Development of Local Drug Delivery Systems for Periodontal Disease

Periodontitis is an inflammatory disease induced by complex interactions between the host immune system and pathogens that affect the integrity of teeth-supporting tissues. To prevent disease progression and thus preserve the alveolar bone structure, simultaneous anti-inflammatory and osteogenic intervention is essential. Hence, simvastatin (SIM) and a glycogen synthase kinase 3 beta inhibitor (BIO) were selected as anti-inflammatory and osteogenic agents. First, SIM is a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia. It has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubility. To address this challenge, we proposed to design and evaluate the therapeutic efficacy of a novel simvastatin prodrug with better water solubility and bone affinity. The prodrug (SIM-PPi) was synthesized by directly conjugating a SIM trimer to a pyrophosphate (PPi). It was characterized and evaluated in vitro for its water solubility, osteotropicity, toxicity, anti-inflammatory, and osteoinductive properties. It was then tested for anti-inflammatory and osteoinductive properties in vivo by three weekly injections into gingiva of a ligature-induced experimental periodontitis rat model. In vitro studies showed that SIM-PPi has greatly improved water-solubility of SIM and shows strong binding to hydroxyapatite (HA). In macrophage culture, SIM-PPi inhibited LPS-induced pro-inflammatory cytokines (IL-1β, IL-6). In osteoblast culture, it was found to significantly increase alkaline phosphatase (ALP) activity with accelerated mineral deposition, confirming the osteogenic potential of SIM-PPi. When tested in vivo on an experimental periodontal bone-loss model, SIM-PPi exhibited a superior prophylactic effect compared to dose equivalent SIM in reducing inflammatory cells and in preserving the alveolar bone structure, as shown in the histological and micro-CT data. Second, a glycogen synthase kinase 3 beta inhibitor (BIO) is a potent inflammation modulator and osteogenic agent. However, its lack of osteotropicity, poor water solubility, and potential long-term side effects have hampered its clinical applications. To address these limitations, pyrophosphorylated Pluronic F127 was synthesized to prepare a novel, injectable and thermosensitive hydrogel (PF127) that could effectively release BIO to exert its therapeutic effects locally. Comparing to F127 hydrogel, PF127 hydrogels exhibited strong binding to hydroxyapatite (HA) discs as a function of PPi content. Additionally, BIO’s solubility in PF127 solution compared to F127 was greatly improved and proportionally to the polymer concentration. When tested in vivo on an experimental periodontal bone-loss rat model, PF127-BIO hydrogel exhibited a superior prophylactic effect in preserving alveolar bone structure and preventing periodontal inflammation, as shown by the micro-CT and histological data, respectively. Altogether, these two delivery strategies (SIM-PPi prodrug and PF127 hydrogel) with excellent bone binding may have the potential to be further developed for better clinical management of bone loss associated with periodontitis

Osmotic Pump Drug Delivery Systems—A Comprehensive Review

In the last couple of years, novel drug delivery systems (NDDS) have attracted much attention in the food and pharmaceutical industries. NDDS is a broad term that encompasses many dosage forms, one of which is osmotic pumps. Osmotic pumps are considered to be the most reliable source of controlled drug delivery, both in humans and in animals. These pumps are osmotically controlled and release active agents through osmotic pressure. To a large extent, drug release from such a system is independent of gastric fluids. Based on such unique properties and advantages, osmotic pumps have made their mark on the pharmaceutical industry. This review summarizes the available osmotic devices for implantation and osmotic tablets for oral administration

Development, Therapeutic Evaluation and Theranostic Applications of Cubosomes on Cancers: An Updated Review

Cancer is a group of disorders characterized by aberrant gene function and alterations in gene expression patterns. In 2020, it was anticipated that 19 million new cancer cases would be diagnosed globally, with around 10 million cancer deaths. Late diagnosis and interventions are the leading causes of cancer-related mortality. In addition, the absence of comprehensive cancer therapy adds to the burden. Many lyotropic non-lamellar liquid-crystalline-nanoparticle-mediated formulations have been developed in the last few decades, with promising results in drug delivery, therapeutics, and diagnostics. Cubosomes are nano-structured liquid-crystalline particles made of specific amphiphilic lipids in particular proportions. Their ability to encapsulate lipophilic, hydrophilic, and amphiphilic molecules within their structure makes them one of a kind. They are biocompatible, versatile drug carriers that can deliver medications through various routes of administration. Many preclinical studies on the use of cubosomes in cancer treatment and theranostic applications have been conducted. However, before cubosomes may be employed in clinical practice, significant technical advances must be accomplished. This review summarizes the development of cubosomes and their multifunctional role in cancer treatment based on the most recent reports.</jats:p

Novel Hydrogels for Topical Applications: An Updated Comprehensive Review Based on Source

Active pharmaceutical ingredients (API) or drugs are normally not delivered as pure chemical substances (for the prevention or the treatment of any diseases). APIs are still generally administered in prepared formulations, also known as dosage forms. Topical administration is widely used to deliver therapeutic agents locally because it is convenient and cost-effective. Since earlier civilizations, several types of topical semi-solid dosage forms have been commonly used in healthcare society to treat various skin diseases. A topical drug delivery system is designed primarily to treat local diseases by applying therapeutic agents to surface level parts of the body such as the skin, eyes, nose, and vaginal cavity. Nowadays, novel semi-solids can be used safely in pediatrics, geriatrics, and pregnant women without the possibility of causing any allergy reactions. The novel hydrogels are being used in a wide range of applications. At first, numerous hydrogel research studies were carried out by simply adding various APIs in pure form or dissolved in various solvents to the prepared hydrogel base. However, numerous research articles on novel hydrogels have been published in the last five to ten years. It is expected that novel hydrogels will be capable of controlling the APIs release pattern. Novel hydrogels are made up of novel formulations such as nanoparticles, nanoemulsions, microemulsions, liposomes, self-nano emulsifying drug delivery systems, cubosomes, and so on. This review focus on some novel formulations incorporated in the hydrogel prepared with natural and synthetic polymers.</jats:p

Development, Therapeutic Evaluation and Theranostic Applications of Cubosomes on Cancers: An Updated Review

Cancer is a group of disorders characterized by aberrant gene function and alterations in gene expression patterns. In 2020, it was anticipated that 19 million new cancer cases would be diagnosed globally, with around 10 million cancer deaths. Late diagnosis and interventions are the leading causes of cancer-related mortality. In addition, the absence of comprehensive cancer therapy adds to the burden. Many lyotropic non-lamellar liquid-crystalline-nanoparticle-mediated formulations have been developed in the last few decades, with promising results in drug delivery, therapeutics, and diagnostics. Cubosomes are nano-structured liquid-crystalline particles made of specific amphiphilic lipids in particular proportions. Their ability to encapsulate lipophilic, hydrophilic, and amphiphilic molecules within their structure makes them one of a kind. They are biocompatible, versatile drug carriers that can deliver medications through various routes of administration. Many preclinical studies on the use of cubosomes in cancer treatment and theranostic applications have been conducted. However, before cubosomes may be employed in clinical practice, significant technical advances must be accomplished. This review summarizes the development of cubosomes and their multifunctional role in cancer treatment based on the most recent reports

Novel Hydrogels for Topical Applications: An Updated Comprehensive Review Based on Source

Active pharmaceutical ingredients (API) or drugs are normally not delivered as pure chemical substances (for the prevention or the treatment of any diseases). APIs are still generally administered in prepared formulations, also known as dosage forms. Topical administration is widely used to deliver therapeutic agents locally because it is convenient and cost-effective. Since earlier civilizations, several types of topical semi-solid dosage forms have been commonly used in healthcare society to treat various skin diseases. A topical drug delivery system is designed primarily to treat local diseases by applying therapeutic agents to surface level parts of the body such as the skin, eyes, nose, and vaginal cavity. Nowadays, novel semi-solids can be used safely in pediatrics, geriatrics, and pregnant women without the possibility of causing any allergy reactions. The novel hydrogels are being used in a wide range of applications. At first, numerous hydrogel research studies were carried out by simply adding various APIs in pure form or dissolved in various solvents to the prepared hydrogel base. However, numerous research articles on novel hydrogels have been published in the last five to ten years. It is expected that novel hydrogels will be capable of controlling the APIs release pattern. Novel hydrogels are made up of novel formulations such as nanoparticles, nanoemulsions, microemulsions, liposomes, self-nano emulsifying drug delivery systems, cubosomes, and so on. This review focus on some novel formulations incorporated in the hydrogel prepared with natural and synthetic polymers

Polymeric Lipid Hybrid Nanoparticles (PLNs) as Emerging Drug Delivery Platform—A Comprehensive Review of Their Properties, Preparation Methods, and Therapeutic Applications

Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric kernel and lipid/lipid–PEG shells that have the physical stability and biocompatibility of both polymeric nanoparticles and liposomes. PLNs have emerged as a highly potent and promising nanocarrier for a variety of biomedical uses, including drug delivery and biomedical imaging, owing to recent developments in nanomedicine. In contrast with other forms of drug delivery systems, PLNs have been regarded as seamless and stable because they are simple to prepare and exhibit excellent stability. Natural, semi-synthetic, and synthetic polymers have been used to make these nanocarriers. Due to their small scale, PLNs can be used in a number of applications, including anticancer therapy, gene delivery, vaccine delivery, and bioimaging. These nanoparticles are also self-assembled in a reproducible and predictable manner using a single or two-step nanoprecipitation process, making them significantly scalable. All of these positive attributes therefore make PLNs an attractive nanocarrier to study. This review delves into the fundamentals and applications of PLNs as well as their formulation parameters, several drug delivery strategies, and recent advancements in clinical trials, giving a comprehensive insight into the pharmacokinetic and biopharmaceutical aspects of these hybrid nanoparticles

Nanostructured lipid carrier system: A compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery

Abstract The lipid-based colloidal carriers, such as nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), nanocapsules, liposomes, and microemulsion, are the latest and significant entrants in the development of drug delivery systems owing to their myriad advantages. The NLCs are second-generation SLNs having unstructured matrix, have high drug loading, and provide long-term drug stability in comparison to SLNs and other colloidal systems, which show lower drug loading and experience burst release/drug expulsion during storage. This review is aimed to summarize the formulation development and optimization strategies for NLCs as reported in the literature collected from authentic databases. Various types of NLCs, formulation components, methods of preparation, characterization parameters, optimization (statistical designs) strategies, toxicity, regulatory aspects, and their applications in oral, parenteral, ocular, pulmonary, nose-to-brain, tumor targeting, and transdermal drug delivery have been dealt in detail. Patents granted on the NLCs have also been enlisted.</jats:p

Polymeric Lipid Hybrid Nanoparticles (PLNs) as Emerging Drug Delivery Platform—A Comprehensive Review of Their Properties, Preparation Methods, and Therapeutic Applications

Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric kernel and lipid/lipid–PEG shells that have the physical stability and biocompatibility of both polymeric nanoparticles and liposomes. PLNs have emerged as a highly potent and promising nanocarrier for a variety of biomedical uses, including drug delivery and biomedical imaging, owing to recent developments in nanomedicine. In contrast with other forms of drug delivery systems, PLNs have been regarded as seamless and stable because they are simple to prepare and exhibit excellent stability. Natural, semi-synthetic, and synthetic polymers have been used to make these nanocarriers. Due to their small scale, PLNs can be used in a number of applications, including anticancer therapy, gene delivery, vaccine delivery, and bioimaging. These nanoparticles are also self-assembled in a reproducible and predictable manner using a single or two-step nanoprecipitation process, making them significantly scalable. All of these positive attributes therefore make PLNs an attractive nanocarrier to study. This review delves into the fundamentals and applications of PLNs as well as their formulation parameters, several drug delivery strategies, and recent advancements in clinical trials, giving a comprehensive insight into the pharmacokinetic and biopharmaceutical aspects of these hybrid nanoparticles.</jats:p