Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing.

CONTEXT: Growth factors act in an integrated manner to promote the wound-healing process. However, probably due to early inactivation of these molecules in the wound site, their topical administration scarcely leads to a significant improvement in chronic wound repair. OBJECTIVES: With the aim of identifying improved therapeutics, a sodium carboxymethyl chitosan-recombinant human epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed that conjugation will protect rhEGF against proteolysis and will mediate rhEGF release by α-amylase. MATERIAL AND METHODS: As hydrogels possess most of the desirable characteristics of an ideal dressing, we used our previously described chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF and free rhEGF, the proliferation of fibroblasts was measured using a colorimetric assay. Additionally the stability of conjugated and free rhEGF against proteases was estimated. RESULT AND DISCUSSION: In vitro results revealed that the conjugated form exhibited more stability against proteolysis and also preserved its biological activity. Furthermore, in vivo studies were performed using an excision wound model on diabetic rats. After 15 d, the wound area in NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups and showed histological parameters equal to positive wound control group. CONCLUSION: A polymer conjugated rhEGF was developed that was more stable against proteases and reserved the biological activity of the drug. This dressing appears to be a competent candidate for chronic wound healing.

Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing.

CONTEXT: Growth factors act in an integrated manner to promote the wound-healing process. However, probably due to early inactivation of these molecules in the wound site, their topical administration scarcely leads to a significant improvement in chronic wound repair. OBJECTIVES: With the aim of identifying improved therapeutics, a sodium carboxymethyl chitosan-recombinant human epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed that conjugation will protect rhEGF against proteolysis and will mediate rhEGF release by α-amylase. MATERIAL AND METHODS: As hydrogels possess most of the desirable characteristics of an ideal dressing, we used our previously described chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF and free rhEGF, the proliferation of fibroblasts was measured using a colorimetric assay. Additionally the stability of conjugated and free rhEGF against proteases was estimated. RESULT AND DISCUSSION: In vitro results revealed that the conjugated form exhibited more stability against proteolysis and also preserved its biological activity. Furthermore, in vivo studies were performed using an excision wound model on diabetic rats. After 15 d, the wound area in NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups and showed histological parameters equal to positive wound control group. CONCLUSION: A polymer conjugated rhEGF was developed that was more stable against proteases and reserved the biological activity of the drug. This dressing appears to be a competent candidate for chronic wound healing.

Growth factor conjugation: strategies and applications.

Growth factors, first known for their essential role in the initiation of mitosis, are required for a variety of cellular processes and their localized delivery is considered as a rational approach in their therapeutic application to assure a safe and effective treatment while avoiding unwanted adverse effects. Noncovalent immobilization of growth factors as well as their covalent conjugation is amongst the most common strategies for localized delivery of growth factors. Today, immobilized and covalently conjugated growth factors are considered as a promising drug design and are widely used for protein reformulation and material design to cover the unwanted characteristics of growth factors as well as improving their functions. Selection of a suitable conjugation technique depends on the substrate chemistry and the availability of functional reactive groups in the structure of growth factor, the position of reactive groups in growth factor molecules and its relation with the receptor binding area, and the intention of creating either patterned or unpatterned conjugation. Various approaches for growth factor reformulation have been reported. This review provides an overview on chemical conjugation of growth factors and covers the relevant studies accomplished for bioconjugation of growth factors and their related application.

Fabrication and structure analysis of poly(lactide-co-glycolic acid)/silk fibroin hybrid scaffold for wound dressing applications.

Silk fibroin (SF) and poly(lactide-co-glycolic acid) (PLGA) have been proved to be invaluable polymers in the field wound healing. This study aims at optimizing the electrospinning process of those polymers to make a hybrid membrane as a chronic wounds dressing. After characterizing the scaffolds, PLGA/SF (2:1), and PLGA scaffolds were selected for further study according to their superior tensile mechanical properties. The attachment and proliferation of mouse fibroblasts (L929) on scaffolds were measured using colorimetric assay and scanning electron microscopy. Furthermore, to evaluate the wound healing effect of the scaffolds in comparison with gauze and Comfeel(®) dressings, an excision wound model was conducted on diabetic rats. On the postoperative days of 3, 6, 9, 12, and 15, residual wound area was calculated using macroscopic data. In vitro results showed that the attachment and proliferation of L929 were significantly increased on PLGA/SF (2:1) hybrid scaffold. Animal study and histopathological evaluation outcomes confirmed the in vitro results as well. On day 15, the residual wound area in PLGA/SF (2:1) hybrid membrane group was significantly smaller than PLGA and control groups. This promising scaffold has the potential to be used for the upcoming development of wound dressings with or without biological drugs.

The role of clinical pharmacy services in achieving treatment targets in Iranian haemodialysis patients.

INTRODUCTION: The number of patients suffering from chronic kidney disease (CKD) is increasing worldwide. Hyperphosphataemia and high serum calcium (Ca) and phosphorus (P) product contribute to the substantial increase in cardiovascular events in CKD patients. Although reports of CKD complications in Iranian haemodialysis (HD) patients are comparable to data from other developed countries, management of these complications has failed to meet generally accepted targets. This study evaluated the impact of clinical pharmacy services in the management of complications in HD patients. METHODS: During a six-month prospective study, clinical pharmacists conducted medical visits in the HD ward and adjusted the patients' medications according to their laboratory findings. RESULTS: Serum Ca concentration was increased in hypocalcaemia patients and decreased in hypercalcaemia patients until it reached the optimal range in both groups. A decline in serum P level was noted in hyperphosphataemia patients, although it did not reach the target range. The Ca × P product decreased in patients with Ca × P > 55 mg2/dL2. Although it did not reach the goal, there was an increase and decrease in serum intact parathyroid hormone (iPTH) concentration in suboptimal and supraoptimal range patients, respectively. Serum Ca, P and iPTH levels did not change in patients with optimal values at the initiation of the study. Haemoglobin concentration increased in anaemic patients and serum ferritin reached target values in all patients. Total cholesterol, low-density lipoprotein cholesterol and triglycerides decreased to near-optimal values in dyslipidaemia patients. CONCLUSION: This study showed that clinical pharmacy services at the HD centre can improve the management of complications in CKD patients.

Clinical pharmacy services in an Iranian teaching hospital: a descriptive study.

OBJECTIVE: To understand the types of services provided by Iranian clinical pharmacists in nephrology and infectious disease wards, the acceptance rate of clinical pharmacy services in these wards by physicians and the clinical significance of these services in the main teaching hospital in Iran. SETTING: Nephrology and infectious disease departments of a university hospital in Iran. METHODS: During a 12-month prospective data gathering phase, details of all clinical pharmacy services in the nephrology and infectious disease wards of a large university hospital were recorded in the pharmacotherapy monitoring forms. Significance impact of clinical pharmacists' services was assessed according to the guidelines of The Society of Hospital Pharmacists of Australia. MAIN OUTCOME MEASURE: Number and type of services provided. RESULTS: During 1 year, clinical pharmacists contributed to 1,386 services for 1,105 patients who were admitted in these two wards; of these services, about 95% were accepted by the physicians and about half of them were of moderate-to-life saving clinical significance. Also at least 32% of services were considered to reduce the cost of drug therapy. CONCLUSIONS: These results support the importance of clinical pharmacists' participation in health care team rounds to improve the overall quality of medication therapy, enhance patient care and outcome and reduce drug costs to patients and society.