The discovery of proteins and peptides marked the actual beginning for pharmaceutical companies to do research on novel delivery systems for delivering these therapeutic proteins. Biodegradable polymer-based microspheres for controlled-release depot injection are known for decades and have proved to be one of the best possible approaches. Despite being known for decades, the commercial success of microsphere-based delivery systems remains limited. Very few products are seen in the market with no generics available for approved brand products whose patents have either expired or are about to expire. All this points to the complexities involved in developing these delivery systems. Still, many hurdles remain in developing these drug delivery systems namely, poor drug entrapment, unwanted burst release, poor in vitro in vivo correlation, lack of proper in vitro testing methods, problems involved during scale-up, and the most important hurdle being sterilization of the product. To achieve successful product development, all of these technical difficulties need to be simultaneously dealt with and resolved. This article attempts to highlight the problem areas for these delivery systems along with the regulatory requirements involved and map the present status of these delivery systems.
Generally, therapeutic drugs have issues like poor solubility, rapid removal from the bloodstream, lack of targeting, and an inability to translocate across cell membranes. Some of these barriers can be overcome by using nano drug delivery systems (DDS), which results in more efficient drug delivery to the site of action. Due to their potential application as drug delivery systems, nanoparticles are the main topic of discussion in this article. Experimental and computational investigations have substantially aided in the understanding of how nanocarriers work and how they interact with medications, biomembranes and other biological components. This review explores how computational modelling can aid in the rational design of DDS that has been optimized and improved upon. The most commonly used simulation methods for studying DDS and some of the most important biophysical elements of DDS are also discussed. Then, we conclude by investigating the computational properties of various types of nanocarriers, such as dendrimers and dendrons, polymer-, peptide-, nucleic acid-, lipid-, carbon-based DDS, and gold nanoparticles.
Aim and Objective The primary aim of the present investigation was to adopt the concept of quality by design (QbD) for developing Febuxostat matrix tablets containing a novel combination of polyethylene oxide (PEO), pre-gelatinized starch (PGS) and lactose for obtaining biphasic drug release. Experimental work Febuxostat-containing matrix tablets were prepared by direct compression using 32 full factorial designs. The tablets were prepared with varying amounts of PEO WSR 301 to PGS and lactose to obtain the desired release pattern. The chosen responses were cumulative % drug released at 1, 6 and 12 hours. The evaluation of tablets was done for pre and post-compressional parameters. Compared with the marketed tablet, the optimized formulations were selected based on in vitro drug release. Dose dumping was checked in the dissolution medium containing up to 40% alcohol. Result and discussion The results of the dissolution study indicated that the batch containing a 1:1 ratio of PEO WSR 301 and PGS (15 mg each) and 20 mg of Lactose showed fast initial drug release to imitate the pharmacological action followed by sustained drug release effect. The use of Lactose facilitated immediate drug release, while PEO WSR 301 and PGS exhibited the opposite effect on cumulative drug release. The results of the 32 Factorial design revealed that the concentration of Lactose is a critical parameter. Dose dumping was not observed in the alcoholic dissolution medium. Kinetic equations were fitted to the dissolution data after 1 hour of the dissolution study. Conclusion The type (soluble or swellable) and the concentration of excipients (low or high) dictate the tablets' drug release. The study's outcome revealed that the most critical material attribute is the amount of lactose. The novel combination of PEO, PGS and lactose can bypass existing patents and give more industrial applicability.
Background: Gold nanoparticles have the potential to be used as a carrier in drug delivery system due to their small size, large surface area and short circulation time in blood.
Objective: This study aims that doxorubicin conjugation with gold nanoparticles (AuNPs) may reduce its toxicity as well as improve therapeutic efficacy.
Methods: Five groups of Albino rats were used; 1: healthy control, 2: Injured, 3: injured and treated with Dox, 4: Injured and treated with AuNPs, 5: Injured and treated with AuNPs: Dox. At the end of the experiment, blood and liver tissues were processed for biochemical and histopathological analysis. The expression of collagen, HO-1, IL-6 and TNF-α genes involved in liver fibrosis was observed through real-time PCR.
Results: At the end of the experiment, it was observed that the body weights of DOX treated rats decreased by 0.72%, however, AuNPs and Au: DOX treated rats were 15.3% and 29.13% respectively. The percentage of liver protection determined through alanine aminotransferase and aspartate aminotransferase levels in DOX, AuNPs and AuNPs: DOX treated groups were 39.21%, 79.26%, 98.17% and 47.77%, 84.17%, 97.92% respectively. That represents better recovering liver in Dox-AuNPs treated rats compared to others. Histopathological and gene expression studies further support the findings. The mRNA expression levels of inflammatory and oxidative stress related genes HO-1, IL-6 and TNF-α were upregulated in the injured group but downregulated in the treated group.
Conclusion: As depicted through biochemical, histopathological and gene expression studies, Au: DOX conjugate group seems to be protective against liver fibrosis.
Cancer is a worldwide health ailment with no known boundaries in terms of mortality and occurrence rates, thus is one of the biggest threats to humankind. Hence, there is an absolute need to develop novel therapeutics to bridge the infirmities associated with chemotherapy and conventional surgical methodologies including impairment of normal tissue, compromised drug efficiency and an escalation in side effects. In lieu of this, there's been a surge in curiosity towards development of injectable hydrogels for cancer therapy because local administration of the active pharmaceutical agent offers encouraging advantages such as providing higher effective dose at target site, prolonged retention time of drug, ease of administration, mitigation of dose in vivo ,improved patient compliance. Furthermore, due to its biocompatible nature such systems can significantly reduce the side effects that occur on long-term exposure to chemotherapy. The present review details the most recent advancements in in-situ gel forming polymers (natural and synthetic), polymeric cross-linking methodologies and in-situ gelling mechanisms, focusing on their clinical benefits in cancer therapy.
Previous reviews of the works on magnetic nanoparticles for hyperthermia induced treatment concentrated mostly on magnetic fluid hyperthermia (MFH) employing monometallic/metal oxide nanocomposites. In the literature, the word "hyperthermia" was also limited to the use of heat for medicinal purposes. A number of publications have recently been published demonstrating that magnetic nanoparticle-based hyperthermia may produce restricted high temperatures, resulting in the release of medicines that are either connected to the magnetic nanoparticles or encased in polymer matrices. In this debate, we propose broadening the concept of "hyperthermia" to encompass temperature-based treatment as well as magnetically controlled medication delivery. The review also addresses core-shell magnetic nanomaterials, particularly nanoshells made by stacked assembly, for the use of hyperthermia-based treatment and precise administration of drugs. The primary objective of this review article is to demonstrate how the combination of hyperthermia-induced therapy and 'on demand' drug release models may lead to effective applications in personalized medicine.