Bina Gidwani

Nanostructured lipid carriers and their current application in targeted drug delivery

In the last few decades, various drug-delivery technologies have emerged and a fascinating part of this has been the development of nanoscale drug delivery devices. Nanoparticles (NPs) and other colloidal drug-delivery systems modify the kinetics, drug distribution in the body and release profile of an associated drug. Nanostructured lipid carriers (NLCs) have been reported to be an alternative system to emulsions, liposomes, microparticles, solid lipid nanoparticles (SLNs) and their polymeric counterparts due to their numerous advantages. This paper basically reviews the types of NLCs, mechanism of skin penetration, stability related issues along with their production techniques, characterisation and applications towards targeted drug delivery.

Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment

Abstract PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of AL type complex with stability constant (Ks = 645 M−1). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4 ± 2.53 nm and − 31.9 ± (−3.08) mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC50 value was found to be 4.3 ± 0.11 µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency.

Rosin: Recent advances and potential applications in novel drug delivery system

Gum exudates are among the oldest natural polymer. Natural gums have remained one of the major areas of interest for the researchers for their applicability in the drug delivery system because of their wide availability, inexpensiveness and availability in a variety of structures with varied properties. They can be easily modified chemically, biochemically and are highly stable, safe, non-toxic, gel forming and in addition are biodegradable. Rosin is one of the natural gums obtained as resinous constituent of the oleoresin exuded by various species of pine, mostly conifers. Rosin consists primarily of abietic- and pimaric-type resin acids (or rosin acids) with characteristic hydrophobic hydrophenanthrene rings which impart them excellent film-forming properties. Rosin and its derivatives are biopolymers that are increasingly used for their pharmaceutical applications. In the pharmaceutical field, it has been investigated for film-forming and coating properties, microencapsulation and as a matrix material in the tablets for sustained and controlled drug release. This article reviews the literature on rosin and its derivative and describes the varied applications of the rosin and their future exploitation in novel drug delivery systems.

Preparation, characterization, and optimization of altretamine-loaded solid lipid nanoparticles using Box-Behnken design and response surface methodology

The objective of the present study was to prepare solid lipid nanoparticles (SLNs) of altretamine (ALT) by the hot homogenization and ultrasonication method. The study was conducted using the Box-Behnken design (BBD), with a 33 design and a total of 17 experimental runs, performed in combination with response surface methodology (RSM). The SLNs were evaluated for mean particle size, entrapment efficiency, and drug-loading. The optimized formulation, with a desirability factor of 0.92, was selected and characterized. In vitro release studies showed a biphasic release pattern from the SLNs for up to 24 h. The results of % EE (93.21 ± 1.5), %DL (1.15 ± 0.6), and mean diameter of (100.6 ± 2.1) nm, were very close to the predicted values.

The potentials of nanotechnology-based drug delivery system for treatment of ovarian cancer.

Abstract Ovarian cancer is one of the leading causes for death of women. Every year the percentage of mortality rate is increasing day by day. Various chemotherapeutic agents are used to increase the survival rate of patients with ovarian cancer, but the available conventional dosage forms/marketed preparations are associated with several limitations. The use of nanotechnology in drug delivery contributes to their small size (10–100 nm), which improves the circulation and enables superior accumulation of therapeutic drugs at the tumor sites. In future, the use of nanotechnology will enable passive targeting and further improvements can be made using targeting moieties.

Pharmacokinetic study of solid-lipid-nanoparticles of altretamine complexed epichlorohydrin-β-cyclodextrin for enhanced solubility and oral bioavailability

Altretamine is a synthetic drug approved for treatment of ovarian cancer. The only drawback with its formulation is poor aqueous solubility and low oral bioavailability. In the present work an attempt has been made to prepare inclusion complex of altretamine with epichlorohydrin beta cyclodextrin. The complexes were prepared by kneading, co-evaporation and freeze-drying method and were confirmed by FTIR, XRD, DSC, drug content and dissolution study. Kneaded complex possess maximum solubilizing efficiency of 82.63 in 25mM Epi-β-CD solution. SLNs of pure altretamine and ALT complexed with Epi-β-CD were prepared by modified emulsification-ultrasonication method. The particle size and zeta potential was found to be 151.5nm and -21.3mV. The drug release pattern of SLNs was bi-phasic in nature; with an initial burst release followed by sustained drug release. Pharmacokinetic study showed that the average Cmax was found to be 0.94μg/ml, which was 2.47 times higher as compared to the pure drug. The AUCt for SLNs was 150minμgh/ml and 54minμgh/ml for pure ALT suspension which proved that the SLNs exhibited greater absorption compared to the pure drug. Thus, smaller particle size, higher entrapment efficiency and enhanced aqueous solubility led to improvement in oral bioavailability of ALT.

In vitro and in vivo evaluation of PEGylated nanoparticles of bendamustine for treatment of lung cancer

The purpose of this study was to develop PEGylated nanoparticles of bendamustine (BM) to improve therapeutic efficiency of drug and reduce the side-effects. The nanoparticles were prepared by a modified diffusion–emulsification method. The particle size and zeta potential of optimized BM-loaded PEGylated NPs were found to be 256 nm and −29.1 mV. The in vitro release showed biphasic behavior, with initial burst release followed by slow sustained delivery. The anti-tumor activity was determined using the A- 549 cell line, by the MTT assay. The stability study revealed that the nanoparticles prepared were stable for 3 months at both 25°C and 4°C.

Application of nanocarrier-based drug delivery system in treatment of oral cancer

Abstract Oral cancer includes cancer of lips, oral cavity and oropharynx. Oral cancer is the sixth most life-threatening disease affecting 65% of population. The delivery of cytotoxic chemotherapeutic anticancer drugs is a challenging task due to unfavorable properties. Both synthetic chemotherapeutic agents and herbal constituents are used in treatment of oral cancer. The purpose of present article is to overcome the limitations through concept of nanotechnology and conjugation approach. Also, it will provide better therapeutic effect and sustain long life of healthy and recovered cells. Moreover, development in this area will raise opportunities for the oncologist, researchers and pharmaceutical scientists. This review summarizes the clinical findings and patents on various oral anticancer drugs for effective pharmacotherapeutics.

Formulation and evaluation of gel containing nanostructured lipid carriers of tretinoin–Epi-β-CD binary complex for topical delivery

The objective of present research work was to formulate and evaluate topical gel containing tretinoin–cyclodextrin (CD) binary complex loaded into nanostructured lipid carriers (NLCs). Use of cyclodextrin and nanolipid carrier together in a system produced a synergistic effect by increasing the drug release and skin permeation, thus improving the overall therapeutic effect. Two different cyclodextrins i.e. β-CD and its water soluble polymeric derivative epichlorohydrin-β-cyclodextrin (EPI-β-CD) were used to obtain binary inclusion complex of drug-cyclodextrin (D-CD) systems by two different techniques (kneading and co-evaporation). The prepared solid complexes were characterized by FTIR, DSC, XRD etc. and the best system was selected for loading into nanolipid carriers. NLC comprising glyceryl mono stearate (GMS) and oleic acid were obtained by slightly modified emulsification evaporation method. Four different formulations of NLCs were suitability characterized for particle size, zeta potential, entrapment efficiency, drug loading and drug release. EPI-β-CD was found to be more effective than β-CD in enhancing solubility and dissolution properties of tretinoin. The most effective NLC formulation was incorporated into carbopol hydrogel which showed better permeation properties than that of the reference gel (0.1%).

Factorial Design and a Practical Approach for Gastro-Retentive Drug Delivery System

Over the years, different formulation technologies intended for gastro retentive dosage delivery were investigated and patented. Oral drug administration has been the predominant route for drug delivery. During the past two decades, numerous oral delivery systems have been developed to act as drug reservoirs from which the active substance can be released over a defined period of time at a predetermined and controlled rate. From a pharmacokinetic point of view, the ideal sustained and controlled release dosage form should be comparable with an intravenous infusion, which supplies continuously the amount of drug needed to maintain constant plasma levels once the steady state is reached. Although some important applications, including oral administration of peptide and protein drugs, can be used to prepare colonic drug delivery systems, targeting drugs to the colon by the oral route. This review article clearly explains the advantages, limitations and need of gastro-retentive drug delivery system. It also covers the various criteria for drugs suitable and not suitable for such delivery. Also, the different types of gastro retentive delivery systems are described with suitable examples.