Pulmonary delivery of antitubercular drugs using spray-dried lipid-polymer hybrid nanoparticles.

The present study aimed to develop lipid-polymer hybrid nanoparticles (LPNs) for the combined pulmonary delivery of isoniazid (INH) and ciprofloxacin hydrochloride (CIP HCl). Drug-loaded LPNs were prepared by the double-emulsification solvent evaporation method using the three-factor three-level Box-Behnken design. The optimized formulation had a size of 111.81 ± 1.2 nm, PDI of 0.189 ± 1.4, and PDE of 63.64 ± 2.12% for INH-loaded LPN, and a size of 172.23 ± 2.31 nm, PDI of 0.169 ± 1.23, and PDE of 68.49 ± 2.54% for CIP HCl-loaded LPN. Drug release was found to be sustained and controlled at lower pH and followed the Peppas model. The in vitro uptake study in alveolar macrophage (AM) showed that uptake of the drugs was increased significantly if administered in the form of LPN. The stability study proved the applications of adding PLGA in LPN as the polymeric core, which leads to a much more stable product as compared to other novel drug delivery systems. Spray drying was done to produce an inhalable, dry, powdered form of drug-loaded LPN. The spray-dried (SD) powder was equally capable of producing nano-aggregates having morphology, density, flowability and reconstitutibility in the range ideal for inhaled drug delivery. The nano aggregates produced by spray drying manifested their aerosolization efficiency in terms of the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter. The in vivo study using pharmacokinetic and pharmacodynamic approaches revealed that maximum internalization efficiency was achieved by delivering LPN in SD powdered forms by pulmonary route.

Stimuli-responsive hydrogels in drug delivery and tissue engineering.

Hydrogels are the three-dimensional network structures obtained from a class of synthetic or natural polymers which can absorb and retain a significant amount of water. Hydrogels are one of the most studied classes of polymer-based controlled drug release. These have attracted considerable attention in biochemical and biomedical fields because of their characteristics, such as swelling in aqueous medium, biocompatibility, pH and temperature sensitivity or sensitivity towards other stimuli, which can be utilized for their controlled zero-order release. The hydrogels are expected to explore new generation of self-regulated delivery system having a wide array of desirable properties. This review highlights the exciting opportunities and challenges in the area of hydrogels. Here, we review different literatures on stimuli-sensitive hydrogels, such as role of temperature, electric potential, pH and ionic strength to control the release of drug from hydrogels.

Stimuli-sensitive systems--an emerging delivery system for drugs.

OBJECTIVES: Development of controlled and sustained drug delivery system (DDS) remains a great thrust of human beings for the successful delivery of drugs due to various drawbacks of existing systems. In order to overcome these drawbacks, various stimuli-sensitive DDSs were developed in the recent years. KEY FINDINGS: Stimuli are a state of responsiveness to sensory stimulation or excitability. Stimuli sensitive systems are those systems which deal with the changes in the physiology of body with respective to the environment changes. These systems may be very beneficial for the controlled and sustained delivery of drug in the body if proper work would be carried out on these types of systems. Controlled drug delivery became the standard criteria in modern pharmaceutical product design and an intensive research is still going on in achieving much better drug product with features like effectiveness, reliability, and safety. Many changes like photo and light, temperature, pH, ion, glucose, and redox affect the release of drug from the delivery system. These stimuli-sensitive systems are used for various purposes in various forms like in parenteral, ocular, peroral, rectal, vaginal, nasal, dermal and transdermal drug delivery. SUMMARY: Various literature surveys revealed that stimuli-sensitive DDSs can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional techniques.

DEVELOPMENT AND CHARACTERIZATION OF GLUCOSE SENSITIVE HYDROGELS FOR THE TREATMENT OF DIABETES MELLIT.

Development of stimuli-sensitive hydrogels for the delivery of drug involves the development of matrices that are glucose-sensitive and have strong sensing properties so that the developed system can sense the level of glucose and release the medicament in response to blood glucose level. In the present study an attempt has been made to develop a glucose sensitive hydrogel system which modulates the release of an anti-diabetic drug in response to the blood glucose level in the body. The hydrogel system was prepared by gas foaming technique using chitosan and polyvinyl alcohol (PVA) as polymer and glutaraldehyde as cross-linking agent. Metformin was used as a drug candidate because of its short biological half life (6.25±0.5 hrs). The prepared glucose sensitive hydrogel system has characterized using different parameters. It was observed that hydrogel swelled and deswelled reversibly depending on the pH and glucose sensitivity of the medium and has suitable mechanical properties. In-vitro results showed that the enzymatically immobilized hydrogel was sensitive to both pH and glucose for effective release of drug. It was found that higher the concentration of glucose in the medium, higher the amount of drug released from the hydrogel. In vivo results showed that glucose oxidase leads to reduction in blood glucose level in response to variable glucose concentration in the body thus achieving the desired therapeutic levels in the body . The present study showed that glucose sensitive hydrogels not only are efficient in controlling the physiological blood glucose level but also provide for a sustained and controlled release of drugs having short biological half life.

Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether.

The present study aimed to develop a kinetically stable nanoemulsion of artemether with improved solubility, stability and oral bioavailability. Nanoemulsion was prepared by ultrasonication technique using internal oil phase (consisted of the drug dissolved in coconut oil and span 80) and external phase (comprising tween 80 and ethanol dissolved in water). The formulations were optimized using various parameters like percentage transmittance, refractive index, drug content, viscosity, zeta potential and release rate. Stability studies were conducted for a period of 90 days using stability chambers. In vivo studies of the developed formulations were conducted on Wistar rats and data were analyzed statistically. The nanoemulsion as observed under transmission electron microscope were found to be spherical in shape with an average size of 79.0 nm and a zeta potential of -15 mV which indicated of good electrokinetic stability of nanoemulsion . Nanoemulsion was found to be clear and transparent in appearance with a percentage transmittance of 98.2. Refractive index of 1.32 of the nanoemulsion indicated the isotropic nature of the drug. Release rate of the drug from the nanoemulsion formulation was found to be quite significant (P < 0.001) as compared to the plain drug. In vivo oral bioavailability of the nanoemulsion formulation was found to be 2.6-fold higher than the plain drug (˜ 40%) as observed from pharmacokinetic studies. Thus it was observed that nanoemulsion proved itself as a promising alternate for improving the bioavailability of artemether.