Injectable in-situ Forming Depot Of Doxycycline Hyclate/α-Cyclodextrin Complex using PLGA for Periodontitis Treatment: Preparation, Charac-terization, and In-Vitro Evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Elham Khodaverdi ◽  
Farhad Eisvand ◽  
Mohammad Sina Nezami ◽  
Seyedeh Nesa Rezaeian Shiadeh ◽  
Hossein Kamali ◽  
...  
Keyword(s):  
Complex Form ◽  
Docking Studies ◽  
Morphological Properties ◽  
Burst Release ◽  
Cyclodextrin Complex ◽  
Doxycycline Hyclate ◽  
Scanning Calorimetry ◽  
In Situ Forming

Background:: Doxycycline (DOX) is used in treating a bacterial infection, especially for periodontitis treatment. Objective: To reduce irritation of DOX for subgingival administration and increase the chemical stability and against enzy-matic, the complex of α-cyclodextrin with DOX was prepared and loaded into injectable in situ forming implant based on PLGA. Methods:: FTIR, molecular docking studies, X-ray diffraction, and differential scanning calorimetry was performed to char-acterize the DOX/α-cyclodextrin complex. Finally, the in-vitro drug release and modeling, morphological properties, and cellular cytotoxic effects were also evaluated. Results:: The stability of DOX was improved with complex than pure DOX. The main advantage of the complex is the al-most complete release (96.31 ± 2.56 %) of the drug within 14 days of the implant, whereas in the formulation containing the pure DOX and the physical mixture the DOX with α-cyclodextrin release is reached to 70.18 ± 3.61 % and 77.03 ± 3.56 %, respectively. This trend is due to elevate of DOX stability in the DOX/ α-cyclodextrin complex form within PLGA implant that confirmed by the results of stability. Conclusion:: Our results were indicative that the formulation containing DOX/α-cyclodextrin complex was biocompatible and sustained-release with minimum initial burst release.

Long-lasting in situ forming Implant loaded with Bupivacaine: Investigation on the Polymeric and Non-polymeric Carrier and Solvent Effect

2021 ◽  
Vol 18 ◽  
Author(s):  
Saeed Bazraee ◽  
Hamid Mobedi ◽  
Arezuo Mashak ◽  
Ahmad Jamshidi
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Fickian Diffusion ◽  
Morphological Properties ◽  
Burst Release ◽  
Solvent Concentration ◽  
Drug Release Profile ◽  
In Situ Forming

Introduction: Typically, in situ forming implants utilize Poly (lactide-co-glycolide) (PLGA) as a carrier and N-methyl-2-pyrrolidone (NMP) as a solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations. Objective: The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia. Methods: We used Sucrose acetate isobutyrate (SAIB), PLGA 50:50, and a mixture of them as carriers to compare the release behavior. Besides, the effect of PLGA molecular weight (RG 502H, RG 503H, and RG 504H), solvent type, and solvent concentration on the drug release profile was evaluated. The formulations were characterized by investigating their in-vitro drug release, rheological properties, solubility, and DSC, in addition to their morphological properties. Furthermore, the Korsmeyer-Peppas and Weibull models were applied to the experimental data. The results revealed that a mixture of SAIB and PLGA compared to using them solely can extend the Bupivacaine HCl release from 3 days to two weeks. Results: The DSC results demonstrated the compatibility of the mixture by showing a single Tg. The formulation with NMP had a higher burst release and final release in comparison with other solvents by 30% and 96%, respectively. Increasing the solvent concentration from 12% to 32% raised the drug release significantly, which confirmed the larger porosity in the morphology results. From the Korsmeyer-Peppas model, the mechanism of drug release is predicted to be non-Fickian diffusion.

Antibacterial Agent-Incorporated Cholesterol Phase Inversion-Based In Situ Forming Matrix for Crevicular Pocket Delivery

2020 ◽  
Vol 859 ◽  
pp. 107-112
Author(s):  
Orn Setthajindalert ◽  
Khine Sabel Aung ◽  
Juree Charoenteeraboon ◽  
Arissarakorn Sirinamaratana ◽  
Thawatchai Phaechamud
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Antibacterial Agent ◽  
Phase Inversion ◽  
Gingival Crevicular Fluid ◽  
Diffusion Method ◽  
Burst Release ◽  
Doxycycline Hyclate

Phase inversion in situ forming matrix is one of the promising drug delivery systems for periodontitis treatment owing to the prospective high antimicrobial agent level in the gingival crevicular fluid. Typically, this drug delivery system is a fluid polymeric solution that could change simultaneously to matrix-like after injection into aqueous physiological environment. The main propose of the current study was to achieve successful development of antibacterial agent-incorporated cholesterol phase inversion in situ forming matrix for crevicular pocket delivery. In this study, cholesterol was used as a fat matrix former, while N-methyl pyrrolidone (NMP) was used as the solvent and menthol was used as co-solvent. The 10%w/w metronidazole or doxycycline hyclate was employed as the active compounds. The developed formula were evaluated for viscosity and rheological behavior, antimicrobial activity using cup agar diffusion method and in vitro drug release using dialysis tube method. The consistency index from rheological test of doxycycline hyclate and metronidazole-loaded in situ forming matrices was not significantly different (p<0.05). Interestingly, the viscosity of all formula was quite low; thus, this characteristic provoked an ease of injection. They inhibited against Porphyromonasgingivalis efficiently more than cholesterol in situ forming matrix base (p<0.05). Drug release from systems loaded with doxycycline hyclate and metronidazole were rapid and nearly not different. Owing to the apparent efficiently inhibition against Porphyromonasgingivalis the in situ forming matrix loading doxycline hyclate was selected for further development to minimize the burst release and to prolong the drug release.

An in-situ forming implant formulation of naltrexone with minimum initial burst release using mixture of PLGA copolymers and ethyl heptanoate as an additive: In-vitro, ex-vivo, and in-vivo release evaluation

2018 ◽  
Vol 47 ◽  
pp. 95-105 ◽  
Author(s):  
Hossein Kamali ◽  
Elham Khodaverdi ◽  
Farzin Hadizadeh ◽  
Rezvan Yazdian-Robati ◽  
Ali Haghbin ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Burst Release ◽  
Initial Burst ◽  
Initial Burst Release ◽  
In Situ Forming ◽  
In Vivo Release

In Vitro and In Vivo Drug Release from a Novel In Situ Forming Drug Delivery System

2007 ◽  
Vol 25 (6) ◽  
pp. 1347-1354 ◽  
Author(s):  
Heiko Kranz ◽  
Erol Yilmaz ◽  
Gayle A. Brazeau ◽  
Roland Bodmeier
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
In Situ Forming

In-vitro, ex-vivo, and in-vivo release evaluation of in situ forming buprenorphine implants using mixture of PLGA copolymers and additives

2018 ◽  
Vol 68 (16) ◽  
pp. 965-977 ◽  
Author(s):  
Hossein Kamali ◽  
Elham Khodaverdi ◽  
Farzin Hadizadeh ◽  
Seyed Ahmad Mohajeri ◽  
Younes Kamali ◽  
...  
Keyword(s):  
Ex Vivo ◽  
In Situ Forming ◽  
In Vivo Release

scholarly journals In Vitro Biocompatibility and Osteoblast Differentiation of an Injectable Chitosan/Nano-Hydroxyapatite/Collagen Scaffold

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Chen ◽  
Zhi Huang ◽  
Xiaoming Li ◽  
Songjian Li ◽  
Zhilai Zhou ◽  
...  
Keyword(s):  
Collagen Scaffold ◽  
Reaction Cell ◽  
In Vitro Biocompatibility ◽  
In Situ Forming ◽  
Osteogenic Markers ◽  
Polymerase Chain ◽  
Cell Expression

The purpose of this study was to evaluate the in vitro cell biocompatibility of an in situ forming composite consisting of chitosan (CS), nano-hydroxyapatite and collagen (nHAC), which has a complex hierarchical structure similar to natural bone. MC3T3-E1 mouse calvarial preosteoblasts were cultured on the surface of the injectable CS/nHAC and CS scaffold. The proliferations of seeded MC3T3-E1 were investigated for 10 days. Cytotoxicity, cell proliferation, and cell expression of osteogenic markers such as alkaline phosphatase (ALP), type 1 collagen (COL-1), RUNX-2, and osteocalcin (OCN) were examined by biochemical assay and reverse transcription polymerase chain reaction. Cell viability and total cellularity (measured by dsDNA) were similar between the two scaffold groups. However, ALP, COL-1, OCN, and RUNX-2 production were significantly greater when osteoblasts were cultured on CS/nHAC scaffolds. The increase in osteogenic markers production on CS/nHAC scaffolds indicated that these scaffolds were superior to chitosan-only scaffolds in facilitating osteoblast mineralization. These results demonstrate the potential of the CS/nHAC scaffolds to be used in bone tissue engineering.

scholarly journals Preparation of a Sustained Release Drug Delivery System for Dexamethasone by a Thermosensitive, In Situ Forming Hydrogel for Use in Differentiation of Dental Pulp

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Elham Khodaverdi ◽  
Fatemeh Kheirandish ◽  
Farnaz Sadat Mirzazadeh Tekie ◽  
Bibi Zahra Khashyarmanesh ◽  
Farzin Hadizadeh ◽  
...  
Keyword(s):  
Phase Transition ◽  
Transition Temperature ◽  
Phase Transition Temperature ◽  
Delivery System ◽  
In Vitro Release ◽  
In Situ Forming ◽  
Release Study ◽  
Vitro Release

In situ forming delivery systems composed of block copolymers are attracting substantial attention due to their ease of use, biocompatibility, and biodegradability. In this study, the thermoresponsive triblock copolymer PLGA-PEG-PLGA was studied as a dexamethasone delivery system. Dexamethasone, a synthetic glucocorticoid, is used clinically to improve inflammation, pain, and the hyperemesis of chemotherapy, and it is applied experimentally as a differentiation factor in tissue engineering. PLGA-PEG-PLGA was synthesised under microwave irradiation for 5 min. The obtained copolymer was characterised to determine its structure and phase transition temperature. An in vitro release study was conducted for various copolymer structures and drug concentrations. The yield of the reaction and HNMR analysis confirmed the appropriateness of the microwave-assisted method for PLGA-PEG-PLGA synthesis. Phase transition temperature was affected by the drug molecule as well as by the copolymer concentration and structure. An in vitro release study demonstrated that release occurs mainly by diffusion and does not depend on the copolymer structure or dexamethasone concentration.

Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration

Planta Medica ◽  
2019 ◽  
Vol 85 (16) ◽  
pp. 1233-1241
Author(s):  
Michael Kirchinger ◽  
Lara Bieler ◽  
Julia Tevini ◽  
Michael Vogl ◽  
Elisabeth Haschke-Becher ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmaceutical Research ◽  
Water Soluble ◽  
Complexing Agents ◽  
Cyclodextrin Complex ◽  
Scanning Calorimetry ◽  
In Vivo Experiments ◽  
Strong Candidate

AbstractThe chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-β-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-β-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-β-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-β-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.

Sucrose Acetate Isobutyrate as an In situ Forming Implant for Sustained Release of Local Anesthetics

2019 ◽  
Vol 16 (4) ◽  
pp. 331-340
Author(s):  
Hanmei Li ◽  
Yuling Xu ◽  
Yuna Tong ◽  
Yin Dan ◽  
Tingting Zhou ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Sustained Release ◽  
Local Anesthetics ◽  
Subcutaneous Injection ◽  
In Vitro Release ◽  
Pharmacokinetic Analysis ◽  
Burst Release

Objective: In this study, an injectable Sucrose Acetate Isobutyrate (SAIB) drug delivery system (SADS) was designed and fabricated for the sustained release of Ropivacaine (RP) to prolong the duration of local anesthesia. Methods: By mixing SAIB, RP, and N-methyl-2-pyrrolidone, the SADS was prepared in a sol state with low viscosity before injection. After subcutaneous injection, the pre-gel solution underwent gelation in situ to form a drug-released depot. Result: The in vitro release profiles and in vivo pharmacokinetic analysis indicated that RP-SADS had suitable controlled release properties. Particularly, the RP-SADS significantly reduced the initial burst release after subcutaneous injection in rats. Conclusion: In a pharmacodynamic analysis of rats, the duration of nerve blockade was prolonged by over 3-fold for the RP-SADS formulation compared to RP solution. Additionally, RP-SADS showed good biocompatibility in vitro and in vivo. Thus, the SADS-based depot technology is a safe drug delivery strategy for the sustained release of local anesthetics with long-term analgesia effects.

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