Acetate Isobutyrate Research Articles

Carbohydrate based biomarkers enable hybrid near infrared fluorescence and 64Cu based radio-guidance for improved surgical precision.

Increasing numbers of lung tumors are identified at early disease stages by diagnostic imaging in screening programs, but difficulties in locating these during surgical intervention has prevented an improved treatment outcome. Surgical biomarkers that are visible on diagnostic images, and that provide the surgeon with real-time image guidance during the intervention are thus highly warranted to bridge diagnostic precision into enhanced therapeutic outcome. In this paper, a liquid soft tissue marker for near infrared fluorescence and radio-guidance is presented. The biocompatible marker is based on the carbohydrate ester, sucrose acetate isobutyrate, ethanol, and a multifunctional naphthalocyanine dye, which enable near infrared fluorescence image-guided resection at short, medium and long tissue depths. Naphthalocyanine dyes have high quantum yields and may further act as chelators of radionuclides. Upon injection of the liquid marker, a gel-like depot is formed in situ at the site of injection, wherein the fluorescent dye and radionuclide is retained. The radiolabeled markers were optimized for minimal fluorescence quenching and high retention of the positron emission tomography radionuclide 64Cu. The performance of the radiolabeled marker was tested in vivo in mice, where it displayed high photostability over a period of 4 weeks, and high retention of 64Cu for 48 hours. The retention and biodistribution of 64Cu was quantified via PET/CT, and the fluorescence emission by an in vivo imaging system. The presented data demonstrate proof-of-concept for naphthalocyanine markers as multimodal imaging agents that can bridge the precision of diagnostic imaging into surgical interventions.

Fabrication of biocompatible porous SAIB/silk fibroin scaffolds using ionic liquids

This work brings new perspectives for the use of Sucrose Acetate Isobutyrate (SAIB) for tissue engineering scaffolding products. Porous SAIB/Silk fibroin (SF) scaffolds with tunable properties were synthesized using ionic liquids.

Sucrose acetate isobutyrate based nanovesicles: A promising platform for drug delivery and bioavailability enhancement

Sucrose acetate isobutyrate based nanovesicles (SBN) were designed to enhance the Ticagrelor poor bioavailability (36%). SBN were formulated with different ratios of sucrose acetate isobutyrate and Poloxamer 407 and tested for particle size, polydispersity index, zeta potential and entrapment efficiency. The desirable formula composed of 5.52:1 surfactant: drug ratio and 0.1:1 sucrose acetate isobutyrate: Poloxamer 407 ratio with 0.77 desirability value as determined by the Design-Expert® software. Then, the optimized formula was lyophilized and compressed into tablets to maintain its physical stability and facilitate the oral administration. The lyophilized formula and the compressed nanostructed tablets were tested for the in vitro drug release versus the pure drug powder and the marketed product (Brilique®), where a significant enhancement in the drug dissolution rate and extent was observed, either in the sink or non-sink conditions. Based on the pharmacokinetic study conducted on rabbits, the nanostructured tablets showed a significant increase in the drug absorption extent expressed by an area under the plasma concentration-time curve of 4163.52 ng h/mL where the latter for the marketed product was only 2824.16 ng h/mL. In conclusion, the prepared nanostructed tablets achieved 150% relative bioavailability assuring the enhancement of TR solubility and absorption after being loaded into the optimized SBN formula.

Development of Abuse-Deterrent Formulations Using Sucrose Acetate Isobutyrate.

The objective of the present investigation was to understand the effect of sucrose acetate isobutyrate (SAIB) on abuse-deterrent properties (ADPs) of abuse-deterrent formulations (ADFs) based on Polyox™. SAIB would enhance ADPs of Polyox™-based formulations due to its glassy liquid and hydrophobic properties. Formulations were prepared by granulation followed by compression and heat curing at 90°C. The formulations were evaluated for surface morphology, hardness, manipulation in coffee grinder, particle size distribution, drug (pseudoephedrine hydrochloride) extraction in water, alcohol, 0.1N HCl, 0.1N NaOH at room temperature and elevated temperature using microwave and oven, syringeability and injectability, and dissolution. The heat curing of formulations significantly increased the hardness (> 490N). Addition of SAIB imparted elasticity to formulations and decreased brittleness as indicated by lower values of work done and gradient compared to control formulations. After grinding, about 7.7-25.6% of the powder remained on the sieve (1mm pore opening), D90 was 53.1-136.7μm more, and Q (fraction < 500μm) was 17.8-40.7% less in SAIB-based formulations compared to control formulations. Drug extraction between control and test intact formulations was similar. However, drug extraction was 23.9-42.5% (water), 20.6-26.1% (0.1N HCl), and 37.4-50.6% (0.1N NaOH) less in SAIB-based powder cured and uncured formulations compared to control formulations. Dissolution varied from 65.6 ± 4.2 to 97.6 ± 4.0% in 9h from the formulations. In conclusion, addition of SAIB to Polyox™-based ADFs has synergistic effect on ADPs. This would further decrease potential of drug abuse/misuse by various routes.

Ionic Liquid-Mediated Processing of SAIB-Chitin Scaffolds

This study proposes a green and innovative ionic liquid (IL) methodology for processing sucrose acetate isobutyrate (SAIB) porous structures for tissue engineering. The solubilization of SAIB in an...

Effect of microsphere size on the drug release and experimental characterization of an electrospun naringin‐loaded microsphere/sucrose acetate isobutyrate (SAIB) depot

The aims of this study were to prepare different sizes of electrospun naringin‐loaded microspheres (Ng‐ms) and investigate the effects of the particle size of these microspheres on drug release from naringin‐loaded microsphere/sucrose acetate isobutyrate (Ng‐m‐SAIB) hybrid depots to develop an improved drug delivery system for tissue engineering. Different sizes of microspheres were produced using electrospray methods by controlling electrospinning parameters. The Ng‐m‐SAIB depots were prepared by dispersing Ng‐ms in SAIB depots. The morphology and size distributions of the electrospun Ng‐ms were characterized by polarizing microscopy and scanning electron microscopy (SEM). To better understand the release behavior of Ng‐m‐SAIB, the porosity of SAIB depots was measured. Consequently, both small (2.51 ± 0.191 μm) and large (5.03 ± 0.172 μm) microspheres exhibited smooth surfaces and good monodispersity. The initial and long‐term drug release rates of the large microspheres were lower than those of small microspheres. On the first day after 2.5‐μm and 5‐μm Ng‐m‐SAIB depots were produced, the burst release reduced dramatically from 68.79% to 3.30% and from 63.20% to 0.00%, respectively. After 92 days of release, the drug release rate of 5‐μm Ng‐m‐SAIB was still lower than that of 2.5‐μm Ng‐m‐SAIB, with values of 58.54% and 63.93%, respectively. These results demonstrate that drug release from Ng‐m‐SAIB depots can be tailored solely by varying the size of the microspheres and that good drug release behavior occurred.

Influence of Additives on Thermal Properties and Morphological of Magnetorheological Elastomer

Magnetorheological elastomers (MREs) are categorized as part of the smart materials class whose rheological properties can be altered under the influence of a magnetic field. MREs are fabricated by embedding soft magnetic particles such as carbonyl iron particles (CIPs) in a rubber matrix such as silicone and natural rubber. In this project, epoxidized natural rubber (ENR-50) is used as a base material with carbonyl iron particles. Sucrose Acetate Isobutyrate (SAIB) ester is added to the formulation to improve the viscosity and enhance the MRE properties. The isotropic MRE is fabricated using two roll mill and a compression mould. Various tests comprise mechanical, morphology, thermal and magnetic tests were conducted for MRE characterization purpose. The results showed that the addition of SAIB on the MRE had reduced 53% of viscosity in the rubber matrix compared to non-ester based MRE. Dispersion of magnetic particles is improved by the addition of ester as observed through Field Emission Scanning Electron Microscope (FESEM). Additionally, the thermal stability was also improved. Tensile strength of MRE consisting SAIB ester achieved maximum strength of 12.3 MPa and an elongation of 620% compared to non-ester based MRE. Â

Development of Methamphetamine Abuse–Deterrent Formulations Using Sucrose Acetate Isobutyrate

The objective of the present research was to investigate application of sucrose acetate isobutyrate (SAIB) in the development of a meth-deterrent formulation in combination with polyethylene oxide (PolyoxTM) and hydroxypropyl methylcellulose. The formulations were prepared by granulating pseudoephedrine hydrochloride, hydroxypropyl methylcellulose, and PolyoxTM with an ethanolic solution of SAIB and compressed into tablets followed by heat curing. The tablets were characterized for surface morphology, crystallinity, drug distribution, hardness, particle size, extraction, and dissolution. Hardness increased insignificantly, surface morphology indicated cracking and crevices, and diffractograms showed an increase and a decrease in drug and PolyoxTM crystallinity, respectively, after heat curing. Pseudoephedrine hydrochloride, PolyoxTM, and SAIB distribution was uniform as indicated by near infrared image. The drug extraction varied from 69.5% to 77.8%, 90.3% to 106.5%, 51.3% to 81.2%, and 48.9% to 72.6% in water, ethanol, 0.1 N HCl, and 0.1 N NaOH, respectively. The dissolution was more than 85% in 9 h from all the formulations. Thus, the addition of SAIB to the formulation decreased the drug extraction in various solvents which has the potential to decrease abuse of pseudoephedrine formulation for methamphetamine synthesis.

Liposomal bupivacaine and novel local anesthetic formulations.

Novel preparations allowing for the extended duration of action of local anesthetics have many clinically relevant benefits. With regard to this, the development of liposomal bupivacaine has the potential to significantly impact patient care by improving perioperative pain control. The unique liposomal bilayer that encapsulates bupivacaine allows for a sustained release of local anesthetic for up to 72h after a single use and can significantly decrease postoperative opioid consumption. SABER-bupivacaine is another depot formulation that helps in sustained release of bupivacaine from an encapsulated bupivacaine in a biodegradable sucrose acetate isobutyrate biolayer. HTX-011 is an investigational extended-release local anesthetic formulation currently undergoing Phase 3 clinical trials. HTX-011 is composed of a bioerodible polymer with bupivacaine and low-dose meloxicam in which the polymer undergoes hydrolysis and allows for sustained release of bupivacaine and meloxicam for 3 days. The present investigation reviews pharmacologic considerations related to the formulation of liposomal bupivacaine, current FDA-approved indications for its use, and future extended-release local anesthetic formulations currently under investigation.

Administration of sulpiride in sucrose acetate isobutyrate (SAIB) to geldings: Duration of response and evaluation of conjugated estradiol preparations

The study aim was to investigate the usefulness of different longevity measures in Danish show jumping horses as well as potential early indicator traits for longevity in jumping. The analyses comprised jumping competition data from 9592 horses born during 1981 to 1994, 30,435 young horse records, and their pedigree. Genetic parameters and breeding values were estimated using AI-REML and mixed models including fixed effects of birth year, age at first placing, sex and number of offspring. Four longevity traits were investigated: no. years in competition from first to last entry (NYC), no. active years in competition i.e. only years with a registered start/placing (NAY), NAY plus no. foals carried to term by mares (NAYF), and accumulated lifetime points (LDP) combining longevity and competition success. Longevity defined as NAY was found most useful for the Danish Warmblood. The heritability of NAY was 0.11. Young horse jumping traits had moderate to high genetic correlation with longevity (rg: 0.51–0.74) and highest value as indicator trait among young horse traits (rg×rIA: 0.23–0.44). Conformation had lower informative value for longevity (highest |rg×rIA| was 0.10). Including information of young horse capacity and rideability during jumping in a multivariate analysis increased the accuracy of NAY breeding values of younger horses from 0.32 to 0.49 and increased model predictive ability compared to a univariate longevity evaluation.

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

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. 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. 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. 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.

Electrosprayed naringin-loaded microsphere/SAIB hybrid depots enhance bone formation in a mouse calvarial defect model

The burst release of active osteogenic factors, which is not beneficial to osteogenesis, is commonly encountered in bone tissue engineering. The aims of this study were to prepare naringin-loaded microsphere/sucrose acetate isobutyrate (Ng-m-SAIB) hybrid depots, reduce the burst release of naringin (Ng), and improve osteogenesis. The morphology and size distributions of electrosprayed Ng-microspheres were characterized by scanning electron microscopy (SEM). The Ng-microspheres and Ng-m-SAIB depots were characterized by Fourier transform infrared spectroscopy (FTIR) and in vitro release studies. In vitro osteoblast-microsphere interactions and in vivo osteogenesis were assessed after implantation of Ng-m-SAIB depots. The addition of sucrose acetate isobutyrate (SAIB) to monodisperse Ng-microspheres did not cause a change in the chemical structure. The performances of the microspheres in osteoblast-microsphere interactions were better when the naringin content was 4% than when it was at 2% and 6%. On the first day following the loading of Ng-microspheres (2%, 4%, and 6%) into SAIB depots, the burst release was reduced dramatically from 70.9% to 6.3%, 73.1% to 7.2%, and 73.9% to 9.9%, respectively. In addition, after 8 weeks, the new bone formation rate in the calvarial defects of SD rats receiving Ng-m-SAIB was 53.1% compared to 21.2% for the control group and 16.1% for the microsphere-SAIB group. These results demonstrated that Ng-m-SAIB hybrid depots may have promise in bone regeneration applications.

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

Oral drug delivery is an attractive noninvasive alternative to injectables. However, oral delivery of biopharmaceuticals is highly challenging due to low stability during transit in the gastrointestinal tract (GIT), resulting in low systemic bioavailability. Thus, novel formulation strategies are essential to overcome this challenge. An interesting approach is increasing retention in the GIT by utilizing mucoadhesive biomaterials as excipients. Here, we explored the potential of the GRAS excipient sucrose acetate isobutyrate (SAIB) to obtain mucoadhesion in vivo. Mucoadhesive properties of a 90% SAIB/10% EtOH (w/w) drug delivery system (DDS) were assessed using a biosimilar mucus model and evaluation of rheological behavior after immersion in biosimilar intestinal fluid. To ease readability of this manuscript, we will refer to this as SAIB DDS. The effect of SAIB DDS on cell viability and epithelial membrane integrity was tested in vitro prior to in vivo studies that were conducted using SPECT/CT imaging in rats. When combining SAIB DDS with biosimilar mucus, increased viscosity was observed due to secondary interactions between biosimilar mucus and sucrose ester predicting considerable mucoadhesion. Mucoadhesion was confirmed in vivo, as radiolabeled insulin entrapped in SAIB DDS, remained in the small intestine for up to 22 h after administration. Moreover, the integrity of the system was investigated using the dynamic gastric model under conditions simulating the chemical composition of stomach fluid and physical shear stress in the antrum under fasted conditions. In conclusion, SAIB is an interesting and safe biomaterial to promote high mucoadhesion in the GIT after oral administration.

Visualization of the tumor cavity after lumpectomy of breast cancer for postoperative radiotherapy

To visualize the tumor cavity after lumpectomy, the tumor cavity was coated with the liquid tissue marker sucrose acetate isobutyrate (SAIB) with its radiopaque electron dense SAIB analogue (x-SAIB) and assessed for radiotherapy planning. SAIB/x-SAIB enhanced the confidence for target structure definition. Tissue displacement after oncoplasty may be revealed by SAIB/x-SAIB.

Polymeric and Non Polymeric Injectable In-situ Forming Implant Systems for Sustained Delivery of Lornoxicam: In vitro and In vivo Evaluation.

Formulation of injectable In situ forming implant (ISI) systems of lornoxicam for dental and postoperative pain management to decrease dosing frequency and increase patient compliance. Polymeric in situ implant solutions were prepared using different concentrations and inherent viscosities of Poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG) using 22X4 factorial experimental design. Nonpolymeric systems were prepared using different concentrations of lipids like cetyl alcohol and stearyl alcohol and also sucrose acetate isobutyrate (SAIB) using 32 factorial experimental design. In vitro release study, rheological measurement, syringeability assessment and effect of γ-sterilization were used for evaluation of the prepared formulae. In vivo pharmacokinetic study of lornoxicam from the most optimum formula was conducted in a rabbit model using HPLC analysis of blood samples. Polymeric systems showed high burst release followed by very slow release rate over 72 hours. Formula I 24 (containing SAIB 80% (w/w)) showed relatively low burst release followed by diffusion controlled release pattern, low viscosity, Newtonian flow behavior and good syringeability. γ- sterilization had no significant effect on the in vitro release and the physical nature of the most optimum formula. In vivo study concluded that intramuscularly injected In situ implant formula I 24 showed prolonged release pattern compared to the marketed product which was indicated by the increased Tmax and the extended mean residence time. Lornoxicam ISI systems could be promising as convenient injectable sustained release delivery systems for dental and postoperative pain management.

Performance of Magnetorheological Elastomer Based Silicone/SAIB

This study introduces a sucrose acetate isobutyrate (SAIB) as an additive of magnetorheological elastomers (MREs) to be added in silicone rubber matrix and carbonyl iron particles (CIPs) as their filler. The CIPs were fixed at 60 wt% and two types of MREs sample were fabricated which are isotropic and anisotropic. Rheological properties related to shear storage modulus were measured using a rheometer (MCR 302, Anton Paar). The experimental results demonstrated that the magnetorheological (MR) effect of anisotropic MREs-based Silicone/SAIB was 126 % as compared to isotropic MREs-based Silicone/SAIB, 64%. The fabricated MREs samples were frequency and strain dependent. The relative MR effect for both samples showed decreasing trend with the increment of strain amplitude and excitation frequency.

Effects of Various Methods of Sulpiride Administration on Prolactin Release in Horses

Four experiments assessed factors affecting prolactin responses to sulpiride administration in horses. Experiment 1 compared the efficacy of the (−) enantiomer of sulpiride to that of the commonly used (+/−) racemic mixture. Mares were used in an 8 × 8 Latin square to compare the prolactin responses to four doses of levosulpiride to four corresponding doses of the racemic mixture at twice the dose. Responses at each dose indicated equal and similar (P > .1) responses. Experiment 2 compared the efficacy of 1 gram of orally administered racemic sulpiride to 100 mg of intramuscularly injected sulpiride in oil in mares primed with 50 mg of estradiol cypionate (ECP). Prolactin responses in groups receiving sulpiride were robust but similar in magnitude with minor differences in timing. In experiment 3, ECP-primed geldings received subcutaneous injections of 1.8 grams racemic sulpiride in vegetable shortening in one of three sites: the neck, the back below the withers, or the lower girth region; control geldings received no sulpiride. Prolactin responses to sulpiride lasted a minimum of 96 hours. In experiment 4, prolactin responses to 3 g of racemic sulpiride in vegetable shortening were compared to similar injections (3 g) in 5 mL of sucrose acetate isobutyrate (SAIB; SucroMate) or just SAIB (control) in ECP-primed geldings. Controls had no prolactin response to SucroMate, whereas both treatment groups had extended prolactin responses lasting at least 10 days. It is concluded that prolactin responses to sulpiride in horses can be greatly extended by using hydrophobic vehicles like vegetable shortening or SAIB.

Performance of magnetorheological elastomer based green epoxidized natural rubber/sucrose acetate isobutyrate hybrid matrix

This study introduces a sucrose acetate isobutyrate (SAIB) as a novel additive of magnetorheological elastomers (MREs). The MREs utilized an epoxidized natural rubber (ENR) as the matrix and carbonyl iron particles (CIPs) as their filler. The CIPs were fixed at 60 wt%. The viscosity of the compound was observed using a viscometer. Meanwhile, the microstructures were observed by using field emission scanning electron microscope (FESEM). Rheological properties regarding shear storage modulus were measured by using a rheometer (MCR 302, Anton Paar). The experimental results demonstrated that the MREs-based ENR/SAIB had a decrement in their viscosity by 40% reduction. Moreover, the magnetorheological (MR) effect increased by 23% as the increment of magnetic fields. The morphological photograph showed that the CIPs embedded well within the matrix. The fabricated MREs samples were strain dependent, where all MREs samples exhibit the deteriorating trend when increasing the strain amplitude.

Delivery of radix ophiopogonis polysaccharide via sucrose acetate isobutyrate-based in situ forming systems alone or combined with its mono-PEGylation

This work aimed to achieve long-lasting delivery of radix ophiopogonis polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the ‘90%SAIB/10% solvent’ system was used, the mean residence time (MRT) of ROP was prolonged by 4.3 5 ∼ 7.00 times and the initial release rate was reduced significantly. However, this system was only suitable for days-long sustained release of ROP in short-term therapy. As to the ‘SAIB/additives/solvent’ system containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide-co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to months-long (16–60 d) smooth release of ROP could be achieved by varying the concentration (10–30%) and molecular weight (MW) of PLGA (10–50 kDa) or by employing a moderate MW of PEGylated ROP (∼20 or ∼30 kDa). With further increasing the conjugate MW to ∼40 kDa, the contribution of drug elimination to its plasma retention seemed to surpass that of the SAIB-based system, resulting in that the system no longer had an obvious influence on the in vivo behavior of the conjugate. Besides, the results of host response confirmed that with less solvent being used, the SAIB-based systems showed a higher biocompatibility than the PLGA-based systems, suggesting that they could be freely chosen in the prevention and/or cure of chronic diseases.

Development of Long Acting Depot Injection of Iloperidone by SABER Technology

The present investigations report the application of SABER® technology in the development of a one-month depot injection of iloperidone. SABER® is a new in situ gel formulation technology for sustained release drug delivery, which precludes the use of large amounts of toxic organic solvents in the formulation. Traditionally in the in situ gel forming technology-based depot injections, expensive polymers such as polylactic acid and poly(lactic-co-glycolic acid), and a class 2 solvent like N-methyl-2-pyrrolidone have been used to control the rate of drug release and dissolve the drug and polymer, respectively. In the present investigations, however, no such release retarding polymers were used, moreover, the formulation was developed using a limited amount of dimethylsulphoxide, a class 3 solvent. Formulation variables were optimized by D-optimal mixture design to obtain the depot formulation with a consistent drug release for one month. The composition of sucrose acetate isobutyrate, and dimethylsulphoxide were taken as input variables and cumulative drug release at various time points as response variables. The optimized formulation contained 81.718 % sucrose acetate isobutyrate and 18.282 % dimethylsulphoxide and produced a consistent drug release profile with 85.71 % cumulative drug release in 30 days without any significant burst release.