Competitive Adsorption of a Monoclonal Antibody and Nonionic Surfactant at the PDMS/Water Interface.

Interfacial adsorption of monoclonal antibodies (mAbs) can cause structural deformation and induce undesired aggregation and precipitation. Nonionic surfactants are often added to reduce interfacial adsorption of mAbs which may occur during manufacturing, storage, and/or administration. As mAbs are commonly manufactured into ready-to-use syringes coated with silicone oil to improve lubrication, it is important to understand how an mAb, nonionic surfactant, and silicone oil interact at the oil/water interface. In this work, we have coated a polydimethylsiloxane (PDMS) nanofilm onto an optically flat silicon substrate to facilitate the measurements of adsorption of a model mAb, COE-3, and a commercial nonionic surfactant, polysorbate 80 (PS-80), at the siliconized PDMS/water interface using spectroscopic ellipsometry and neutron reflection. Compared to the uncoated SiO2 surface (mimicking glass), COE-3 adsorption to the PDMS surface was substantially reduced, and the adsorbed layer was characterized by the dense but thin inner layer of 16 Å and an outer diffuse layer of 20 Å, indicating structural deformation. When PS-80 was exposed to the pre-adsorbed COE-3 surface, it removed 60 wt % of COE-3 and formed a co-adsorbed layer with a similar total thickness of 36 Å. When PS-80 was injected first or as a mixture with COE-3, it completely prevented COE-3 adsorption. These findings reveal the hydrophobic nature of the PDMS surface and confirm the inhibitory role of the nonionic surfactant in preventing COE-3 adsorption at the PDMS/water interface.

Bioactive PLGA-curcumin microparticle-embedded chitosan scaffold: in vitro and in vivo evaluation.

Wound healing is a complex process affected by several factors. In the present work, novel biocompatible PLGA-curcumin microparticle-embedded chitosan scaffold was fabricated for wound-healing application. Process variables involved in the preparation of microparticles were optimized using design of experiment. Scanning electron microscopy (SEM) confirmed the porous nature of scaffold with embedded microparticles. A maximum release of 14% of the encapsulated curcumin was observed at 12th hour. Modified tube dilution method showed that scaffold significantly (p < 0.05) reduced multiplication of Staphylococcus aureus. More than 50% of the excised wound in rats healed in 4 days with an epithilization period of 18 days.

Chondroitinase: A promising therapeutic enzyme.

Even after 20 years of granting orphan status for chondroitinase by US FDA, there is no visible outcome in terms of clinical use. The reasons are many. One of them could be lack of awareness regarding the biological application of the enzyme. The biological activity of chondroitinase is due to its ability to act on chondroitin sulfate proteoglycans (CSPGs). CSPGs are needed for normal functioning of the body. An increase or decrease in the level of CSPGs results in various pathological conditions. Chondroitinase is useful in conditions where there is an increase in the level of CSPGs, namely spinal cord injury, vitreous attachment and cancer. Over the last decade, various animal studies showed that chondroitinase could be a good drug candidate. Research focusing on developing a suitable carrier system for delivering chondroitinase needs to be carried out so that pharmacological activity observed in vitro and preclinical studies could be translated to clinical use. Further studies on distribution of chondroitinase as well need to be focused so that chondroitinase with desired attributes could be discovered. The present review article discusses about various biological applications of chondroitinase, drug delivery systems to deliver the enzyme and distribution of chondroitinase among microbes.

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments.

CONTEXT: Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes. OBJECTIVE: To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN). MATERIALS AND METHODS: In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer. RESULTS AND DISCUSSION: The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release. CONCLUSION: This implant could be further evaluated for pharmacological activities.

Antiapoptotic Bcl-2 protein as a potential target for cancer therapy: A mini review.

Bcl-2, an antiapoptotic protein, is considered as a potential target in cancer treatment since its oncogenic potential has been proven and is well documented. Antisense technology and RNA interference (RNAi) have been used to reduce the expression of the Bcl-2 gene in many types of cancer cells and are effective as adjuvant therapy along with the chemotherapeutic agents. The lack of appropriate delivery systems is considered to be the main hurdle associated with the RNAi. In this review, we discuss the antiapoptotic Bcl-2 protein, its oncogenic potential, and various approaches utilized to target Bcl-2 including suitable delivery systems employed for successful delivery of siRNA.

Polycaprolactone-based in situ implant containing curcumin-PLGA nanoparticles prepared using the multivariate technique.

Studies on the effect of curcumin/PLGA ratio (CPR), stabilizer (PVA) concentration, homogenization speed, homogenization time, and sonication time on mean particle size (MPS) and percentage drug encapsulation (PDE) were performed using the multivariate technique. MPS and PDE were found to be more dependent on the interaction of sonication time with the other variables. Curcumin was released in a sustained manner from curcumin-PLGA nanoparticles (CPN). CPN improved the survival rate of Ehrlich ascites carcinoma (EAC)-bearing mice and controlled the EAC-induced change in hematological parameters. Histopathology of vital organs showed that the formulation was safe. Polycaprolactone was used in preparing an in situ implant containing CPN.

In vitro biocompatibility and release of curcumin from curcumin microcomplex-loaded chitosan scaffold.

CONTEXT: Scaffold if suitably modified could be used as a drug delivery system. OBJECTIVE: To develop chitosan scaffold as a delivery system for delivering curcumin in wound-healing application. MATERIALS AND METHODS: Chitosan-curcumin microcomplex particles were prepared, and the effect of drug-polymer ratio (DPR) and homogenisation speed (HS) was studied using a two-level full-factorial design. Chitosan scaffold was prepared and incorporated with curcumin microcomplexes to obtain a chitosan scaffold-containing chitosan-curcumin microcomplex (CS-CCM). Antimicrobial property of the CS-CCM against Escherichia coli was studied. The cytotoxicity of CS-CCM was studied by assessing the cell viability by MTT assay. RESULTS AND DISCUSSION: DPR had a significant effect (p ≤ 0.05) on the drug content. CS-CCM was able to inhibit the growth of E. coli considerably. The MTT results showed that CS-CCM is non-cytotoxic and supports cell proliferation. CONCLUSION: CS-CCM due to its biocompatibility and antimicrobial property could be further evaluated for potential application in wound healing.

A review on response of immune system in spinal cord injury and therapeutic agents useful in treatment.

Every year more than 12,000 people in US alone suffer from spinal cord injury. However, complete recovery of physical function is difficult due to multiple factors involved in disease progression. Currently available therapeutic regimens do not address all the factors concerned with the disease progression. The present review focuses mainly on the role of immune cells in progression of spinal cord injury and the drugs that target these immune cells. Literature search shows that inflammatory reactions and subsequent reactions that follow direct injury to spinal cord are sometimes responsible for the severity of the disease. Therefore, for design of proper treatment regimen a deep understanding in this area is required. Understanding the pathophysiology will help in creating delivery system that can target multiple factors involved in progression of spinal cord injury. A combination of various treatment strategies is required to reduce the disability in patients with spinal cord injury.

Strategies for drug delivery to the central nervous system by systemic route.

CONTEXT: Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems. OBJECTIVE: This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. MATERIALS AND METHODS: Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. RESULTS: There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. CONCLUSION: The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

Application of experimental design in preparation of nanoliposomes containing hyaluronidase.

Hyaluronidase is an enzyme that catalyzes breakdown of hyaluronic acid. This property is utilized for hypodermoclysis and for treating extravasation injury. Hyaluronidase is further studied for possible application as an adjuvant for increasing the efficacy of other drugs. Development of suitable carrier system for hyaluronidase would help in coadministration of other drugs. In the present study, the hyaluronidase was encapsulated in liposomes. The effect of variables, namely, phosphatidylcholine (PC), cholesterol, temperature during film formation (T 1), and speed of rotation of the flask during film formation (SPR) on percentage of protein encapsulation, was first analyzed using factorial design. The study showed that level of phosphatidylcholine had the maximum effect on the outcome. The effect of interaction of PC and SPR required for preparation of nanoliposomes was identified by central composite design (CCD). The dependent variables were percentage protein encapsulation, particle size, and zeta potential. The study showed that ideal conditions for production of hyaluronidase loaded nanoliposomes are PC-140 mg and cholesterol 1/5th of PC when the SPR is 150 rpm and T 1 is 50°C.