Development of Mucoadhesive Gel Microbicide to Target Mucosal HIV Reservoirs

The wide use of microbicide is mainly depends on its effectiveness, less frequent application, ready availability and most importantly cost. The aim of this work was to develop affordable microbicide mucoadhesive gel formulation of synthetic anti HIV drug, stavudine and to characterise it in terms of its physical properties, mucoadhesiveness and spreadability. The purpose of the present study was also to compare different dissolution media used for in vitro release of vaginal dosage form. The gels were tested for antimicrobial, spermicidal and anti-HIV activity. Gels prepared using Carbopols and Polycarbophil were transparent and homogenous and had excellent mucoadhesion index - and showed fast drug release profile. Gels showed very good antimicrobial action against pathological microorganism

Cancer research and therapy: Where are we today?

Till date scientists are struggling to understand the complete mechanism of carcinogenesis. In future, the real time detection of cancer may help scientists to identify some of the complicated biological mechanisms. Certain special features of cancer cells enable researchers to deliver the drug or to develop the right drug therapy. These cell properties include over expression or over activity in uptake of certain nutrients e.g. folic acid and increased permeability. Listed properties might vary depending upon the type of cancer and can be fully exploited by using nanoparticles either to detect the site of cancer or to direct the drug at the affected site. Product approach like drug conjugates, complexes serves as a good platform to solve issues like solubility, toxicity, poor penetration and stability related to cancer drugs. Beside this, several drug delivery platforms are under development by researchers in academia as well as in industry to deliver therapeutic molecules and new chemical entities to the targeted site in body. Amongst them, nanotechnology both at molecular and supramolecular level is a leading platform and can help to image, detect and treat cancer. Surface modification of nanoparticles by coating or anchoring their surface with special markers, materials, peptide, proteins, antibodies or antigens add extra feature and thereby can enhance the effectiveness. These treatments can be used individually or in combined form. In this review, advances on nanotechnological platform are discussed together with some assisting techniques like magnetic field, photo or light field, sonic rays are touched upon. New biological therapies that are advancing in this direction include the antisense therapy, cell therapy, gene therapy, radiation therapy and SiRNA interfaces which are discussed in brief in this article. This article gives short overview on use of complementary and alternative medicine for treatment of cancer such as traditional Chinese medicine (TCM), Ayurveda to avoid toxic effects of synthetic drugs

present status of nanoparticle research for treatment of tuberculosis

Nanotechnology has offered enormous improvement in field of therapeutics by means of designing of drug delivery systems and opened the possibility of controlling infections at the molecular level. Nanocarriers can cross biological barriers and are able to target cellular reservoirs of Mycobacterium tuberculosis (M. tuberculosis). Nanoparticle-based systems have significant potential for treatment and prevention of tuberculosis (TB). A variety of nanocarriers have been widely evaluated as potential drug delivery systems for various administration routes. Targeting the drugs to certain physiological sites such as the lymph nodes has emerged as a promising strategy in treating TB with improved drug bioavailability and reduction of the dosing frequency. Nanotechnology based rational targeting may improve therapeutic success by limiting adverse drug effects and requiring less frequent administration regimes, ultimately resulting in more patients compliance and thus attain higher adherence levels. The development of nanoparticle based aerosol vaccine is undergoing which could serve as new platform for immunization. Present article compiles the general physiological aspects of the infection along with the relevance nanocarriers used in prevention of tuberculosi

20 years of lipid nanoparticles (SLN & NLC): present state of development & industrial applications

In 1990, the lipid nanoparticles were invented in the laboratories, the first patent filings took place in 1991. The lipid nanoparticles were developed as alternative to traditional carriers such as polymeric nanoparticles and liposomes. After 20 years of lipid nanoparticles, the present state of development is reviewed - academic progress but also the development state of pharmaceutical products for the benefit of patients. Meanwhile many research groups are active worldwide, their results are reviewed which cover many different administration routes: dermal and mucosal, oral, intravenous/ parenteral, pulmonary but also ocular. The lipid nanoparticles are also used for peptide/protein delivery, in gene therapy and various miscellaneous applications (e.g. vaccines). The questions of large scale production ability, accepted regulatory status of excipients, and - important for the public perception - lack of nanotoxicity are discussed, important pre-requisites for the use of each nanocarrier in products. Identical to the liposomes, the lipid nanoparticles entered first the cosmetic market, product examples are presented. Presently the pharmaceutical product development focuses on products for unmet needs and on niche products with lower development costs (e.g. ocular delivery), which can be realized also by smaller companies. A pharmaceutical perspective for the future is given, but also outlined the opportunities for non-pharmaceutical use, e.g. in nutraceuticals

Enhanced intraperitoneal delivery of charged, aerosolized curcumin nanoparticles by electrostatic precipitation

Aims: To investigate the potential of curcumin-loaded polylactic-co-glycolic acid nanoparticles (CUR-PLGA-NPs), alone and with electrostatic precipitation, for improving tissue uptake during pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods: Positively and negatively charged CUR-PLGA-NPs were delivered as PIPAC into inverted bovine urinary bladders ex vivo. The experiment was repeated with the additional use of electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (electrostatic PIPAC). Results: Positively charged CUR-PLGA-NPs increased depth of tissue penetration by 81.5% and tissue concentration by 80%. Electrostatic precipitation further improved the uptake of positively charged CUR-PLGA-NPs by 41.8%. Conclusion: The combination of positive charge and electrostatic precipitation have significant potential to improve tissue uptake of nanoparticles during intraperitoneal chemotherapy

Formulation development and in vitro evaluation of didanosine-loaded nanostructured lipid carriers for the potential treatment of AIDS dementia complex

The purpose of this article was to investigate the feasibility of incorporating didanosine (DDI) into nanostructured lipid carriers (NLC) for potential treatment of AIDS dementia complex. Aqueous DDI-free and DDI-loaded NLC were manufactured using hot high-pressure homogenization. The lipid matrix contained a mixture of Precirol ® ATO 5 and Transcutol ® HP. Photon correlation spectroscopy revealed that the mean particle size for all formulations was below 250 nm with narrow polydispersity indices. In addition, the d99% values for all formulations determined using laser diffractometry were below 400 nm with the span values ranging from 0.84 to 1.0. The zeta potential values ranged from −18.4 to −11.4 mV and the encapsulation efficiency of NLC for DDI ranged from 33.02% to 78.34%. These parameters remained relatively constant for all formulations tested following storage for 2 months at 25°C indicating that all the formulations were relatively stable. Differential scanning calorimetry revealed a decrease in the degree of crystallinity of NLC in all formulations developed relative to the bulk lipid material. In addition, wide-angle X-ray scattering showed that NLC in all formulations tested existed in a single β-modification form and that DDI that had been incorporated into the NLC appeared to be molecularly dispersed in the lipid matrices. Images of the NLC formulations obtained using transmission electron microscopy revealed that all formulations contained a mixture of spherical and nonspherical particles irrespective of the amount of DDI that was added during the manufacture of the formulations

Preparation, Characterization and Cell Based Delivery of Stavudine Surface Modified Lipid Nanoparticles

Previously it was shown that uncoated lipid nanoparticles of stavudine proved effective in targeting HIV viral sites in body. Therefore, the main objective of this work was to prepare and characterize surface modified stavudine entrapped lipid nanoparticles as potential drug delivery system for anti-HIV chemotherapy. The physical, targeting potential (both in vitro and in vivo) and toxicological evaluation was performed on developed nanocarriers. The degree of targeting and cellular uptake demonstrated differences among the surface coated lipid nanoparticles. We found that developed lipid nanoparticles are easy to prepare using high pressure homogenization, and has excellent stability at room temperature and refrigeration condition. In future, developed surface modified lipid nanoparticles can be evaluated clinically

PREPARATION AND CHARACTERIZATION OF STAVUDINE ENTRAPPED LIPOSPHERES

Lipospheres  of  stavudine  were  prepared  by  melt  dispersion technique  using  trimyristin,  tripalmitin and  triastearin,  stearic acid, Compritol®  888  ATO  and  Precirol®  ATO  5  as  lipid  matrix  in  the various  drug-lipid  ratios.  Drug  entrapped  free  flowing  solid lipospheres  of  triglycerides  and  glyceryl  behenate  were characterized  for  surface  morphology,  particle  size  distribution, encapsulation efficiency, and in vitrorelease behavior. The effect of drug lipid ratio, the surfactant used, concentration of stabilizer, and stirring  speed  were  identified  as  the  key  variables  affecting  the formation  of  discrete  spherical  lipospheres  and  sustained  drug release  rate.  The  lipospheres  production  conditions  were  optimized by using 2% w/w sodium cholate and 1% Plural oleic as a stabilizer. The  concentration  of  lipid  used  had  pronounced  effect  on  particle size of the lipospheres. The incorporation efficiency was found to be in range of 30  to  50%. Increase  in concentration of surfactant and stirring  speed  produced  fine  spherical,  smooth,  and  round lipospheres.  All  the  prepared  lipospheres  exhibited  slow  release profiles dictating the Higuchi mode of release.Key  words: Lipospheres,  stavudine,  lipid  matrix,  hydrophilic  surfactant, drug releas

IN VIVO EVALUATION OF SUPPOCIRE PARACETAMOL RECTAL SUPPOSITORIES

To achieve successful delivery of drug locally as well as systematically rectal route has proved its potential. The main objective of this research work was to evaluate the in vivo performance of paracetamol Suppocire CP suppository. Initially, suppositories were prepared, evaluated for their physicochemical parameters and in vitro drug release. An in vivo investigation of paracetamol availability in rabbits was carried out in comparison with marketed paracetamol suppository and suspension in complete cross-over design. The comparison between the three different formulations in terms of whole blood concentration revealed that the extent of drug absorption from Suppocire suppository and marketed suppository is comparable and showed promise that product of similar characteristic can be formulated using an amphiphilic suppository base. Bioavailability study showed comparable absorption after rectal and oral administration. A rectal irritation study exhibited high irritation profile for marketed suppository to rectal mucosa as compared to Suppocire suppository which showed no irritation

Nevirapine nanosuspensions: stability, plasma compatibility and sterilization

The feasibility of preparing lyophilized or spray dried forms for reconstitution into nanosuspension (NS) was investigated in this study. The bare and surface modified aqueous NS of nevirapine were successfully converted into an anhydrous form by both techniques. The optimization of suitable cryoprotectant is essential to obtain completely dry product of desired properties. The NS adsorbed spray dried powder and granules would serve as excellent carriers for oral antiretroviral delivery. Furthermore, granules compressed to tablet showed sustained release compared to conventional marketed tablet. These results indicated that NS can be lyophilized and spray dried to prepare a product suitable for a parenteral and oral dosage form, respectively provided the formulation composition withstand phase changes during the drying processes process. Effect of sterilization method viz. steam and radiation on aqueous and lyophilized NS was also studied