Effect of cargo properties on in situ forming implant behavior determined by noninvasive ultrasound imaging

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.

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Enhanced drug loading of in situ forming gels for oral mucositis pain control

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120225 ◽

2021 ◽

Vol 595 ◽

pp. 120225

Author(s):

Tingting Li ◽

Rajesh V. Lalla ◽

Diane J. Burgess

Keyword(s):

Oral Mucositis ◽

Pain Control ◽

Drug Loading ◽

In Situ Forming

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Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Copolymers for the Formulation of In Situ Forming Depot Long-Acting Injectables

Pharmaceutics ◽

10.3390/pharmaceutics13050605 ◽

2021 ◽

Vol 13 (5) ◽

pp. 605

Author(s):

Marie-Emérentienne Cagnon ◽

Silvio Curia ◽

Juliette Serindoux ◽

Jean-Manuel Cros ◽

Feifei Ng ◽

...

Keyword(s):

Ethylene Glycol ◽

Surface Erosion ◽

Sustained Delivery ◽

Trimethylene Carbonate ◽

Poly Ethylene Glycol ◽

In Situ Forming ◽

Poly Ethylene ◽

Long Acting

This article describes the utilization of (methoxy)poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) ((m)PEG–PTMC) diblock and triblock copolymers for the formulation of in situ forming depot long-acting injectables by solvent exchange. The results shown in this manuscript demonstrate that it is possible to achieve long-term drug deliveries from suspension formulations prepared with these copolymers, with release durations up to several months in vitro. The utilization of copolymers with different PEG and PTMC molecular weights affords to modulate the release profile and duration. A pharmacokinetic study in rats with meloxicam confirmed the feasibility of achieving at least 28 days of sustained delivery by using this technology while showing good local tolerability in the subcutaneous environment. The characterization of the depots at the end of the in vivo study suggests that the rapid phase exchange upon administration and the surface erosion of the resulting depots are driving the delivery kinetics from suspension formulations. Due to the widely accepted utilization of meloxicam as an analgesic drug for animal care, the results shown in this article are of special interest for the development of veterinary products aiming at a very long-term sustained delivery of this therapeutic molecule.

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Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute

Regenerative Biomaterials ◽

10.1093/rb/rbaa036 ◽

2020 ◽

Author(s):

Isabel Pereira ◽

José Eduardo Pereira ◽

Luís Maltez ◽

Alexandra Rodrigues ◽

Catarina Rodrigues ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Substitute ◽

Bone Substitutes ◽

Multipotent Mesenchymal Stromal Cells ◽

Micro Computed Tomography ◽

Synthetic Bone Substitute ◽

In Situ Forming ◽

Bioactive Agents ◽

In Situ Forming Hydrogels

Abstract The development of injectable bone substitutes (IBS) have obtained great importance in the bone regeneration field, as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies. In this scenario, the association of injectable hydrogels and bone graft granules is emerging as a well-established trend. Particularly, in situ forming hydrogels have arisen as a new IBS generation. An in situ forming and injectable dextrin-based hydrogel (HG) was developed, aiming to act as a carrier of granular bone substitutes and bioactive agents. In this work, the HG was associated to a granular bone substitute (Bonelike®) and implanted in goat critical-sized calvarial defects (14 mm) for 3, 6 and 12 weeks. The results showed that HG improved the handling properties of the Bonelike® granules and did not affect its osteoconductive features, neither impairing the bone regeneration process. Human multipotent mesenchymal stromal cells from the umbilical cord, extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS. These bioactive agents did not enhance the new bone formation significantly under the conditions tested, according to micro-computed tomography and histological analysis.

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