Abstract

The development of novel drug delivery systems (NDDS) has revolutionized the pharmaceutical industry by enhancing therapeutic efficacy, reducing side effects, and improving patient compliance. This thesis provides an overview of NDDS, classifying them into targeted, controlled, and modulated release systems. The significance of polymers in NDDS is highlighted, with a focus on natural, synthetic, biodegradable, conducting, and smart polymers. The advantages of NDDS, including increased bioavailability, reduced toxicity, and improved patient outcomes, are discussed. The thesis also explores various applications of NDDS, such as cancer therapy, tissue engineering, and gene delivery. Furthermore, the limitations and challenges associated with NDDS are addressed, emphasizing the need for continued research and development. This study contributes to the understanding of NDDS and their potential to transform the field of pharmaceuticals.

Keywords

Introduction

Table:1

Classification of Novel Drug Delivery Systems:  

       
           
       
Figure.3:  Examples of natural polymers

Types of Natural Polymers:  

       
           
       
Figure 5:Examples of biodegradable polymers

       
           
       
Figure 6:Schematic Representation of Reservoir and Monolithic drug delivery system

       
           
       
Figure:7 Comparison of drug release mechanism in Reservoir and Monolithic drug delivery system

Table :2

3. Release Controlled by Erosion:   

Drug release in erosion-based systems occurs when the polymeric carrier erodes or breaks down. This process is especially crucial in biodegradable systems because the matrix breaks down gradually as a result of external variables like pH or enzymatic activity.  

Bulk Erosion: 

Drug release results from the uniform degradation of the whole polymer matrix in bulk-eroding systems. Surface Erosion: 

 From the outside inward, surface-eroding systems deteriorate layer by layer. The rate at which drugs release is directly correlated with the polymer's rate of erosion. 

4.Osmotically Controlled Release:  

Drug release is governed by osmotic pressure in osmotically controlled systems. Osmotic pressure is created in these systems when water passes through a semi-permeable membrane and into the drug delivery device. The drug solution is forced through a tiny opening at a predetermined pace by this pressure.  

A steady, zero-order release is produced by osmotic pumps, which means that the drug is released gradually and at a constant rate regardless of the surrounding conditions.  

5. Swelling-Controlled Release:  

Systems that use this technique make use of hydrophilic polymers, which draw in water and cause the matrix to swell. The swelling of the polymer results in an increase in its permeability or the creation of channels that allow the drug to diffuse. Hydrogels, whose swelling kinetics can be precisely controlled to control drug release, are frequently found to exhibit swelling-controlled release. 

6. Release Sensitive to pH:   

Changes in the pH environment cause the release of drugs in pH-sensitive drug delivery systems. These systems are made of polymers that, depending on the pH, either dissolve or swell. For instance, a medication intended for intestinal release could be enclosed in a polymer that solidifies in the stomach's acidic environment but dissolves in the intestines' basic pH.  

7. Targeted Release (Ligand-Mediated):  

Drugs can be delivered to particular tissues or cells using targeted delivery methods, which lowers systemic side effects and increases therapeutic efficacy. These systems are frequently designed to bind to particular receptors on the target cells using targeting ligands, which can be small molecules, peptides, or antibodies. 

The drug is released from the target site once the drug delivery system binds to it, either by endocytosis or through other mechanisms that are triggered by the binding. 

8. Stimuli-Responsive Release:  

 Drug delivery systems with this feature are made to release the medication in response to certain outside stimuli, like light, magnetic fields, temperature, or ultrasound.  

Systems that respond to temperature: These systems release the medication when exposed to specific temperatures. Temperature variations may cause the polymer matrix to expand or contract, releasing the medication.  

Systems that react to light: These systems release the medication in response to certain light wavelengths. Drug release occurs as a result of a chemical or physical change in the matrix brought on by the light.  Magnetically triggered systems: The drug delivery system contains magnetic nanoparticles that are triggered by an external magnetic field.  

9. Ion-Exchange Controlled Release:  

 In ion-exchange systems, the drug-loaded polymer and the surrounding biological fluids exchange ions, which controls the release of the drug. A controlled release of the medication occurs when counter-ions in the bodily fluid displace the drug, which is bound to an ion-exchange resin.  

10. Release Triggered by Ultrasound:   

In drug delivery systems, ultrasound waves can cause mechanical vibrations or heating that can lead to the drug carrier breaking down or the matrix becoming more permeable. This makes it easier for the medication to release in response to ultrasonic exposure, allowing it to target particular tissues or regions.  

List of drug carrier in NDDS:                                                          

Pytosomes                                                                                                                                                       liposomes                                                                                                                                                        Nanoparticals                                                                                                                                                 

Emulsions                                                                                                                                                      

Microsphere                                                                                                                                                   

Ethosomes                                                                                                                                                      

Solid lipid particles                                                                                                                                        

Niosomes                                                                                                                                                       

Proniosomes                                                                                                                                                   

Dendrimers                                                                                                                                                   

Liquid crystals                                                                                                                                               

Hydrogels                     

Phytosome:   

Phytosomes are lipid-compatible molecular complexes made up of the terms "some," which denotes cell-like, and "phyto," which means plant. The molar ratio of polyphenolic phytoconstituents and phosphatidyl choline can be complexed to create a novel herbal drug delivery system called a "Phytosome." Phytosomes are enhanced herbal products that are more effectively absorbed and used to achieve superior outcomes compared to traditional herbal extracts. The pharmacokinetic and therapeutic profiles of phytosomes are superior to traditional herbal extracts. 

Benefits of phytosome:   

Because phytosome enhances the absorption of active ingredients, a small dose is needed to achieve the desired effects. 

There is a noticeable improvement in bile's solubility and drug entrapment with herbal constituents, and it can specifically target the liver.  

Phytosome exhibits good stability because it forms chemical bonds between phosphatidylcholine molecules. 

The percutaneous absorption of herbal phytoconstituents is enhanced by phytosomes.[13]   

Liposomes:    

Liposomes are vesicles made of many, few, or just one phospholipid bilayer; the polar character of the liposomal core allows polar drug molecules to be encapsulated; amphiphilic and lipophilic molecules are solubilised within phospholipid bilayer according to their affinity towards phospholipids. Liposomes are used against infectious diseases and can deliver certain vaccines. During cancer treatment they encapsulate drugs, shielding healthy cells from their toxicity and preventing their concentration in vulnerable tissues like those of patient kidneys and livers. Liposomes can also reduce or eliminate certain common side effects of cancer treatment such as nausea and hair loss. 

Benefits: By altering the surface with ligands or antibodies, liposomes improve the solubility of poorly soluble drugs, lower drug toxicity, and enable targeted delivery.

Applications:   

Liposomal formulations find use in vaccinations, antifungal therapies, and cancer therapy (such as Doxil® for the delivery of doxorubicin).  Challenges include high production costs, rapid clearance from the bloodstream by the reticuloendothelial system (RES), and stability issues.

Use of Liposomes:  

By using liposomes to transport the drugs to the site of action, innovative drug delivery systems have made a significant and noteworthy advancement. Both modified and unmodified liposomes have the power to alter the pharmacokinetic parameters of the drugs. These are frequently employed to prevent adverse effects like myelosuppression and to deliver cytotoxic agents to the tumour tissue. They are also employed in receptormediated endocytosis targeting. The ability to target different medications to organs such as the heart, liver, kidney, lungs, and bones is another huge use for modified liposomes.[14]

Nanoparticles:   

Nanoparticles, which can be either amorphous or crystalline, are solid particles that include nanospheres and nanocapsules with sizes ranging from 10 to 200 nm. They can encapsulate and/or adsorb a medication, shielding it from enzymatic and chemical deterioration. Biodegradable polymeric nanoparticles have garnered significant interest as possible drug delivery agents in recent times due to their potential uses in controlled drug release, targeting specific organs or tissues, acting as DNA carriers in gene therapy, and delivering proteins, peptides, and genes orally. [15]

Uses:   

1. Cancer treatment.  
2. Genetic modification.  
3. Delivery of vaccines.  
4. Disorders of the nervous system.  
5. Diagnostics and imaging.  

Benefits of the delivery system for nanoparticles   

1. The herbal formulation is delivered straight to the site of action by the nanoparticulate system.  
2. A higher therapeutic index and efficacy.  
3. More stability through encapsulation  
4. Enhanced impact of pharmacokinetics 

5.Producible in a range of sizes and with complex surface characteristics. 

Emulsions:   

Emulsion is a biphasic system in which minute droplets with diameters ranging from 0.1 ?m to 100 ?m are intimately distributed throughout the other phase. An emulsion always consists of two phases: an oily liquid, or non-aqueous phase, and water, or the aqueous phase.  

Among these, the sub-micro-emulsion is referred to as liquid emulsion, and the microemulsion is also known as nano emulsion. Microemulsions are transparent, thermodynamically stable substances that are often combined with co-surfactants. 

Benefits of formulation based on emulsions:   

1. Because it is packed in the inner phase and makes direct, the drug can be released for an extended period of time.  
2. Interaction with other tissues and the body.  

3.When the lipophilic medications are formulated into an o/w/o emulsion, the oil droplets are phagocytosed by macrophages, which raises the concentration of the drug in the kidney, spleen, and liver.  

4.The emulsion's herbal formulation will strengthen the hydrolysed formulated material's stability and enhance the drug's absorption into the skin and mucous membranes.  

5.The novel kind, namely elemenum emulsion, is safe and effective as an anti-cancer medication to the liver and heart.[16]  

Microsphere:  

Small spherical particles, typically ranging in diameter from 1 ?m to 1000 ?m (1 mm), make up a microsphere. Micro-particles are another name for microspheres. A wide range of synthetic and natural materials can be used to create microspheres. Commercially available microspheres include glass, polymer, and ceramic materials. There are two types of microspheres: biodegradable and non-biodegradable. Albumin microspheres, modified starch microspheres, gelatin microspheres, polypropylene dextran microspheres, polylactic acid microspheres, and so on are examples of biodegradable microspheres. As per the extant literature reports on non-biodegradable microspheres, the only polymer that has been authorised for human use is polylactic acid, which is utilised as a controlled-release agent. Since the densities of solid and hollow microspheres differ greatly, they have different uses.

Uses:   

1. Cancer treatment.  
2. Delivery of vaccines.  
3. Hormone substitute medication.  

4.Pain management.  

5. Delivery to the eyes.  

Ethosomes:   

A combination of phospholipids and a high ethanol concentration forms ethosomes. Because this carrier can deeply penetrate the skin, medication delivery to the skin's deeper layers and blood circulation can both be improved. These formulations are helpful for delivering alkaloids topically to patients in the comforting forms of gel and cream. Due to the skin's lipid domain becoming more fluid, they exhibit an increase in permeability through the skin. The tropical delivery of ethosomes has limitations due to its unstable nature and low skin penetration. Tetrandine's topical absorption through dermal delivery was tested using ethosomes, and the relationship between formulations and the pharmacological activity of Tetrandine loaded in the formulation was also investigated obtained. Tetrandrine-loaded ethosomes were topically applied to rats, but the drug level was too low to be detected in the rat plasma, according to the results of the drug levels in the plasma. Consequently, ethosomes were shown to be a promising carrier for enhancing tetrandine topical delivery via skin.          

Benefits of ethosomes:  

1. Ethosomes improve a drug's transdermal skin penetration.  
2. The delivery of numerous different types of medications in large quantities is made possible by etheromes. 3. Patients' compliance improves when the ethosomal medication is given in semisolid form.[17]   

Solid lipid nanoparticles:   

(SLNs) represent a novel approach to pharmaceutical formulation or delivery. For the delivery of medications to intestinal lymphatics, conventional methods including surface modification, prodrug synthesis, complex formation, and the use of permeability enhancers have been developed. In addition, a number of potential carriers for oral intestinal lymphatic delivery have been explored, including polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions, micellar solutions, and most recently, solid lipid nanoparticles (SLN).  

An average solid lipid nanoparticle's diameter ranges from 10 to 1000 nanometres, making it spherical in shape. Lipophilic molecules can be dissolved by the solid lipid core matrix found in solid lipid nanoparticles. Emulsifiers, or surfactants, stabilise the lipid core. Triglycerides (like tristearin), diglycerides (like glycerol bahenate), monoglycerides (like glycerol monostearate), fatty acids (like stearic acid), steroids (like cholesterol), and waxes (like acetyl palmitate) are all included in the broader definition of "lipid" used here. To stabilise the lipid dispersion, emulsifiers of all classes (in terms of charge and molecular weight) have been employed. Emulsifier combinations have been found to have a potentially more effective effect on preventing particle agglomeration.[18]  

Niosomes:    

Multilamellar vesicles called niosomes are created when cholesterol and non-ionic surfactants of the alkyl or dialkyl poly-glycerol ether class combine. Previous research conducted in collaboration with L'Oreal has demonstrated that niosomes share many characteristics with liposomes when it comes to their potential as drug carriers. Niosomes differ from liposomes in that they have a few benefits over the latter.[19] 

Proniosomes:   

Proniosomes gel is an advancement over noisome and has a multitude of uses in the delivery of active ingredients to desired locations. Gels containing proniosomes are those that, when hydrated in situ with skin moisture, transform into niosomes. 

Dendrimers:   

Dendrimers are well-defined, man-made nanoparticles with a diameter of roughly 5–10 nm. They consist of a control core surrounded by polymer layers. The surface of dendrimers has a variety of locations where drugs can be attached, as well as places where materials like PEG can be attached to change the way dendrimers interact with the body. Dendrimers can have PEG attached to them in order to "disguise" them and hinder the body's defence mechanism from identifying them, which will slow down the breakdown process. This intriguing particle has great potential for treating cancer. Other molecules can readily cling to its surface thanks to its numerous branches.  

Dendrimers have been engineered by researchers into complex anticancer machines that carry five chemical tools: a molecule that binds to cancer cells; a second that fluoresces when it detects genetic mutations; a third that helps with x-ray tumour shape imaging; a fourth that carries drugs that are released when needed; and a fifth that would signal the death of cancerous cells. The inventors of these dendrimers tested them successfully on cancer cells in culture and soon hope to test them on live animals.  

Liquid Crystals:    

The characteristics of both liquid and solid states are combined in liquid crystals. They can have various geometries and alternative polar and nonpolar layers (a lamellar phase) that allow the inclusion of aqueous medication solutions. 

Hydrogels:                

Hydrogels are three-dimensional, hydrophilic polymeric networks that can absorb a lot of water or biological fluids. They function as carriers in swellable and swelling-controlled release systems or as regulators of drug release in reservoir-based controlled release systems.[20] 

NOVEL DRUG DELIVERY SYSTEM FOR  

DIABETES MANAGEMENT   

Recent developments in drug delivery systems, such as oral, inhalable, and transdermal techniques, as well as the use of nanotechnology and glucoseresponsive smart systems in diabetes treatment, is given in this article. 

1.Oral Insulin Delivery Systems:   

Because it is non-invasive and can mimic the physiological pathway of endogenous insulin secretion, oral insulin administration is regarded as the "holy grail" of diabetes treatment. The main problems with oral insulin are low intestinal epithelium permeability and its breakdown by digestive enzymes in the gastrointestinal tract. 

Current Developments:  

 1. Oramed Pharmaceuticals has made significant strides with their oral insulin capsule, which uses a protective coating to prevent degradation in the stomach and an absorption enhancer to facilitate insulin uptake in the small intestine. 

2.Novo Nordisk (NN1953/OI338GT): 

Novo Nordisk is a leader in insulin therapies and has been working on oral insulin formulations for many years. OI338GT is one of their investigational products. The drug aims to protect insulin from stomach acid and deliver it effectively into the bloodstream. However, none of their oral insulin formulations have yet reached the market. 

3. Biocon: 

Biocon is working on oral insulin formulations, including a tablet form of insulin, but their product has not yet reached the market. They are in collaboration with partners and are conducting clinical trials. 

4. Capsulin by Diabetology Ltd.: 

Diabetology is another company exploring oral insulin, with their product Capsulin. They are developing oral insulin using a proprietary gel capsule that protects insulin through the digestive system. Though Capsulin has shown promise in early trials, it is still not available commercially.  Biotechnological Approaches: Encasing nanoparticles and using polymeric systems to shield insulin molecules from deterioration have demonstrated encouraging outcomes. 

Clinical Implications: By reducing the need for injections, oral insulin can increase patient compliance. The long-term safety and effectiveness of these systems are being evaluated in ongoing clinical trials.[21] 

 2. Systems for Transdermal Drug Delivery:   

Transdermal patches present a novel, non-invasive insulin delivery option. They can do away with the requirement for numerous daily injections and are made to deliver regulated insulin release over an extended period of time. 

Microneedle Patches: These devices use tiny needles to gently pierce the skin and administer insulin or other diabetic drugs. One such example that is being developed is the microneedle patch from Zosano Pharma.  Benefits: The ease of use of these patches increases patient adherence, and they may lead to more reliable glucose control. 

Challenges: Concerns about skin irritation, variations in absorption rates according to skin type, and the necessity of additional research on longterm use still need to be addressed.[22]  3. Inhalable Insulin Delivery:  

 This non-invasive technique provides quick insulin delivery to the lungs. 

One well-known FDA-approved product is MannKind Corporation's

Afrezza, which delivers fast-acting insulin absorbed through pulmonary tissues.  

Mechanism of Action: Compared to subcutaneous insulin, Afrezza's action begins sooner because it is delivered through an inhaler device that absorbs insulin in the alveoli.  

Clinical Benefits: Inhalable insulin provides faster glycaemic control, making it especially helpful for controlling blood sugar levels after meals. Also, by removing the discomfort associated with injections, it enhances the quality of life for patients. 

Limitations: Compared to injectable forms, inhalable insulin has a lower bioavailability and is not recommended for patients with respiratory conditions like COPD or asthma.[23]  

4. The Use of Nanotechnology in the Delivery of Diabetes  

Medications: Using nanoparticles, diabetes medications can be delivered with better targeting, increased stability, and controlled release. These devices can be programmed to release insulin or other medications that control blood sugar in response to physiological cues like blood sugar levels.  

Oral Insulin Based on Nanoparticles: By using nanocarriers, such as liposomes or PLGA (polylactic-co-glycolic acid) nanoparticles, insulin can be protected from GI tract degradation and absorbed more easily.  Combination Therapies: Insulin and GLP-1 agonists can be co-delivered by nanoparticles, enabling more thorough control of glucose levels and insulin resistance.  

Future Directions: By enabling targeted and controlled drug release, nanoparticle-based delivery systems present a promising avenue for personalised diabetes treatment. Refining these systems to increase bioavailability and decrease side effects is the main focus of current research.[24] 

5. Intelligent Medication Administration Systems:   

Intelligent medication delivery systems are starting to emerge as a groundbreaking method of managing diabetes. In order to replicate the body's natural regulation of insulin, these systems use stimuli-responsive materials to release insulin in response to changes in blood glucose levels.  Glucose-Responsive Systems: Providing a closed-loop insulin delivery system, glucose-responsive hydrogels, nanoparticles, and microneedles can release insulin when blood sugar levels rise. Smart Insulin Patch: Based on glucose concentrations in the interstitial fluid of the skin, Zhen Gu's lab has created a smart insulin patch that releases insulin through the use of microneedles.  

Benefits: These systems are a major advancement in the treatment of diabetes because they offer more accurate glucose control, lower the risk of hypoglycemia, and require fewer dosing interventions.[25] 

6. Artificial Pancreas with Closed-Loop Insulin Delivery Systems:  

The creation of the artificial pancreas, which combines insulin pumps and continuous glucose monitoring, is a major advancement in the treatment of diabetes. One of the first hybrid closed-loop systems to receive FDA approval is Medtronic's MiniMed 670G system, which automatically modifies insulin delivery in response to real-time glucose readings. 

Benefits: By lessening the burden of managing diabetes on a daily basis, these systems enhance glycaemic control and lower the risk of complications related to diabetes.  challenges: Present barriers to widespread adoption include high costs and the requirement for additional algorithmic accuracy and reliability tuning.[26]  

CONCLUSION:

In conclusion, the exploration of Novel Drug Delivery Systems (NDDS) highlights significant advancements in the pharmaceutical field that enhance drug efficacy, reduce side effects, and improve patient compliance. These systems, which include targeted, controlled, and modulated release mechanisms, offer innovative solutions that address limitations of conventional drug delivery. The application of natural, synthetic, and biodegradable polymers plays a critical role in optimizing drug release, targeting, and therapeutic outcomes. While NDDS offer considerable benefits, challenges such as formulation complexity and regulatory hurdles underscore the need for ongoing research and development. By advancing these systems, the potential to transform treatment modalities and patient care continues to grow, positioning NDDS as a cornerstone of modern and future pharmaceutical innovations

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