Effect of Polymer Permeability and Solvent Removal Rate on In Situ Forming Implants: Drug Burst Release and Microstructure

Zhang, Xiaowei; Yang, Liqun; Zhang, Chong; Liu, Danhua; Meng, Siwei; Zhang, Wei; Meng, Shengnan

doi:10.3390/pharmaceutics11100520

Cited by 31 publications

(20 citation statements)

References 44 publications

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“…In order to clinically translate, the limit of DMSO and pharmacokinetic of VCM depending on an application site should be considered. DMSO has been utilized as a medium of many dosage forms including in situ forming implants [ 11 , 91 ], in situ forming microparticle [ 92 ], and intra-arthricular injection [ 93 ]. 50% w/w DMSO (RIMSO-50 ® ) is approved by US FDA for treatment of human interstitial/chronic cystitis as well as various topical dosage form containing DMSO for flap ischemia (60% DMSO), herpes zoster (5% idoxuridine in DMSO), and injection site extravasation (99% DMSO) treatment [ 94 ].…”

Section: Resultsmentioning

confidence: 99%

Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery

et al. 2020

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In recent years, the world has faced the issue of antibiotic resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in various treatments and control of infections. Biocompatible materials with saturated fatty acids of different chain lengths (C8–C18) were studied as matrix formers of localized injectable vancomycin HCl (VCM)-loaded antisolvent-induced in situ forming matrices. The series of fatty acid-based in situ forming matrices showed a low viscosity (5.47–13.97 cPs) and pH value in the range of 5.16–6.78, with high injectability through a 27-G needle (1.55–3.12 N). The preparations exhibited low tolerance to high concentrations of KH2PO4 solution (1.88–5.42% v/v) and depicted an electrical potential change during phase transformation. Their phase transition and matrix formation at the microscopic and macroscopic levels depended on the chain length of fatty acids and solvent characteristics. The VCM release pattern depended on the nucleation/crystallization and solvent exchange behaviors of the delivery system. The 35% w/v of C12–C16 fatty acid-based in situ forming matrix prolonged the VCM release over seven days in which C12, C14, C16 –based formulation reached 56, 84, and 85% cumulative drug release at 7th day. The release data fitted well with Higuchi’s model. The developed formulations presented efficient antimicrobial activities against standard S. aureus, MRSA, Escherichia coli, and Candida albicans. Hence, VCM-loaded antisolvent-induced fatty acid-based in situ forming matrix is a potential local delivery system for the treatment of local Gram-positive infection sites, such as joints, eyes, dermis of surgery sites, etc., in the future.

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Section: Resultsmentioning

confidence: 99%

Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery

et al. 2020

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“…Biodegradable polymer membranes studied in the current work are suitable for producing stent coatings and implants with a prolonged and controlled release of medications into surrounding tissues. Many attempts have been made in the recent two decades to immobilize various substances in membranes [31][32][33], but there are still no examples of the controlled release of substances heavier than 10 kDa from the membrane [34]. In the present study, a controlled release of 46 kDa substance was achieved.…”

Section: Discussionmentioning

confidence: 71%

Polylactide-Based Stent Coatings: Biodegradable Polymeric Coatings Capable of Maintaining Sustained Release of the Thrombolytic Enzyme Prourokinase

et al. 2019

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The novelty of the study is the development, creation, and investigation of biodegradable polymeric membranes based on polylactide, that are capable of directed release of large molecular weight biomolecules, particularly, prourokinase protein (MW = 46 kDa). Prourokinase is a medication with significant thrombolytic activity. The created membranes possess the required mechanical properties (relative extension value from 2% to 10%, tensile strength from 40 to 85 MPa). The membranes are biodegradable, but in the absence of living cells in a water solution they decompose by less than 10% in half a year. The created membranes are capable of controlled prourokinase release into intercellular space, and the total enzymatic activity of prourokinase does not decrease by more than 12%. The daily release of prourokinase from one square centimeter of the membrane ranges from 1 to 40 μg per day depending on the technique of membrane preparation. The membranes have no acute toxic effect on cells accreting these surfaces de novo. The number of viable cells is at least 96%−97% of the overall cell count. The mitotic index of the cells growing on the surface of the polymeric films comprised around 1.5%. Histological examination did not reveal any disorders in tissues of the animals after the implantation of polymer membranes based on polylactide, both alone and as components of stent cover. Implantation of stents covered with prourokinase-containing polymers led to the formation of a mature connective tissue capsule that is thicker than in the case of uncovered stents. Thus, various polylactide-based biodegradable polymeric membranes possessing the required mechanical properties and capable of prolonged and directed release of prourokinase macromolecules are developed and investigated in the study.

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“…В качестве примера можно привести измерение предела прочности на разрыв и процента относительного удлинения [17], оценку пористости образца и шероховатости его поверх ности, проведение механического теста на сжатие [19]. Необходимость данных исследований обусловлена тем, что проникающие криопротекторы потенциально способны влиять на материал скаффолда, так как многие из них (ДМСО, формамид, этиленгликоль) являются полярными органическими растворителями и могут при определенных условиях стимулировать деградацию полимера или вызывать изменения морфологии поверхности [32,33].…”

Section: оценка эффективности криоконсервации тикunclassified

Cryopreservation of tissue-engineered constructs in regenerative medicine

Arutyunyan¹,

Dubovaya²

2021

Clin. Exp. Morphology

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The transplantation of artificial tissues and organs is gradually becoming a part of our reality. At the same time, researchers are facing a problem common to all transplantologists, i.e. the need for a long-term storage of a biomedical product (transplant) without losing its properties. The possibility to cryopreserve cells adhered to various scaffolds' surface was first presented about 20 years ago. However, the data on the technology as a whole remains unsystematized and controversial. This review aimed to analyze the literature on tissue-engineered constructs (TEC) cryopreservation of different scientific groups to create a unified approach in assessing the technique's efficacy necessary for further regenerative medicine development. The comparison of studies on TEC cryopreservation conducted by various research groups is hampered not only by the lack of standardized protocols but also by different approaches to assessing the result. As experimental data were accumulated, the cryopreservation efficacy was reassessed from meeting the basic requirements for the structure preservation (thawed TEC retains its integrity, cells are partially alive and attached to the matrix) to focusing on the final result (thawed TEC retains its functional properties and is ready to be transplanted). Many of the currently used in vitro research methods presented in the review allow one to look for new ways of increasing the TEC cryopreservation efficacy; however, in our opinion, the next step on the way to introducing the technology into clinical practice should be research on experimental animals. Keywords: tissue engineered construction, cryopreservation, efficacy estimation

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Effect of Polymer Permeability and Solvent Removal Rate on In Situ Forming Implants: Drug Burst Release and Microstructure

Cited by 31 publications

References 44 publications

Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery

Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery

Polylactide-Based Stent Coatings: Biodegradable Polymeric Coatings Capable of Maintaining Sustained Release of the Thrombolytic Enzyme Prourokinase

Cryopreservation of tissue-engineered constructs in regenerative medicine

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