Cell penetrating peptides as an innovative approach for drug delivery; then, present and the future

Santosh Bashyal,노규빈,금태광,최영욱,이상길 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.3

With the rapid development of biotechnology, various macromolecules as therapeutic agents have made drug delivery an important field of research. However, these are being commercialized as injection form. Due to low patient compliance, various non-invasive routes emerge as a promising strategy. Cell penetrating peptides (CPPs) have shown to assist in efficient and non-toxic manner. They provide ample evidence to deliver of many cargoes ranging from small molecules to proteins and even nanocarriers for various applications. This review briefly discusses about introduction of CPPs, history, cellular uptake mechanisms and various possible alternative routes for CPP-conjugated drug delivery system. It also aims to give a perspective on present status of CPP-mediated research, clinical development, possible obstacles as well as future opportunities. Thus, development of novel CPPs that are safe, tissue-specific and highly efficient will be exemplified and become ideal vehicles for therapeutic delivery in near future.

Facilitated permeation of insulin across TR146 cells by cholic acid derivatives-modified elastic bilosomes

Bashyal, Santosh,Seo, Jo-Eun,Keum, Taekwang,Noh, Gyubin,Choi, Young Wook,Lee, Sangkil Dove Medical Press 2018 International journal of nanomedicine Vol.13 No.-

<P><B>Background</B></P><P>Buccal delivery of insulin is still a challenging issue for the researchers due to the presence of permeability barrier (buccal mucosa) in the buccal cavity. The main objective of this study was to investigate the safety, effectiveness, and potential of various liposomes containing different bile salts to improve the permeation of insulin across in vitro TR146 buccal cell layers.</P><P><B>Methods</B></P><P>Elastic bilosomes containing soy lecithin and bile salt edge activators (sodium cholate [SC], sodium taurocholate [STC], sodium glycocholate [SGC], sodium deoxyglycocholate [SDGC], or sodium deoxytaurocholate [SDTC]) were fabricated by thin-film hydration method. The prepared liposomes were characterized, and in vitro permeation studies were performed. The fluorescein isothiocyanate-insulin-loaded elastic bilosomes were used to evaluate the quantitative and qualitative cellular uptake studies.</P><P><B>Results</B></P><P>The prepared elastic bilosomes had a particle size and an entrapment efficiency of ~140–150 nm and 66%–78%, respectively. SDGC-lipo (SDGC-incorporated liposome) was observed to be the most superior with an enhancement ratio (ER) of 5.24 (<I>P</I><0.001). The SC-incorporated liposome (SC-lipo) and SDTC-incorporated liposome (SDTC-lipo) also led to a significant enhancement with ERs of 3.20 and 3.10 (<I>P</I><0.05), respectively, compared with insulin solution. These results were further supported by quantitative and qualitative cellular uptake studies performed employing fluorescence-activated cell sorting analysis and confocal microscopy, respectively. The relative median fluorescence intensity values of elastic bilosomes were counted in the order of SDGC-lipo > SC-lipo > SDTC-lipo > SGC-incorporated liposome > STC-incorporated liposome, and similarity in the permeability profile of the employed elastic bilosomes was noted.</P><P><B>Conclusion</B></P><P>This study presents the employment of various derivatives of cholic acid-loaded elastic bilosomes as a promising strategy to enhance the permeation of insulin through buccal route.</P>

Delivery of biopharmaceuticals using combination of liposome and iontophoresis: a review

Santosh Bashyal,이상길 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.7

Non-invasive route for the delivery of biopharmaceuticals is one of the interesting areas in drug delivery systems. Since stratum corneum is regarded as an effective physical barrier to permeation of high molecular weight biopharmaceuticals, several methods have been studied for overcoming this problem and enhancing their permeation. The one technique for better transdermal delivery is to use drug carriers such as microemulsions, nanoemulsions, solid lipid nanoparticles and liposomes. These carriers can facilitate the permeation of drugs by modifying physicochemical characteristics of entrapped ingredient. Liposomes are used as potential drug carriers to enhance the percutaneous absorption of various biopharmaceuticals. Iontophoresis is another enhancing method to increase the biomembrane permeability of ionic or charged compounds using electric potential. The new strategies combining liposomes and iontophoresis technique are increasing rapidly in the field of drug delivery and possess additional benefits. It is possible to deliver neutral drugs by entrapping them in charged vehicle and their flux can be enhanced by iontophoresis. Thus, combination of liposome and iontophoresis can be effective means for transdermal permeation of biopharmaceuticals in a non-invasive and sustainable fashion.

Preparation and the skin permeation characteristics of rhEGF (recombinant human epidermal growth factor) loaded nano-liposome

전상옥,( Santosh Bashyal ),서조은,오동호,이상길 한국공업화학회 2015 한국공업화학회 연구논문 초록집 Vol.2015 No.1

Recombinant human epidermal growth factor (rhEGF) was encapsulated into nano-liposomes (NLs) system for topical delivery. The rhEGF-loaded NLs were prepared using a high pressure homogenization method. Morphology and overall particle distribution of NLs were investigated using transmission electron microscopy (TEM) and high resolution microscope (CytoVivaTM). Particle size, zeta (z) potential and encapsulation efficiency were measured and the percutaneous delivery of NLs was evaluated using Franz diffusion cells and immunofluorescence confocal laser scanning microscopy (CLSM). The mean particle size, z potential and encapsulation efficiency of the NLs were 155.57±2.59 nm, -57.92±4.35 mV and 9.00±0.39%, respectively. TEM and microscopic analysis showed spherical, very even-sized vesicles approximately 150 nm. The skin permeation and localization of rhEGF were enhanced by NLs. CLSM image analysis provided that the NLs enhanced the permeation and localization of rhEGF in rat skin by facilitating entry through pores of skin.

Recent progress in hydrophobic ion-pairing and lipid-based drug delivery systems for enhanced oral delivery of biopharmaceuticals

노규빈,금태광,Bashyal Santosh,Seo Jo-Eun,Shrawani Lamichhane,Kim Jeong Hwan,이상길 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.1

Background The biopharmaceuticals market has grown rapidly in recent years owing to the low toxicity and high therapeutic efficacy of peptide and protein drugs. However, due to their low stability, biopharmaceuticals have to be administrated via invasive routes, and there is an unmet need for alternative routes. The most familiar and preferred alternative route of administration is the oral route; however, peptide and protein drugs are readily affected by the harsh gastrointestinal environment, resulting in low oral bioavailability. Lipid-based drug delivery systems (LDDSs) for oral administration protect the incorporated drugs and enhance their absorption in the GI tract. However, only lipophilic substances can be stably incorporated in LDDSs, and hydrophilic peptides and proteins require lipidation via, e.g., hydrophobic ion pairing (HIP). Area covered This review discusses the issues that hamper the oral administration of peptides and proteins and introduces HIP and LDDSs as strategies to overcome these. The principle of HIP complexation, the parameters to be considered for complexation, and the various counterions used are described. As for LDDSs, the advantages of self-emulsifying drug delivery systems (SEDDSs), which are suitable for oral peptide and protein delivery, and in vivo study results are described. Expert opinion HIP complexes are prepared based on an understanding of the characteristics of drugs and counterions. HIP complexes of peptides and proteins in the oil phase of SEDDSs are protected from the GI environment and therefore, improved absorption is expected. Although their fundamental mechanisms remain unclear and require further study, HIPincorporated SEDDSs provide a potential strategy for oral peptide and protein delivery.

Enhanced topical delivery of fish scale collagen employing negatively surface-modified nanoliposome

서조은,김민주,전상옥,오동호,윤규형,최영욱,Santosh Bashyal,이상길 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.3

In this study, we investigated the effect of fish scale collage (FSC) on type I procollagen expression in cultured human dermal fibroblasts using real-time polymerase chain reaction and ELISA, under normal and UV exposure condition. Also, FSC encapsulated negatively surface modified nanoliposome ( NLsurf mod) was fabricated, and the physicochemical characteristics of the liposomes and skin permeation properties were evaluated. FSC increased type I procollagen mRNA and protein expression in human dermal fibroblasts. The mean particle size, zeta potential value and encapsulation efficiency of the NLsurf mod were about 175 nm, −44 mV and 11%, respectively. The skin localization effect was enhanced by NLsurf mod. Conclusively, FSC is able to elevate the type I procollagen expression in human dermal fibroblasts and FSC-loaded NLsurf mod would be a good candidate for the topical delivery of FSC.

Vaccine adjuvants: smart components to boost the immune system

Rakesh Bastola,Gyubin Noh,금태광,Santosh Bashyal,서조은,최재웅,오연수,조영식,이상길 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.11

Vaccination is an effective approach to preventthe consequences of infectious diseases. Vaccinesstrengthen immunity and make individuals resistant toinfections with pathogens. Although conventional vaccinesare highly immunogenic, they are associated with somesafety issues. Subunit vaccines are safe, but they requireadjuvants to stimulate the immune system because of theirweaker immunogenicity. Adjuvants are entities incorporatedinto vaccines to increase the immunogenic responsesof antigens. They play a crucial role in increasing thepotency and efficacy of vaccines. Different adjuvants havedifferent modes of action; therefore, a better understandingof their immunology could provide guidance for thedevelopment of novel adjuvants. Numerous studies havebeen conducted using different types of adjuvants tocharacterize their potency and safety; however, in practice,only few are used in human or animal vaccines. Thisreview aims to introduce the different modes of action ofadjuvants and give insight into the types of adjuvants thatpossess the greatest potential for adjuvanticity.

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

Shrawani Lamichhane,Jo-Eun Seo,Taekwang Keum,Gyubin Noh,Santosh Bashyal,Seong-Wan Cho,Eun-Hee Lee,Sangkil Lee 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.1

Improving the aqueous solubility of poorlysoluble compounds have been a major issue in the pharmaceuticalindustry. In the present study, binary amorphoussolid dispersions (SDs) of Coenzyme Q10 (CoQ 10 ), a biopharmaceuticsclassifi cation system (BCS) II compound andSoluplus ® were prepared to enhance the solubility and pharmacokineticproperties compared to crystalline CoQ 10 . SDswere prepared with diff erent ratios of CoQ 10 and Soluplus ®(1:3, 1:5, and 1:7) using spray drying technology, and thephysicochemical properties of the SDs were evaluated. X-raypowder diff raction, diff erential scanning calorimetry, andscanning electron microscopy suggested the conversion ofthe crystalline form of CoQ 10 to a binary amorphous systemin the SDs. Fourier transform infrared spectroscopy revealedno potential interactions between CoQ 10 and Soluplus ® . The solubility of the optimal SD formulation (SD 1:7)was approximately 9000-fold higher than that of crystallineCoQ 10, and the increment was Soluplus ® concentrationdependent. As a result, optimized SD 1:7 also showed significantly enhanced dissolution rate where maximum drugrelease was observed within 30 min in two diff erent dissolutionmedia. Moreover, in contrast to crystalline CoQ 10, CoQ 10 SDs showed improved pharmacokinetic parameters. Thus, the SD 1:7 formulation is expected to improve biopharmaceuticalproperties and therapeutic effi cacy of CoQ 10 .