Journal: Current drug delivery
The present investigation was carried out to formulate and optimize the bioerodable insert of Azithromycin in order to prolong the release time and improve the ocular availability in ophthalmic infections. A modified solvent casting method was used for the preparation of azithromycin insert in which hydroxyl propyl methyl cellulose (HPMC) and Eudragit RL100 were used as drug reservoir and rate controlling membrane respectively. Thereafter the, formulations were evaluated for the uniformity of thickness and weight, surface pH, folding endurance, percentage moisture loss, percentage moisture absorption, drug content, in-vitro release, kinetics studies (zero order, first order, Higuchi and Korsmeyer - Peppas model) and stability studies. The Formulation H8 (amongst the range of H1-H10) ,comprising of 1.5% HPMC and 3% Eudragit RL100 ,was found to be optimized formulation on the basis of uniformity of thickness (0.26 ± 0.004 mm) and weight (24.9 ± 0.27 mg), surface pH (7.1 ± 0.063), folding endurance (18.3 ± 0.81), percentage moisture loss (7.49 ± 0.30%), percentage moisture absorption (5.7%), drug content (1.98 mg ), in-vitro release (99%) , stability studies (Shelf life- 346 days) and better ocular tolerability. The formulation H8 showed a steady and controlled release of the drug over a 12 hour period with non-Fickian diffusion release mechanism, compared to a normal release period of 2-3 hours. The optimized insert showed promising results and can be used to treat a wide range of ocular infections.
Dermal application of various active substances is widely preferred for topical or systemic delivery. SLNs are consisting of biocompatible and non-toxic lipids and have a great potential for topical application of drugs. In this study, semisolid SLN formulations were successfully prepared by a novel one-step production method as a topical delivery system of an anti-inflammatory drug, etofenamate. Compritol 888 ATO and Precirol ATO 5 were chosen as lipid materials for the fabrication of the formulations. In-vitro evaluation of the formulations was performed in terms of encapsulation efficiency, particle size, surface charge, thermal behavior, rheological characteristics, in vitro drug release profile, kinetics, mechanisms, stability, and anti-inflammatory activity. The colloidal size and spherical shape of the particles were proved. According to the results of rheological analysis, it was demonstrated that the semisolid SLN formulations have a gel-like structure. Stability studies showed that semisolid SLNs were stable at 4°C for six months period. Zero order release was obtained with Precirol ATO 5, while Compritol 888 ATO followed square root of time (Higuchi’s pattern) dependent release. Semisolid SLNs were shown higher inhibitory activity of COX in comparison with pure etofenamate. In conclusion, etofenamate loaded semisolid SLN formulations can be successfully prepared in a novel one-step production method and promised their use for topical application.
The objective of the present study was to prepare taste-masked mini-tablets, which are easily swallowed dosage forms primarily used by pediatric and geriatric patients. Hot-melt extrusion technology was used to prepare mini-tablets of the bitter model drug ketoprofen. Eudragit® EPO was used as a taste-masking polymer for the mini-tablets. Thermo gravimetric analysis studies showed that the drug was thermally stable under the employed extrusion parameters. Differential scanning calorimetry and polarized light microscopy-hot stage microscopy studies confirmed that the binary mixtures were miscible under the employed extrusion temperatures. The binary mixtures (10%-50% w/w) were blended and extruded with a 5-mm strand die and cut into consistent mini-tablets by using an adapted downstream pelletizer.In vitro release studies showed that drug release was less than 0.5% within the first 2 min in simulated salivary fluid (pH 6.8) and more than 90% in the first 20 min in gastric media (pH 1.0). The results of the electronic tongue analysis were well correlated with the drug release results obtained for the mini-tablets in artificial saliva. SEM revealed no pores or cracks on the surface of the mini-tablets, confirming that the mini-tablets were compact solids. Fourier transform infrared studies revealed that the carboxylic acid group in ketoprofen had an intermolecular interaction with the carrier. Chemical imaging confirmed the uniform distribution of ketoprofen inside the polymer matrices. These results confirmed the excellent suitability of Eudragit® EPO for the preparation of novel pediatric and geriatric dosage forms aimed at masking drug taste and improving patient compliance.
Salbutamol sulphate (SS) is a model short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm having poor bioavailability (50%) due to its extensive first-pass effect.
Curcumin is a yellow polyphenolic chemopreventive agent isolated from the rhizomes of Curcuma longa. It is approved as Generally Regarded As Safe by US FDA. Nonetheless, its clinical success is limited due to its poor aqueous solubility, fast metabolism and short biological half-life attributes. Quercetin-decorated liposomes of curcumin (QCunp) are perceived to be able to negate these drawbacks. The QCunp and Cunp were prepared by lipid hydration technique. Their particle size, zeta potential, surface morphology, drug loading and release characteristics were examined. The efficacy and toxicity of curcumin liposomes with and without quercetin were evaluated in-vitro against the HT-29 and HCT-15 cancer cell lines. The curcumin liposome variants were also challenged against Dalton’s ascites lymphoma in mice. QCunp were more effective in increasing the life span and body weight of lymphoma inflicted mice compared to Cunp. QCunp treatment showed significant efficacy improvement both in case of in-vitro cell line and in-vivo animal studies. QCunp exhibit promising potential to emerge as alternative anti-cancer therapeutics.
Nanotechnology has provided substantial benefits in drug delivery, especially in the treatment of dermatological diseases. Psoriasis is a chronic inflammatory skin disease in which topical delivery of antipsoriatic agents is considered the first line treatment.
Bacteriophage (from ‘bacteria’ and Greek φαγεῖν phagein “to devour” or bacterial eaters) are bacterial viruses that infect and kill bacteria. Bacteriophages (shortly “phages”) are among the most common and diverse entities in the biosphere. The estimated number of phages on earth is about 1032. Bacteriophages are often isolated from environmental sources, such as water samples, etc. Felix d'Herelle - one of the discoverers of bacteriophages was the one who suggested them for therapy of human and animal bacterial infections. This idea was very popular in the world until the advent of antibiotics commercial after which production of therapeutic phages ceased in most of the Western countries, but not in the former Soviet Union. The application of antibiotics in the clinical practice, besides the well-known side effects, entails, in addition, the appearance of the forms of bacteria, resistant to newly synthesized preparations. It was concludes that a European and global strategy to address this gap is urgently needed. Now, faced with the alarming growth of variety of antibiotic resistant bacterial infections, Western researchers and governments are giving phages a serious look. The phages nowadays are seen as a possible therapy against multi-drug-resistant strains of many bacteria. The therapeutic action of bacteriophages significantly differs from antibiotics which makes them still active against multi-drug-resistant bacteria. Bacteriophages have a number of other advantages in comparison with antibiotics, first of all they are efficient against multi-drug-resistant bacteria. The aim of this review was to provide an overview of the past and current experiences in the field of phage therapy in the countries where it has been traditionally applied in clinical practice. Although the style and quality of old Soviet scientific publications dedicated to phage therapy are not challenging the international standards, there is still valuable information which may not be neglected by modern researchers. This information is especially important as it remained unavailable for the Western scientists before because of the language barriers up until now. The goal of this articles is to encourage further research on this topic, facilitate rapid decisions on development of appropriate regulations, which would ultimately permit using phages as therapeutic or preventative medicines in daily clinical practice in Western countries where multiply drug-resistant bacteria gradually becomes the greatest life threatening problem.
With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy.
Oral administration of medication is the first option when patient compliance is considered. However, many barriers face oral absorption of drugs that limit bioavailability in about 90% of therapeutic agents. Utilization of nanoparticulate drug delivery systems is a major strategy for increasing oral absorption. They can improve oral bioavailability through mechanisms such as protection of the drug in the GI tract, increasing cellular contact and residence time of the drug, protection of the drug from pre-systemic metabolism and efflux and increasing diffusion across the mucosal and epithelial layers. Liposomes are biocompatible carriers employed to improve oral bioavailability of drugs and in addition to the general advantages of nanocarriers for oral delivery, they offer benefits derived from their lipidic bilayer structure. They can better adhere to biomembranes, form mixed-micelle structures with bile salts to increase the solubility of poorly-soluble drugs and are suitable candidates for lymphatic uptake. They have been successful in improving oral bioavailability of a variety of compounds including peptide and proteins, hydrophilic and lipophilic drugs. Stability under GI conditions is the main concern for oral liposomes, however, promising approaches have been suggested to increase the stability of oral liposomes. These include: using appropriate lipid compositions, polymer coating, addition of stabilizing lipids to liposomal structures, preparation of double liposomes and proliposomes and some other innovative methods. The present review focuses on the role of liposomes in improving oral absorption of drugs, the problems encountered, and the types of liposomes designed to overcome these issues. Barriers to oral delivery will be discussed and examples of bioavailability enhancement upon encapsulation in various types of liposomes investigated.
Nowadays, cancer hyperthermia is attracting much attention in basic science and clinics. Among the hyperthermia techniques, microwave (MW) heating is most commonly used for cancer treatment. It offers highly competitive advantages: faster heat generation from microwave radiation, less susceptibility to heat up local tissues, maneuverability, and depth of penetration in tissues and capability of killing tumor cells. Although the encouraging clinical results are being collected, MW hyperthermia has its own challenges, such as inaccurate targeting, low selectivity, which leads to damage to surrounding vital organs and tissues. To address these issues, micro-nano materials have emerged as a promising agent as the receiver of the electromagnetic wave, which should be beneficial for improving the efficacy of MW hyperthermia. Here, we review the most recent literature on micro/nanomaterials-based MW heating strategies for treatment of cancer, with the aim to give the reader an overview of the state-of-the-art of MW hyperthermia therapy. The future of MW responsive materials will also be discussed, including combination of imaging probes and targeting moieties.