Exploring the mucoadhesive behavior of sucrose acetate isobutyrate: a novel excipient for oral delivery of biopharmaceuticals

Rønholt, Stine; Fliervoet, Lies A. L.; Fano, Mathias; Schmitt, Mechthild; Antopolski, Maxim; Urtti, Arto; Nielsen, Hanne Mørck

doi:10.1080/10717544.2019.1606866

Cited by 11 publications

(10 citation statements)

References 47 publications

(62 reference statements)

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“…Among the available sustained-release delivery systems, sucrose acetate isobutyrate (SAIB) is one of the most prospective systems with biodegradability and injectability, and it is usually considered safe by the U.S. Food and Drug Administration (FDA) (Wang et al., 2018 ; Harloff-Helleberg et al., 2019 ). Furthermore, the viscosity of the SAIB can be dramatically reduced when mixing with a little amount of solvent, for example, ethanol, allowing the SAIB to be easily inject using small needles.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the viscosity of the SAIB can be dramatically reduced when mixing with a little amount of solvent, for example, ethanol, allowing the SAIB to be easily inject using small needles. Upon injection, the solvent diffuses from the depot into body fluid, resulting in a highly viscous SAIB depot from where the drug can be released in a sustained manner (Wang et al., 2018 ; Harloff-Helleberg et al., 2019 ; Yang et al., 2019 ). However, burst release still existed in the application of SAIB (Park & Lee, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment

et al. 2021

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Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects; however, high levels of MINO administered during the treatment halt the formation of new bone. Therefore, the purpose of the present study was to prepare a MINO-microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis. Uniform microspheres, approximately 5 µm size, with a slightly rough surface and different MINO loading (10, 12, and 14%) were prepared, and the microspheres were added into SAIB, after which the burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively, and the release from all the MINO-microspheres/SAIB hybrid depots lasted for 77 days. In addition, cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most and was subsequently used in vivo experiments. Moreover, in the model of ligatured-induced periodontitis in SD rats, the MINO-microsphere/SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue. Additionally, it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) and promoted the expression of osteoprotegerin (OPG).. These results indicated that the MINO-microsphere/SAIB hybrid depot might be promising in the treatment of periodontitis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment

et al. 2021

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“…PLGA, an FDA-approved copolymer, is widely used in drug delivery and is known by its good biocompatibility and biodegradability. On the other hand, SAIB is used as a food additive and has been approved by US FDA at a daily intake of up to 20 mg/kg of body weight [ 49 ]. However, the use of SAIB in a drug delivery system, such as the one developed in this work, would require its biocompatibility and low toxicity with the surrounding tissues at the local injection site.…”

Section: Resultsmentioning

confidence: 99%

In Situ-Forming Microparticles for Controlled Release of Rivastigmine: In Vitro Optimization and In Vivo Evaluation

et al. 2021

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In this work, sucrose acetate isobutyrate (SAIB) and polylactic co-glycolic acid (PLGA) were used alone or in combination as a matrix-former (MF) to prepare long-acting injectable rivastigmine (RV) in situ-forming microparticles (ISM). RV-ISM were prepared by the emulsification of an internal phase, containing the drug and the matrix former(s), into an external oily phase containing a stabilizer. The statistical design, Central Composite Design (CCD), was adopted as a quality by design (QbD) approach to optimize the formulation of RV-ISM systems. The fabricated RV-ISM systems was designed to minimize the initial burst drug release and maximize the sustainment of RV release from the ISM and ease of injection. The influence of critical formulation variables such as the matrix-former to drug (MF/D) ratio and SAIB to PLGA (S/P) ratio in the internal phase with respect to critical quality attributes (CQAs), such as the percentage drug release within the first day (Q1), the time required for 50% drug release (T50%) and the rate of injection, were studied using the CCD. The optimal RV-ISM system with the highest desirability value (0.74) was predicted to have an MF/D ratio of 11.7:1 (w/w) and an S/P ratio of 1.64:1 (w/w). The optimal RV-ISM system was assessed for its release profile, injectability, rheological properties, morphology, effect on cell viability, tolerance to γ-sterilization and in vivo performance in male albino rabbits. In vitro release studies revealed that the optimal RV-ISM system released 100% of its drug content throughout a release period of 30 days with only 15.5% drug release within the first day (Q1) and T50% of 13.09 days. Moreover, the optimal system showed a high injection rate of 1.012 mL/min, pseudoplastic flow, uniform spherical globules with homogenous particle size, minimal cytotoxicity and high tolerability to γ-sterilization. In vivo pharmacokinetic (PK) studies revealed that the rate of absorption of RV from the optimal RV-ISM system was controlled compared to a drug solution following either intramuscular (IM) or subcutaneous (SC) injection. Furthermore, the optimal RV-ISM was found to follow flip-flop PK with poor correlation between in vitro release and in vivo findings. These findings suggest that the optimal RV-ISM is a promising tool to achieve a sustained release therapy for RV; however, further investigation is still required to optimize the in vivo performance of RV-ISM.

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“…Consequently, if using these methods, more animals are used to assess the in vivo faith of a DDS 386 over time. Alternative methods such as single photon emission computed tomography/computerized 387 tomography (SPECT/CT) can be considered, and here the labeled DDS is administered via the chosen route 388 of administration, and the in vivo faith of the administered sample is followed over time [209]. A significant 389 drawback of this approach is, however, that it requires very expensive equipment and radiolabeling of the 390 test compounds immediately prior to administration.…”

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confidence: 99%

“…[209]. Fluorescence detection in animals is also possible, but can be difficult and also demands labeling of…”

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confidence: 99%

Animal models for evaluation of oral delivery of biopharmaceuticals

Rønholt

Nielsen

2017

Journal of Controlled Release

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Biopharmaceuticals are increasingly important for patients and the pharmaceutical industry due to their ability to treat and, in some cases, even cure chronic and potentially life-threatening diseases. Most biopharmaceuticals are administered by injection, but intensive focus on development of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals primarily with examples on insulin.

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Exploring the mucoadhesive behavior of sucrose acetate isobutyrate: a novel excipient for oral delivery of biopharmaceuticals

Cited by 11 publications

References 47 publications

Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment

Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment

In Situ-Forming Microparticles for Controlled Release of Rivastigmine: In Vitro Optimization and In Vivo Evaluation

Animal models for evaluation of oral delivery of biopharmaceuticals

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