A Brief Review Upon Recent Advancement of Drug Delivery Systems Incorporated with Nanotechnology: Modern Era Approaches

Nanotechnology is a panned engineering method for transforming particulate matter into physical state. The molecular scale having a well define range which covers from 1 nm to 100 nm that has become a game changer in drug delivery systems (DDS).^[1] The shortcomings of traditional approaches include limited solubility, rapid metabolism and non-specific adverse effects. Through the facilitation of creation of novel drug carriers that improves therapeutic efficacy and safety nanoparticles is addressing these issues. Therapeutic drugs pharmacokinetic and pharmacodynamics characteristics can be enhanced by engineering nanomaterials such as liposomes, polymeric nanoparticles, nanocrystals and dendrimers.^[2]

Some major reasons led to the need of nanotechnology in the drug delivery system can be described below: -

• Its compact size facilitates easier insertion into tissues and increased accumulation in specific regions, including tumor tissues or in the site of mechanism sites.
• The interactions between nanoparticles and mammalian cells is a popular choice for diagnostics and medical imaging purpose. It indicates the scenario of internal organs and tissues by interacting with their physiochemical properties.^[3]
• Targeting ligands can be used to functionalize nano carriers, enabling targeted distribution to particular cells or tissues.
• Due to their ability penetrate tissues and be readily absorbed by cells, nanostructures enable the effective delivery of medications to their intended locations of actions. According to reports nanostructures are 15-250 times larger than of micro particles in the 1-10 um range.^[4]

One of the field of science that is expanding the fastest and most rapidly in nanotechnology, which has seen tremendous advancements in a wide range of applications. It can be applied in the context of biomedicine evolvement, which results the procurement of techniques like tissue engineering, treatment moreover instruments enhancement in diagnostics field. The idea of nanoparticle assisted medication delivery systems for illness therapy, as well as contribution of nanotechnology in specific biological disciplines with an emphasis on medicine, selected biological fields with a focus on medicine and the concept of nanoparticle enabled drug delivery systems for disease treatment.

Objectives

These following could serve as primary mantra for integrating nanotechnology into drug delivery system: -

• To detect the improvement of drug delivery precision to targeted tissues or cells by lowering side effects and increasing efficacy.
• Evolved systems maintain therapeutic levels and minimize toxicity, they enable to controlled medication release throughout time.
• To develop nano carriers that can effectively cross the barriers such as blood-brain barriers to reach the targeted sites.
• By employing nano carriers, poorly soluble medications can become more soluble and bioavailable, improving their ability to be absorbed by body.
• To create targeted treatments based on genetic variables.
• To investigate the drug’s pharmacokinetics and pharmacodynamics.
• To enable the delivery of various medications or therapeutic agents through combination therapy, thereby promoting synergistic effects and improving treatment outcomes.
• Medication delivery systems should be equipped with imaging capabilities to enable real-time tracking of medication distribution and therapeutic response.

Nanocarriers in Drug Delivery

Drugs and genes can be delivered to specific locations within the body by means of nanocarriers, which are nanoscale delivery devices. These adaptable carriers come in the form of liposomes, nanoparticles, dendrimers and micelles with special qualities appropriate for a particular use. Drugs can be more effectively administered because nanocarriers improve the stability, solubility and bioavailability of the encapsulated medications, their controlled and focused release can be tailored minimize negative effects and maximize treatment outcomes.^[5] In cancer treatment, nanocarrier can carry chemotherapy directly to the tumor location an can minimize the harm to the surrounding healthy tissue. The utilization of nanocarrier signifies a substantial development in drug delivery technologies enabling more individualized and successful medical interventions.

• Types of Nanocarriers

Different physiochemical characteristics of nanoparticle include charged surfaces, the capacity to aggregate the potential to conjugate additional groups to the surface and controlled synthesis that makes it easier to achieve desired sizes and shapes. These characteristics of nanoparticles can be more reactive

Table 1 – Nanoparticle type, silent features, advantage and application

       
           
       
Fig- Diagram of different types of Nanoparticles.^[9]

• Functionalization of Nanocarriers

Nanocarriers are extremely small particles at the nanoscale that have become highly useful instruments in many domains, particularly bioimaging and medication delivery. The technique of functionalizing nanocarriers is essential for drug delivery systems (DDS) selectively and efficacy. Functionalization is used to optimize their performance for certain applications.^[10]

Functionalization of nanocarriers allows for the targeted and regulate release of medicines, it is essential for improving DDS. In order to enhance the interaction of nanocarriers such as liposomes, nanoparticles and dendrimers with certain biological targets, this techniques entails altering with surfaces.^[11] Researchers can connect different ligands such as peptides and antibodies, using methods like covalent bonding polymer coating, and the addition of functional groups. By guiding the medications to their intended locations, this focused method not only maximizes therapeutic efficacy but also decrease negative effects by minimizing exposure to healthy tissue.^[12] It is possible to create functionalized nanocarriers that react to particular stimuli, including PH variations which would enable controlled medication release in response to the microenvironment.^[13]

The development of intelligent, multipurpose nanocarriers is advancing research and could change personalized medicine by improving treatment efficacy and customizing it to the demands of each patient.

Targeted Drug Delivery

Targeted drug deliveries is an innovative approach that aims to deliver therapeutic agents specifically to the desired site of action while minimizing exposure to healthy tissues. This approach improves patient outcomes by enhancing therapies and lowering side effects.^[14]   Nanotechnology has greatly aided in development of targeted delivery systems by enabling the creation of sophisticated drugs carriers that can successfully navigate intricate biological settings.^[15]

• Mechanisms of Targeted Drug Delivery

The two main targeting strategies used in targeted medicine delivery mechanisms are active and passive. In order to enable selective absorption by receptor mediated endocytosis, the active target makes uses of ligand such as antibodies or peptides coupled to nanocarrier, which binds precisely to the receptor on the targeted cells. On the other hands passive targeting makes use of the increased permeability and retention (EPR) effect, which causes tumor tissue’s leaky blood channels to collect nanoparticles.^[16] Furthermore, medications can be released by stimuli responsive systems in response to particular environmental cues, including changes in temperature or PH. When combined, these processes minimize side effects and increases treatment success, especially in cancer therapy.^[17]

• Active Targeting

By employing ligands that specifically attach to target cells, active targeting in drug delivery is a complex strategy that improves the specificity and effectiveness of medical treatments. With this technique the surface of drug carriers such as liposomes or nanoparticles is modified with specialized ligands (such as peptides, antibodies or small molecules) that binds and recognize receptors that are overexpressed on sick cells, especially cancer cells.^[18] The drugs loaded carriers is swallowed by receptor mediated endocytosis after the ligand binds to its matching receptor, guaranteeing that the therapeutic agent enters the targeted cells directly. This focused technique reduces systemic exposure, which lowers the possibility of side effects, while simultaneously increasing the local concentration of the drug at the intended spot. To improve treatment efficacy, folate-conjugated nanoparticles for instance can specifically target cancer cells that overexpress folate receptors.^[19] Moreover, stimuli responsive release systems which allows medications to be delivered in reactions to particular environmental triggers like PH shifts or temperature fluctuations can be coupled with active targeting. All things considered active targeting is a major breakthrough in drug delivery technology that could lead to better treatment outcomes across a range of illness, especially in personalize medicine and oncology.^[20]

       
           
       
Fig- Mechanism of Target Delivery via Passive and Active Targeting.^[21]

• Passive Targeting

In order to improve the accumulation of therapeutic agents in particular tissues, especially cancers, passive targeting in drug delivery makes use of the inherent qualities of nanoparticles and eliminates the need for activate targeting procedures. This method is based mostly on the vasculature surrounding tumors. Poorly structured blood arteries in tumor tissue are frequently more permeable than those in healthy tissues, which facilitate the easier extravasation of nanoparticles. Furthermost, these nanoparticles are retained in tumors due to ineffective lymphatic drainage, which raise the local concentration of the medications that are administered. Nanoparticles’ biodistribution and clearance rates are greatly influenced by their size, shape and surface properties, smaller particles have a propensity to circulate in the bloodstream for longer periods of time and to infiltrate tissue more successfully.^[22] For systemic medicines, passive targeting is especially helpful since it eliminates the need for intricate changes to the drug carrier, streamlining the formulation and manufacturing procedures. Although passive targeting has the potential to greatly increase the amount of medication that accumulates in tumors, it is important to remember that this approach may not ensure selectively because it may also harm healthy tissues. Thus, formulation optimization is the main focus of ongoing research in order to optimize therapeutic effectiveness while minimizing side effects.^[23]

Controlled Released

The goal of controlled release medication delivery systems is to maximize treatment effectiveness while reducing negative effects by releasing therapeutic substances at a predefined rate. These systems decrease the frequency of dosage and increase patient compliance by preserving steady medication concentrations in the bloodstream. Materials like hydrogels, microspheres and biodegradable polymers are frequently used in techniques including diffusion, polymer breakdown and osmotic pressure.^[24] This strategy is especially helpful for long-term illness like diabetes and cancer, when stable medication dosages are essential. In spite of difficulties in formulation and variations in patient’s reactions, controlled release technologies are major development in contemporary medicine.

• Mechanism of controlled release

In drug delivery systems, regulated release mechanisms are essential for optimizing pharmacokinetics and attending targeted therapeutic effects. Diffusion is one of the main mechanisms by which drug molecules move from high concentration inside a polymer matrix to a lower concentration outside.^[25] The characteristics of the polymers, which control the rate of release such as its porosity and permeability can have an impact on this process. Another technique is polymer degradation, in which the medication is gradually released from its capsule as the polymer matrix gradually degrades over time. Biodegradable polymers which can safely disintegrate in the body and minimize the need for surgical removal, are especially well suited for this procedure. Another efficient method is osmotic pressure, which works by using osmotic gradients to control the release of medications across semi-permeable membranes.^[26]

Furthermore, several systems employ environmentally responsive mechanisms, in which the release of a drug is initiated in response to particular stimuli, such as variations in PH, temperature or the existence of particular enzymes.^[27] These cutting-edge technologies cam improve targeted delivery by releasing medications selectively at predetermined bodily locations. In general, by comprehending these mechanisms scientists may create drug delivery systems that are more efficient and can customize release profiles to suits the specific requirements of different therapeutic applications.^[28]

       
           
       
Fig- Contribution of Nanoparticle in controlled release.^[29]

• PH responsive drug delivery system

PH responsive drug delivery systems that use PH fluctuations to control the release of medicinal drugs. These systems make use of polymers that in reaction to PH changes modify their swelling or solubility.^[30] This enables tailored medication release in particular setting including the gastrointestinal tract or acidic tumor tissue. Through selective medication release in regions where PH deviates from physiological baselines, these devices maximize therapeutic benefit while reducing systemic adverse effects. This focused strategy is essential helpful for cancer treatments and other situations where accurate medication administration is essential to better patient results.^[31]

• Temperature sensitive System

Advanced controlled release methods such as temperature-sensitive drug delivery systems, adjust the release of the therapeutic agents based on the temperature variations. By utilizing thermoresponsive hydrogels or other smart polymers, these systems demonstrative notable alterations in their properties when exposed to particular thresholds.^[32] Drugs are retained in a swelled condition by the polymers at lowest temperatures by a phase shift. This method can be especially helpful in the treatment of cancer as localized heating can maximize therapy.^[33] All things considered temperature-sensitive systems provide better targeting less side effects and more control over drug release profiles all of which lead to the treatments that are ultimately more successful and complied with patients.^[34]

• Enzyme responsive system

Enzyme-responsive drug delivery system are novel forms of controlled release that release medicinal drugs when certain enzymes are activated. These systems combine medications with a polymer matrix or bind them together with linkages that are sensitive to enzymes, which are frequently connected to specific tissues or illness and releases the medicine that has been encapsulated at the intended location.^[35] This focused strategy is particularly useful in cancer therapy since drugs can be released when tumor-specific enzymes are activated. Enzyme-responsive systems offer a promising approach for optimal treatment results by increasing therapeutic efficacy and reducing side effects, while also decreasing systemic exposure and improving specificity.

Combination Therapy

Combination therapies that use DDS based on nanotechnology ae a revolutionary way to treat complex diseases, including cancer. Multiple therapeutic medicines can be delivered simultaneously by incorporating them into nanocarriers, such as liposomes, nanoparticles and dendrimers through their complimentary modes of action.^[36] This approach can greatly increase the effectiveness of treatment. Combining targeted medicines with conventional chemotherapeutics helps overcome obstacles such drug resistance and enables a more through attack on cancer cells because these carriers are nanoscale, the pharmacokinetics of the medications are improved and leading permeability and retention inside tumor tissue. This is important because it maximizes therapeutic effect while reducing systemic toxicity.^[37]   

Nanotechnology based combination therapy are being investigated more and more outside of oncology, in areas such as infectious diseases where co administration of several antimicrobial drugs can successfully address drug resistance concerns, because smaller dose of each medication can be used in medications.^[38] This novel method not only increase the effectiveness of therapies but also lowers the possibility of unfavorable side effects, but creating these sophisticated systems is not without its difficulties.

Formulating stability, biocompatibility and regulatory approval are the three areas that need to be carefully considered. In order to ensure both safety and efficacy future research will concentrate on improving these combination medicines for particular therapeutic uses.^[39] Combination medicines have the potential to completely transform treatment as we refine nanotechnology and continue to decipher the complexity of disease causes.

• Mechanism of Combination Therapy

Combination therapy works by combining many therapeutic agents in a way that maximizes overall treatment efficacy while reducing the probability of drug resistance. This strategy is based on the idea that distinct medications can target diverse disease pathways or mechanisms can target diverse disease pathways or mechanisms of actions, resulting in a more through attack on the underlying illness.^[40] In the treatment of cancer, it is possible to simultaneously interrupt cell proliferation and induce apoptosis in cancer cells by combining targeted medicines that inhibit specific growth factor receptors with chemotherapeutics that destroy DNA. Compared to the use of a single medication, this multifaceted approach makes it more difficult for tumors to develop resistance.^[41]

Combination therapy, which targets many components of the pathogen’s life cycle or mode of action functions similarly in the case of infectious disorders. Antiretroviral medications are used in combination to target multiple stages of viral replication in HIV treatment, resulting in a considerable improvement in both viral suppression and patient outcomes. Furthermore, combination therapy may enable the use of lower dosage of each medication, which lowers the risk of adverse effects and improves patient adherence.^[42] Combination therapy works by combining the advantages of advantage of different medications to create a more potent and effective treatment plan that may be tailored to the unique characteristics of different diseases and in the end improve patient outcomes.^[43]