EGF, a veteran of wound healing: highlights on its mode of action, clinical applications with focus on wound treatment, and recent drug delivery strategies.

Epidermal growth factor (EGF) has been used in wound management and regenerative medicine since the late 1980s. It has been widely utilized for a long time and still is because of its excellent tolerability and efficacy. EGF has many applications in tissue engineering, cancer therapy, lung diseases, gastric ulcers, and wound healing. Nevertheless, its in vivo and during storage stability is a primary concern. This review focuses on the topical use of EGF, especially in chronic wound healing, the emerging use of biomaterials to deliver it, and future research possibilities. To successfully deliver EGF to wounds, a delivery system that is proteolytically resistant and stable over the long term is required. Biomaterials are an area of interest for the development of such systems. These systems may be used in non-healing wounds such as diabetic foot ulcers, pressure ulcers, and burns. In these pathologies, EGF can reduce the risk of amputation of the lower extremities, as it accelerates the wound healing process. Furthermore, appropriate delivery system would also stabilize and control the EGF release profile in a wound. Several in vitro and in vivo studies have already proven the efficacy of such systems in the above-mentioned types of wounds. Moreover, several formulations such as ointments and intralesional injections are already available on the market. However, these products are still problematic in terms of inadequate diffusion of EGF, low bioavailability storage conditions, and shelf-life. This review discusses the nano formulations comprising biomaterials infused with EGF which could be a promising delivery system for chronic wound healing in the future.

Optimized self-microemulsifying drug delivery system improves the oral bioavailability and brain delivery of coenzyme Q10.

Our study aimed to develop a self-microemulsifying drug delivery system for the poorly aqueous-soluble drug Coenzyme Q10, to improve the dissolution and the oral bioavailability. Excipients were selected based on their Coenzyme Q10 solubility, and their concentrations were set for the optimization of the microemulsion by using a D-optimal mixture design to achieve a minimum droplet size and a maximum solubility of Coenzyme Q10 within 15 min. The optimized formulation was composed of an oil (omega-3; 38.55%), a co-surfactant (Lauroglycol® 90; 31.42%), and a surfactant (Gelucire® 44/14; 30%) and exhibited a mean droplet size of 237.6 ± 5.8 nm and a drug solubilization (at 15 min) of 16 ± 2.48%. The drug dissolution of the optimized formulation conducted over 8 h in phosphate buffer medium (pH 6.8) was significantly higher when compared to that of the Coenzyme Q10 suspension. A pharmacokinetic study in rats revealed a 4.5-fold and a 4.1-fold increase in the area under curve and the peak plasma concentration values generated by the optimized formulation respectively, as compared to the Coenzyme Q10 suspension. A Coenzyme Q10 brain distribution study revealed a higher Coenzyme Q10 distribution in the brains of rats treated with the optimized formulation than the Coenzyme Q10 suspension. Coenzyme Q10-loaded self microemulsifying drug delivery system was successfully formulated and optimized by a response surface methodology based on a D-optimal mixture design and could be used as a delivery vehicle for the enhancement of the oral bioavailability and brain distribution of poorly soluble drugs such as Coenzyme Q10.

Enhancing solubility and bioavailability of coenzyme Q10: formulation of solid dispersions using Soluplus® as a carrier.

Improving the aqueous solubility of poorly soluble compounds have been a major issue in the pharmaceutical industry. In the present study, binary amorphous solid dispersions (SDs) of Coenzyme Q10 (CoQ10), a biopharmaceutics classification system (BCS) II compound and Soluplus® were prepared to enhance the solubility and pharmacokinetic properties compared to crystalline CoQ10. SDs were prepared with different ratios of CoQ10 and Soluplus® (1:3, 1:5, and 1:7) using spray drying technology, and the physicochemical properties of the SDs were evaluated. X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy suggested the conversion of the crystalline form of CoQ10 to a binary amorphous system in the SDs. Fourier transform infrared spectroscopy revealed no potential interactions between CoQ10 and Soluplus®. The solubility of the optimal SD formulation (SD 1:7) was approximately 9000-fold higher than that of crystalline CoQ10, and the increment was Soluplus® concentration dependent. As a result, optimized SD 1:7 also showed significantly enhanced dissolution rate where maximum drug release was observed within 30 min in two different dissolution media. Moreover, in contrast to crystalline CoQ10, CoQ10 SDs showed improved pharmacokinetic parameters. Thus, the SD 1:7 formulation is expected to improve biopharmaceutical properties and therapeutic efficacy of CoQ10.

Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation.

BACKGROUND: The clinical use of therapeutic peptides has been limited because of their inefficient delivery approaches and, therefore, inadequate delivery to target sites. Buccal administration of therapeutic peptides offers patients a potential alternative to the current invasive routes of administration. PURPOSE: The aim of the study was to fabricate hydrophobic ion-pairing (HIP)-nanocomplexes (C1 and C2) utilizing anionic bile salts and cationic peptides, and to assess their permeability across TR146 buccal cell layers and porcine buccal tissue. METHODS: C1 and C2-nanocomplexes were fabricated using the HIP approach. In addition, their physiochemical and morphological attributes, in vitro and ex vivo permeability properties, and qualitative and quantitative cellular uptake were evaluated and compared. The localization of C1 and C2-nanocomplexes in porcine buccal tissue was determined using confocal laser scanning microscopy. RESULTS: The C1-nanocomplex was the superior nanocarrier and significantly enhanced the transport of insulin across TR146 cell layers and porcine buccal tissue, exhibiting a 3.00- and 51.76-fold increase in permeability coefficient, respectively, when compared with insulin solution (p < 0.01). C1-nanocomplex was more efficient than C2-nanocomplex at facilitating insulin permeability, with a 2.18- and 27.64-fold increase across TR146 cell layers and porcine buccal tissue, respectively. The C1-nanocomplex demonstrated immense uptake and localization of insulin in TR146 cells and porcine buccal tissue, as evidenced by a highly intense fluorescence in TR146 cells, and a great shift of fluorescence intensity towards the inner region of buccal tissue over time. The increase in fluorescence intensity was observed in the order of C1 > C2 > insulin solution. CONCLUSION: In this study, we highlighted the efficacy of potential nanocarriers in addressing the daunting issues associated with the invasive administration of insulin and indicated a promising strategy for the buccal administration and delivery of this life-saving peptide hormone.

Development, Characterization, and Ex Vivo Assessment of Elastic Liposomes for Enhancing the Buccal Delivery of Insulin.

Buccal drug delivery is a suitable alternative to invasive routes of drug administration. The buccal administration of insulin for the management of diabetes has received substantial attention worldwide. The main aim of this study was to develop and characterize elastic liposomes and assess their permeability across porcine buccal tissues. Sodium-cholate-incorporated elastic liposomes (SC-EL) and sodium-glycodeoxycholate-incorporated elastic liposomes (SGDC-EL) were prepared using the thin-film hydration method. The prepared liposomes were characterized and their ex vivo permeability attributes were investigated. The distribution of the SC-EL and SGDC-EL across porcine buccal tissues was evaluated using confocal laser scanning microscopy (CLSM). The SGDC-EL were the most superior nanocarriers since they significantly enhanced the permeation of insulin across porcine buccal tissues, displaying a 4.33-fold increase in the permeability coefficient compared with the insulin solution. Compared with the SC-EL, the SGDC-EL were better at facilitating insulin permeability, with a 3.70-fold increase in the permeability coefficient across porcine buccal tissue. These findings were further corroborated based on bioimaging analysis using CLSM. SGDC-ELs showed the greatest fluorescence intensity in buccal tissues, as evidenced by the greater shift of fluorescence intensity toward the inner buccal tissue over time. The fluorescence intensity ranked as follows: SGDC-EL > SC-EL > FITC-insulin solution. Conclusively, this study highlighted the potential nanocarriers for enhancing the buccal permeability of insulin.

Albumin nanoscience: homing nanotechnology enabling targeted drug delivery and therapy.

Albumin is a biocompatible, non-immunogenic and versatile drug carrier system. It has been widely used to extend the half-life, enhance stability, provide protection from degradation and allow specific targeting of therapeutic agents to various disease states. Understanding the role of albumin as a drug delivery and distribution system has increased remarkably in the recent years from the development of albumin-binding prodrugs to albumin as a drug carrier system. The extraordinary surface property of albumin makes it possible to bind various endogenous and exogenous molecules. This review succinctly deals with several albumin-drug conjugates and nanoparticles along with their preparation techniques and focuses on surface-modified albumin and targeting of albumin formulation to specific organs and tissues. It also summarizes research efforts on albumin nanoparticles used for delivering drugs to tumor cells and describes their role in permeation through tumor vasculature and in receptor mediated endocytosis, which is also described in this review. The versatility of albumin and ease of preparation makes it a suitable drug carrier system, swhich is the major objective of this review.

Customized Novel Design of 3D Printed Pregabalin Tablets for Intra-Gastric Floating and Controlled Release Using Fused Deposition Modeling.

Three-dimensional (3D) printing has been recently employed in the design and formulation of various dosage forms with the aim of on-demand manufacturing and personalized medicine. In this study, we formulated a floating sustained release system using fused deposition modeling (FDM). Filaments were prepared using hypromellose acetate succinate (HPMCAS), polyethylene glycol (PEG 400) and pregabalin as the active ingredient. Cylindrical tablets with infill percentages of 25%, 50% and 75% were designed and printed with the FDM printer. An optimized formulation (F6) was designed with a closed bottom layer and a partially opened top layer. Filaments and tablets were characterized by means of fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and thermogravimetric analysis (TGA). The results show that the processing condition did not have a significant effect on the stability of the drug and the crystallinity of the drug remained even after printing. A dissolution study revealed that drug release is faster in an open system with low infill percentage compared to closed systems and open systems with a high infill ratio. The optimized formulation (F6) with partially opened top layer showed zero-order drug release. The results show that FDM printing is suitable for the formulation of floating dosage form with the desired drug release profile.

Complex formulations, simple techniques: Can 3D printing technology be the Midas touch in pharmaceutical industry?

3D printing is a method of rapid prototyping and manufacturing in which materials are deposited onto one another in layers to produce a three-dimensional object. Although 3D printing was developed in the 1980s and the technology has found widespread industrial applications for production from automotive parts to machine tools, its application in pharmaceutical area is still limited. However, the potential of 3D printing in the pharmaceutical industry is now being recognized. The ability of 3D printing to produce medications to exact specifications tailored to the needs of individual patients has indicated the possibility of developing personalized medicines. The technology allows dosage forms to be precisely printed in various shapes, sizes and textures that are difficult to produce using traditional techniques. However, there are various challenges associated with the proper application of 3D printing in the pharmaceutical sector which should be overcome to exploit the scope of this technology. In this review, an overview is provided on the various 3D printing technologies used in fabrication of complex dosage forms along with their feasibility and limitations.