Design of cationic microspheres based on aminated gelatin for controlled release of peptide and protein drugs.
ABSTRACT Two different types of cationized microspheres based on a native cationic gelatin (NGMS) and aminated gelatin with ethylendiamine (CGMS) were investigated for the controlled release of three model acidic peptide/protein drugs with different molecular weights (MWs) and isoelectric points (IEPs). Recombinant human (rh)-insulin (MW: 5.8 kDa, IEP: 5.3), bovine milk lactoalbumin, BMLA (MW: 14 kDa, IEP: 4.3), and bovine serum albumin (BSA MW: 67 kDa, IEP: 4.9) were used as model acidic peptide/protein drugs. The in vitro release profiles of these acidic peptide/protein drugs from NGMS and CGMS were compared and different periods of cross-linking were obtained. The slower release of these acidic peptide/protein drugs from CGMS compared with those from NGMS with cross-linking for 48 hr. was caused by the suppression of burst release during the initial phase. The degree of suppression of burst release of the three peptide/protein drugs during the initial phase by CGMS was in the following order: (rh)-insulin > BMLA > BSA. The release of insulin with a lower molecular weight from CGMS was particularly suppressed compared with the other two drugs with higher molecular weights in the initial phase. The control of the release rate of acidic peptide/protein drugs from gelatin microsphere can be achieved by amination of gelatin. Therefore, CGMS is useful for the controlled release of acidic peptide/ protein drugs.
SourceAvailable from: Katharigatta Narayanaswamy Venugopala[Show abstract] [Hide abstract]
ABSTRACT: Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer–Peppas kinetic model with an R2 of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).Drug Design, Development and Therapy 01/2015; 9:273-282. DOI:10.2147/DDDT.S66654 · 3.03 Impact Factor
Article: Advanced Materials for Gene Delivery[Show abstract] [Hide abstract]
ABSTRACT: Gene therapy is a widespread and promising treatment of many diseases resulting from genetic disorders, infections and cancer. The feasibility of the gene therapy is mainly depends on the development of appropriate method and suitable vectors. For an efficient gene delivery, it is very important to use a carrier that is easy to produce, stable, non-oncogenic and non-immunogenic. Currently most of the vectors actually suffer from many problems. Therefore, the ideal gene therapy delivery system should be developed that can be easily used for highly efficient delivery and able to maintain long-term gene expression, and can be applicable to basic research as well as clinical settings. This article provides a brief over view on the concept and aim of gene delivery, the different gene delivery systems and use of different materials as a carrier in the area of gene therapy.Advanced Materials Research 07/2014; 995:29-47. DOI:10.4028/www.scientific.net/AMR.995
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ABSTRACT: One of the advances in biotechnology has been the development of the capability to produce large quantities of highly purified polypeptides and proteins. Unfortunately, the circulatory half-lives of many of these agents are short, usually of the order of minutes and the time required for a response in tissues is usually long compared to the half-life. Hence, there is always demand for polymeric systems which can deliver the proteins for prolonged period and also to protect the molecules from degradation. The present work was attempted to develop heparin-functionalized gelatin microspheres (HMS) to deliver heparin-binding growth factors particularly for wound-healing applications. The heparin conjugation was carried out using EDC/NHS coupling protocol. Heparin-binding EGF-like growth factor (HB-EGF) was loaded in HMS and its in vitro release behaviour in an environment with or without proteases was studied. The bioactivity of the HB-EGF released from the microspheres was assessed using NIH 3T3 mouse embryonic fibroblast culture. The extent of heparin modification was found to be 1.97 μmol/g of HMS and demonstrated significant protection against enzymatic degradation and sustained release of HB-EGF for more than 10 days. The bioactivity of HB-EGF released from the HMS was retained during the observed release period. The HMS was also found to be non-toxic as determined by calcein AM fluorescent staining. The overall study suggests that the HMS could be used as a growth factor’s delivery component in tissue engineering scaffolds particularly for wound-healing applications.Polymer Bulletin 03/2014; 71(4). DOI:10.1007/s00289-014-1108-3 · 1.49 Impact Factor