Loading of tacrolimus containing lipid based drug delivery systems into mesoporous silica for extended release

Many studies had been focused on designing tacrolimus sustained release preparations based on solid dispersion technique, but no one had tried to employ mesoporous silica as the carrier material to realize this goal. The purpose of this study was to develop a novel, simple and environmental friendly drug loading method with mesoporous silica to obtain tacrolimus sustained-release preparation. Tacrolimus was firstly dissolved in the molten mixed lipid composed of Compritol 888 ATO and Gelucire 50/13 to prepare a drug loaded lipid-based drug delivery systems(LBDDS), then the liquid LBDDS was adsorbed by mesoporous silica to transfer the liquid into solid powder, ie. the tacrolimus sustained release silica-lipid hybrid(SLH). The SLH was characterized by SEM, CLSM, XRPD and DSC, and the in vitro drug release was tested using a paddle method. SEM and CLSM observation showed that the LBDDS was efficiently distributed throughout the pores of the silica. The results of DSC and XRPD illustrated that the lipid existed inside the silica at amorphous state. The drug-loaded SLH showed good flowability, compressibility, compactibilty and two-phase in vitro drug release process within 24 hours, which did not change obviously even after storage at 40 °C for 10 d.The present study provided a novel and simple method to prepare tacrolimus sustained release powder, which provided a feasible solution to solidify the liquid LBDDS of not only extended drug release behavior, but also improved stability and micromeritic properties.

Cellulolytic characterization of the rumen-isolated Acinetobacter pittii ROBY and design of a potential controlled-release drug delivery system

A novel cellulolytic bacterial strain,ROBY,was isolated from a bovine rumen sample using the enrichment cul-ture method.This isolate was found to be Acinetobacter pittii,with>99%similarity according to 16S rRNA gene sequence analysis.The potential use of this strain in combination with doxorubicin(Dox)-integrated cellulose nanoparticles(Dox-CNPs)was evaluated as a proof-of-concept study for the further development of this approach as a novel controlled-release drug delivery strategy.The isolate can utilize CNPs as the sole carbon source for growth and degrade both Dox-CNPs and empty CNPs with high efficiency.Extracellular cellulases isolated from bacteria may also be used to trigger Dox release.The results also demonstrated that the release of Dox into the environment due to nanoparticle degradation in the samples incubated with Dox-CNPs significantly affected bac-terial cell viability(∼75%decrease),proving the release of Dox due to bacterial cellulase activity and suggesting the great potential of this approach for further development.

In situ sustained release hydrogel system delivering GLUT1 inhibitor and chemo-drug for cancer post-surgical treatment

Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy.In addition,application of single mode drug usually leads to unsatisfactory therapeutic out-comes.Currently,developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge.Here,we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating can-cer with minimal systemic toxicity.We demonstrated that this system can not only eliminate tumor cells in situ,but also induce abscopal effect on various tumor models.These results showed that our study provided a safe and effective strategy for clinical cancer treatment.

Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain.However,stomach irritation may occur when high doses of borneol are used.In the present work,gastrodin,the main bioactive ingredient of the traditional Chinese drug“Tianma”(Rhizoma Gastrodiae)was used as a model drug to explore reasonable application of borneol.Sustained-release solid dispersions(SRSDs)for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder.The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy,differential scanning calorimetry,and powder X-ray diffractometry.The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form.Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model.Subsequently,gastric mucosa irritation and the brain targeting of the SRSDs were evaluated.Compared with the free mixture of gastrodin and borneol,brain targeting of SRSDs was slightly weaker(brain targeting index:1.83 vs.2.09),but stomach irritation obviously reduced.Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.

Fighting type 2 diabetes: Formulation strategies for peptide-based therapeutics

Diabetes mellitus is a major health problem with increasing prevalence at a global level.The discovery of insulin in the early 1900 s represented a major breakthrough in diabetes management,with further milestones being subsequently achieved with the identification of glucagon-like peptide-1(GLP-1)and the introduction of GLP-1 receptor agonists(GLP-1 RAs)in clinical practice.Moreover,the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption.However,current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation.In this review,we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration.

Advances in Study on Three-dimensional Printing in Pharmaceutics

Three dimensional printing（3DP） is a solid freeform fabrication technology which employs powder processing and a liquid binder material in the construction of parts in a layer-wise manner. 3DP can accommodate much geometric outline and be made with many materials due to its unprecedented flexibility. The technology can control over the material composition, microstructure and surface texture so it attracts great attentions in the pharmaceutics field. 3DP can offer many novel strategies and approaches for the research and is widely focused in the field of the controlled-release drug delivery systems. Through consulting a large number of documents the current development and the technical characteristics of 3DP in pharmaceutics field are discussed and reviewed. It is expected that 3DP technique may play a tremendous role in pharmaceutics field in the future.Three dimensional printing （3DP） is a solid freeform fabrication technology which employs powder processing and a liquid binder material in the construction of parts in a layer-wise manner. 3DP can accommodate much geometric outline and be made with many materials due to its unprecedented flexibility. The technology can control over the material composition, microstructure and surface texture so it attracts great attentions in the pharmaceutics field. 3DP can offer many novel strategies and approaches for the research and is widely focused in the field of the controlled-release drug delivery systems. Through consulting a large number of documents the current development and the technical characteristics of 3DP in pharmaceutics field are discussed and reviewed. It is expected that 3DP technique may play a tremendous role in pharmaceutics field in the future.