versatility, representing valid biomaterials for 3D in vitro studies. Here, thermosensitive injectable hydrogels constituted by chitosan and pectin were designed. We exploited the feature of chitosan to thermally undergo sol–gel transition upon the addition of salts, forming a compound that incorporates pectin into a semi-interpenetrating polymer network (semi-IPN). Three salt solutions were tested, namely, beta-glycerophosphate (βGP), phosphate buffer (PB) and sodium hydrogen carbonate (SHC). The hydrogel formulations (i) were injectable at room temperature, (ii) gelled at 37 °C and (iii) presented a physiological pH, suitable for cell encapsulation. Hydrogels were stable in culture conditions, were able to retain a high water amount and displayed an open and highly interconnected porosity and suitable mechanical properties, with Young’s modulus values in the range of soft biological tissues. The developed chitosan/pectin system can be successfully used as a 3D in vitro platform for studying tissue physiopathology.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renato Meneghetti Peres ◽  
Jéssica Maiara Leme Sousa ◽  
Mariana Oliva de Oliveira ◽  
Maura Vincenza Rossi ◽  
Rene Ramos de Oliveira ◽  
...  

AbstractHerpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol–gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.


2018 ◽  
Vol 1 (3) ◽  

Prec. Nanomed. 2018 Oct;1(3):183-193. BASIC RESEARCH From the Clinical Editor: The number of women affected by cervical cancer worldwide is very significant and the disease is associated with human papilloma virus (HPV) infection. Although the use of HPV vaccines has proven to be useful in disease protection, they only work in women who have never been infected by HPV previously. Thus, the development of a therapeutic vaccine that targets HPV-infected cells is needed for women who are already infected with the virus. In this study, the authors describe the use of a self-adjuvating polymer-based delivery system for the development of a therapeutic vaccine. Therefore, while efforts are progressing, vaccine candidates are still required against late stage cervical cancer via improving the vaccine delivery system. Authors demonstrate that the combination of polymer-based and liposome delivery systems may be effective without the use of additional adjuvant and with just a single dose immunization. This finding has potential importance for other cancer vaccines as well. Prec. Nanomed. 2018 Oct;1(3):173-182 POTENTIAL CLINICAL SIGNIFICANCE From the Clinical Editor: The treatment of triple-negative breast cancer is often difficult due to frequent resistance to doxorubicin. Using different nano-formulations based on sol-gel technology to encapsulate doxorubicin, the authors here showed enhanced dose-response metrics and tumor cell kill of these cancer cells due to an increased drug accumulation in the local tumor environment. This platform shows early promise in terms of eventual clinical translatability. Prec. Nanomed. 2018 Oct;1(3):194-207. BASIC RESEARCH From the Clinical Editor: Surgical resection remains the main treatment modality for pancreatic cancer. Thus, the ability to delineate the tumor accurately during operation is important to ensure all tumor cells are resected. Here, the authors describe the development of a multimodal imaging probe using nanospheres to target epithelial cells of pancreatic cancer. The specificity to target only tumor cells was clearly shown in both in-vitro and in-vivo experiments. This technology may provide a new fluorescence imaging technique to help the field of surgical oncology in the future. Prec. Nanomed. 2018 Oct;1(3):208-217. BASIC RESEARCH From the Clinical Editor: Preclinical characterization of nanotechnology-based products is essential for translating innovative applications into clinics. In addition to the innate immune system complement activation plays an important role in regulating the adaptive immune response. Undesirable activation of the complement system in response to new composites may lead to hypersensitivity reactions. The authors describe the importance of mouse strain selection for in vitro complement activation analysis addressing also the existence of inter- and intraspecies variability.


RSC Advances ◽  
2017 ◽  
Vol 7 (63) ◽  
pp. 39962-39969 ◽  
Author(s):  
Yunfei Han ◽  
Qian Duan ◽  
Yanhui Li ◽  
Jian Tian

A simple and powerful vaccine delivery system was developed by electrostatic binding of chitosan-based polycation methoxy poly(ethylene glycol)–chitosan–poly(l-lysine) (mPEG–CS–PLL) with ovalbumin (OVA) and cytosine–phosphate–guanine (CpG).


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