Upendra Nagaich

Mesoporous silica nanoparticles in target drug delivery system: A review

Due to lack of specification and solubility of drug molecules, patients have to take high doses of the drug to achieve the desired therapeutic effects for the treatment of diseases. To solve these problems, there are various drug carriers present in the pharmaceuticals, which can used to deliver therapeutic agents to the target site in the body. Mesoporous silica materials become known as a promising candidate that can overcome above problems and produce effects in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles (MSNs) are widely used as a delivery reagent because silica possesses favorable chemical properties, thermal stability, and biocompatibility. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release of the target site. The properties of mesoporous, including pore size, high drug loading, and porosity as well as the surface properties, can be altered depending on additives used to prepare MSNs. Active surface enables functionalization to changed surface properties and link therapeutic molecules. They are used as widely in the field of diagnosis, target drug delivery, bio-sensing, cellular uptake, etc., in the bio-medical field. This review aims to present the state of knowledge of silica containing mesoporous nanoparticles and specific application in various biomedical fields.

Nanoparticles laden in situ gelling system for ocular drug targeting

Designing an ophthalmic drug delivery system is one of the most difficult challenges for the researchers. The anatomy and physiology of eye create barriers like blinking which leads to the poor retention time and penetration of drug moiety. Some conventional ocular drug delivery systems show shortcomings such as enhanced pre-corneal elimination, high variability in efficiency, and blurred vision. To overcome these problems, several novel drug delivery systems such as liposomes, nanoparticles, hydrogels, and in situ gels have been developed. In situ-forming hydrogels are liquid upon instillation and undergo phase transition in the ocular cul-de-sac to form viscoelastic gel and this provides a response to environmental changes. In the past few years, an impressive number of novel temperature, pH, and ion-induced in situ-forming systems have been reported for sustain ophthalmic drug delivery. Each system has its own advantages and drawbacks. Thus, a combination of two drug delivery systems, i.e., nanoparticles and in situ gel, has been developed which is known as nanoparticle laden in situ gel. This review describes every aspects of this novel formulation, which present the readers an exhaustive detail and might contribute to research and development.

Intranasal delivery of chitosan nanoparticles for migraine therapy.

Objective The objective of the research was to formulate and evaluate sumatriptan succinate-loaded chitosan nanoparticles for migraine therapy in order to improve its therapeutic effect and reduce dosing frequency. Material and Methods The Taguchi method design of experiments (L9 orthogonal array) was applied to obtain the optimized formulation. The sumatriptan succinate-loaded chitosan nanoparticles (CNPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and Tween 80 as surfactant. Results The CNPs had a mean size of 306.8 ± 3.9 nm, a zeta potential of +28.79 mV, and entrapment efficiency of 75.4 ± 1.1%. The in vitro drug release of chitosan nanoparticles was evaluated in phosphate buffer saline pH 5.5 using goat nasal mucosa and found to be 76.7 ± 1.3% within 28 hours. Discussion The release of the drug from the nanoparticles was anomalous, showing non-Fickian diffusion indicating that drug release is controlled by more than one process i.e. the superposition of both phenomena, a diffusion-controlled as well as a swelling-controlled release. This is clearly due to the characteristics of chitosan which easily dissolves at low pH, thus a nasal pH range of 5.5 ± 0.5 supports it very well. The mechanism of pH-sensitive swelling involves protonation of the amine groups of chitosan at low pH. This protonation leads to chain repulsion, diffusion of protons and counter ions together with water inside the gel, and the dissociation of secondary interactions. Conclusion The results suggest that sumatriptan succinate-loaded chitosan nanoparticles are the most suitable mode of drug delivery for promising therapeutic action.

Synthesis and preliminary therapeutic evaluation of copper nanoparticles against diabetes mellitus and -induced micro- (renal) and macro-vascular (vascular endothelial and cardiovascular) abnormalities in rats

The current study synthesized and investigated the effect of low-dose copper nanoparticles (CuNPs) against diabetes mellitus (streptozotocin, 50 mg kg−1, i.p., once) and -induced experimental micro- (nephropathy) and macro-vascular (cardio and endothelium) complications. Diabetes mellitus (DM)-induced vascular abnormalities were revealed by the reduction in acetylcholine-induced endothelium-dependent relaxation, the decrease in aortic and serum nitrite/nitrate concentration, increased CKMB, LDH, SGOT/SGPT, serum creatinine, and blood urea nitrogen, and the induction of proteinuria and oxidative stress. However, treatment with low-dose CuNPs (1 mg kg−1, p.o. 4 weeks) after streptozotocin administration reduced serum glucose concentration. Moreover, CuNPs had shown a partial but significant prevention of cardio-vascular structural and functional abnormalities in diabetic rats. Increased bioavailability of NO in the endothelium and reduction in oxidative stress might be the possible mechanisms involved for the protective role of CuNPs against diabetes-induced micro- and macro-complications.

Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history.

There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to companys discovery, customers complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firms recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall.

Fabrication and in vitro evaluation of mucoadhesive ondansetron hydrochloride beads for the management of emesis in chemotherapy

Background Mucoadhesive beads were fabricated and evaluated for controlled release of an antiemetic drug ‘Ondansetron Hydrochloride’. Ondansetron hydrochloride is a serotonin 5-HT3 receptor antagonist mainly used for the treatment of emesis, which occurs as a side effect of chemotherapy. Materials and Methods: The present work was to fabricate and evaluate ondansetron-loaded microbeads by using chitosan as mucoadhesive and sustained release polymer. Sodium tripolyphosphate (Na-TPP) was used as a cross-linking agent. The microbeads were successfully prepared by ionotropic gelation technique. The particle size, entrapment efficiency, and mucoadhesive strength of drug-loaded formulations was measured by an optical microscope, direct crushing method, and in vitro wash-off method, respectively. Results: Particle size, entrapment efficiency, mucoadhesive strength, and in vitro drug release of optimized formulation was found to be 760.11 ± 1.02 μm, 75.09 ± 2.40%, 95.14 ± 0.27% and 87.45 ± 1.21%, respectively. The data was fitted to different kinetic models to illustrate its anomalous (non-Fickian) diffusion. Conclusions: The results revealed that ondansetron HCl loaded microbeads are most suitable mode of drug delivery for promising therapeutic action. Ondansetron HCl-loaded microbeads can prove to be potential pharmaceutical dosage forms for sustaining the drug release and reducing the dose frequency.

pHEMA hydrogels: Devices for ocular drug delivery

Drug delivery to eye has become a demanding task because of various constraints of eye i.e., physiological and anatomical, which results in improper therapeutic concentration at the site of action. Due to this problem, frequent dosing was recommended causing patient incompliance and adding to the cost of therapy. To overcome these barriers, researchers have discovered novel ocular delivery systems like hydrogels, ocuserts, colloidal carriers, etc. However, every delivery system has its own advantages and disadvantages. Hydrogels are presently utilized as delivery system for actives because of their comparable physical properties to that of living tissue. A plethora of biodegradable polymers are used for hydrogel formulations like polyanhydrides, poly (orthoesters), polyesters and poly (2-hydroxyethyl methacrylate) (pHEMA), chitosan and sodium alginate out of which pHEMA hydrogels are becoming popular from a therapeutic point of view for the ocular drug delivery. The present paper broadly describes the recent advances on drug delivery using pHEMA hydrogels with exhaustive details of researches explored till date.

Antioxidant and Antibacterial Potential of Silver Nanoparticles: Biogenic Synthesis Utilizing Apple Extract

The advancement of the biological production of nanoparticles using herbal extracts performs a significant role in nanotechnology discipline as it is green and does not engage harsh chemicals. The objective of the present investigation was to extract flavonoids in the mode of apple extract and synthesize its silver nanoparticles and ultimately nanoparticles loading into hydrogels. The presence of flavonoids in apple extract was characterized by preliminary testing like dil. ammonia test and confirmatory test by magnesium ribbon test. The synthesized silver nanoparticles were characterized using UV spectroscopy, particle size and surface morphology, and zeta potential. Silver nanoparticles loaded hydrogels were evaluated for physical appearance, pH, viscosity, spreadability, porosity, in vitro release, ex vivo permeation, and antibacterial (E. coli and S. aureus) and antioxidant studies (DPPH radical scavenging assay). Well dispersed silver nanoparticles below were observed in scanning electron microscope image. Hydrogels displayed in vitro release of 98.01%  ±  0.37% up to 24 h and ex vivo permeation of 98.81  ±  0.24% up to 24 h. Hydrogel effectively inhibited the growth of both microorganism indicating good antibacterial properties. The value of percent radical inhibition was 75.16%  ±  0.04 revealing its high antioxidant properties. As an outcome, it can be concluded that antioxidant and antiageing traits of flavonoids in apple extract plus biocidal feature of silver nanoparticles can be synergistically and successfully utilized in the form of hydrogel.

Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

O objetivo da pesquisa foi formular e avaliar nanoparticulas de quitosana contendo cloridrato de selegilina para terapia do Parkinson, a fim de melhorar o seu efeito terapeutico e reduzir a frequencia de dosagem. Metodo de Taguchi, de planejamento experimental, (L9 matriz ortogonal) foi usado para obter a formulacao otimizada. As nanoparticulas de quitosana contendo cloridrato de selegilina (PCHs) foram preparadas por gelificacao ionica de quitosana com ânions tripolifosfato (TPP) e Tween 80 como tensoativo. As PCHs apresentaram tamanho medio de (303.39 ± 2,01) nm, potencial zeta de +32.50 mV e eficiencia de encapsulacao de 86.200±1,38%. A liberacao do farmaco in vitro foi avaliada em solucao salina de tampao fosfato (pH 5,5), usando a mucosa nasal de cabra e o resultado encontrado foi de 82.529% ± 1.308, acima de 28 h. Estudos de cinetica de liberacao mostraram que a liberacao do farmaco das nanoparticulas foi por difusao anomala (nao fickiana), indicando que e controlada por mais de um processo, ou seja, a superposicao dos fenomenos de difusao controlada e intumescimento. As PCHs mostraram resultados de boa estabilidade, encontrada durante os estudos de estabilidade em temperaturas diferentes, como mencionado em diretrizes do ICH. Os resultados revelaram que o sistema de nanoparticulas de quitosana contendo cloridrato de selegilina e o mais adequado sistema de liberacao de farmacos de acao terapeutica promissora.

Controlled ocular drug delivery of ofloxacin using temperature modulated in situ gelling system

Background: The designing of ocular dosage form off ers complicated issues. Numerous protective mechanisms are present in the eye to prevent the absorption of drug candidate from the corneal membrane. The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome by the use of in situ gel forming systems, which are instilled as drops into the eye and then undergo a sol-gel transition in the cul-de-sac. In situ forming polymeric formulations drug delivery systems is in sol form before administration in the body, but once administered, undergoes gelation in situ to form a gel. The formulation of gel depends upon factors like temperature modulation, pH changes, presence of ions, and ultraviolet irradiation, from which drug gets released in sustained and controlled manner. Objective: The present investigation deals with formulation and evaluation of Pluronic; based in situ gel of ofloxacin. Material and Method: Pluronic as gelling agent, HPMC as viscosity modifying agent was used. Ofloxacin was used as Active Pharmaceutical Ingredient. Results: In vitro drug release studies indicated that the formulated in situ gel retained the drug better than the conventional dosage forms. The formulations were therapeutically efficacious, sterile, stable, and provided controlled release of the drug over a period of time. Conclusion: The results demonstrate that the developed system is an alternative to conventional ophthalmic drops, patient compliance, industrially-oriented, and economical.